1. An image taking apparatus, comprising:
a solid-state image sensor; and
a taking lens including a lens barrel that houses a lens disposed in front of the solid-state image sensor,
wherein a shielding member that blocks an electromagnetic wave radiated from a front surface of the solid-state image sensor is provided on an outer circumference of the lens barrel, and
a metallic member electrically floating in the lens barrel is grounded, wherein the taking lens is connected to a flexible wiring board and has a driving device that drives an optical member in the taking lens, and
the flexible wiring board is laid along the shielding member in such a manner that a length of a part of the flexible wiring board between the driving device and the shielding member is minimized.
2. The image taking apparatus according to claim 1, wherein the driving device includes two or more of a shutter actuator, a diaphragm actuator, a camera-shake correcting actuator and a focusing actuator, and the two or more actuators are placed at different circumferential positions in the taking lens.
3. An image taking apparatus, comprising:
a solid-state image sensor; and
a taking lens including a lens barrel that houses a lens disposed in front of the solid-state image sensor,
wherein a shielding member that blocks an electromagnetic wave radiated from a front surface of the solid-state image sensor is provided on an outer circumference of the lens barrel, and
a metallic member electrically floating in the lens barrel is grounded,
wherein the shielding member covers the outer circumference of the lens barrel and the front surface of the lens barrel except for an opening of the lens barrel, and
further comprising a shielding plate that covers the front surface of the solid-state image sensor except for a light-receiving area thereof,
wherein the shielding plate blocks an electromagnetic wave radiated from the front surface of the solid-state image sensor except for the light-receiving area,
wherein the taking lens is a rear focus type zoom lens including a first lens group for changing magnification and a second lens group disposed in the rear of the first lens group for performing correction and focusing when changing magnification, and
the lens barrel is a focus lens guide sleeve that houses the second lens group, and
wherein the metallic member is a guide shaft for a focus lens that moves in the focus lens guide sleeve, wherein the taking lens is connected to a flexible wiring board and has a driving device that drives an optical member in the taking lens,
the flexible wiring board is laid along the shielding member in such a manner that a length of a part of the flexible wiring board between the driving device and the shielding member is minimized.
4. The image taking apparatus according to claim 3, wherein the driving device includes two or more of a shutter actuator, a diaphragm actuator, a camera-shake correcting actuator and a focusing actuator, and the two or more actuators are placed at different circumferential positions in the taking lens.
5. An image taking apparatus, comprising:
a solid-state image sensor; and
a taking lens including a lens barrel that houses a lens disposed in front of the solid-state image sensor,
wherein a shielding member that blocks an electromagnetic wave radiated from a front surface of the solid-state image sensor is provided on an outer circumference of the lens barrel, and
a metallic member electrically floating in the lens barrel is grounded,
wherein the shielding member covers the outer circumference of the lens barrel and the front surface of the lens barrel except for an opening of the lens barrel,
further comprising a shielding plate that covers the front surface of the solid-state image sensor except for a light-receiving area thereof,
wherein the shielding plate blocks an electromagnetic wave radiated from the front surface of the solid-state image sensor except for the light-receiving area,
wherein the taking lens is a rear focus type zoom lens including a first lens group for changing magnification and a second lens group disposed in the rear of the first lens group for performing correction and focusing when changing magnification, and
the lens barrel is a focus lens guide sleeve that houses the second lens group,
wherein the metallic member is a guide shaft for a focus lens that moves in the focus lens guide sleeve, and one end of the guide shaft is in contact with the shielding plate and thereby grounded,
wherein the taking lens is connected to a flexible wiring board and has a driving device that drives an optical member in the taking lens, and
the flexible wiring board is laid along the shielding member in such a manner that the length of the part of the flexible wiring board between the driving device and the shielding member is minimized.
6. The image taking apparatus according to claim 5, wherein the driving device includes two or more of a shutter actuator, a diaphragm actuator, a camera-shake correcting actuator and a focusing actuator, and the two or more actuators are placed at different circumferential positions in the taking lens.
The claims below are in addition to those above.
All refrences to claim(s) which appear below refer to the numbering after this setence.
1. A process for the manufacture of an enantiomerically enriched or pure compound of formula I:
wherein
Ra denotes Hal, cyano, COOH, COOA, A, CF3;
R1 denotes H, A, Ar, Het, Hal, \u2014(CY2)n\u2014SA, \u2014(CY2)n\u2014SCF3, \u2014(CY2)n\u2014SCN, \u2014(CY2)n\u2014CF3, \u2014(CY2)n\u2014OCF3, R, cycloalkyl, \u2014SCH3, \u2014SCN, \u2014CF3, \u2014OCF3, \u2014OA, \u2014(CY2)n\u2014OH, \u2014(CY2)n\u2014CO2R, \u2014(CY2)n\u2014CN, \u2014(CY2)n-Hal, \u2014(CY2)n\u2014NR2, (CY2)n\u2014OA, (CY2)n\u2014OCOA, \u2014SCF3, (CY2)n\u2014CONR2, \u2014(CY2)n\u2014NHCOA, \u2014(CY2)n\u2014NHSO2A, SF5, Si(CH3)3, CO\u2014(CY2)n\u2014CH3, \u2014(CY2)n\u2014N-Pyrrolidone, (CH2)nNRCOOR, NRCOOR, NCO, (CH2)nCOOR, NCOOR, (CH2)nOH, NR(CH2)nNR2, C(OH)R2, NR(CH2)nOR, NCOR, (CH2)nAr, (CH2)nHet, (CH2)nR, (CH2)nX(CH2)nAr, (CH2)nX(CH2)nHet, (CH2)nCONR2, XCONR(CH2)nNR2, N(CH2)nXCOORCO(CH2)nAr, N(CH2)nXRCO(CH2)nAr, N(CH2)nXRCO(CH2)nXAr, N(CH2)nXRSO2(CH2)nAr, N(CH2)nNRCOORCO(CH2)nAr, N(CH2)nNR2CO(CH2)nAr, N(CH2)nNR2CO(CH2)nNRAr, N(CH2)nNR2SO2(CH2)nAr, N(CH2)nXRCO(CH2)nHet, N(CH2)nXRCO(CH2)nXHet, N(CH2)nXRSO2(CH2)nHet, N(CH2)nNRCOORCO(CH2)nHet, N(CH2)nNR2CO(CH2)nHet, N(CH2)nNR2CO(CH2)nNRHet;
R2, R3 denotes H, A, Hal, OA, OR;
Y denotes H, A, Hal, OR;
A denotes Alkyl or Cycloalkyl, wherein one or more H-atoms can be replaced by Hal;
Hal denotes F, Cl, Br or I;
R denotes H or A, in the case of geminal groups R together also \u2014(CH2)5\u2014, \u2014(CH2)4\u2014 or \u2014(CH2)n\u2014X\u2014(CH2)n, or \u2014(CH2)n\u2014Z\u2014(CH2)n;
X denotes O, S, NA or NH;
Q denotes CH2\u2014NH-A, CH2\u2014NH\u2014C(O)R1, CH2\u2014NH\u2014SO2R1;
Z denotes CH2, X, CHCONH2, CH(CH2)nNRCOOR, CHNRCOOR, NCHO, CHCON(R)2, CH(CH2)nCOOR, NCOOR, CH(CH2)nOH, N(CH2)nOH, CHNH2, CH(CH2)nNR2, CH(CH2)nNR2, C(OH)R, CHNCOR, NCOR, N(CH2)nAr, N(CH2)nHet, CHR, NR, CH(CH2)nAr, CH(CH2)nHet, CH(CH2)nR, N(CH2)nCOOR, CH(CH2)nX(CH2)nAr, CH(CH2)nX(CH2)nHet, N(CH2)nCON(R)2, NSO2R, CHSO2N(R)2, XCONR(CH2)nN(R)2, NCO(CH2)nAr, NCO(CH2)nXAr, NSO2(CH2)nAr, NCO(CH2)nAr, NCO(CH2)nNRAr, NCO(CH2)nHet, NCO(CH2)nXHet, NSO2(CH2)nHet, NCO(CH2)nNRHet, N(CH2)nNR2CH, CHO(CH2)nN(R)2, CHX(CH2)nN(R)2, or, NCO(CH2)nNR2;
R6 denotes unsubstituted Ar or Het which is substituted in at least one position by Hal, NO2, CN, OR, A, \u2014(CY2)n\u2014OR, \u2014OCOR, \u2014(CY2)n\u2014CO2R, \u2014(CY2)n\u2014CN, \u2014NCOR, \u2014COR or \u2014(CY2)n\u2014NR2 or by Ar or Het which also may be substituted by Hal, NO2, CN, A, OR, OCOR, COR, NR2, CF3, OCF3, OCH(CF3)2,
R7 denotes (C\u2550O)\u2014R, (C\u2550O)\u2014NR2, (C\u2550O)\u2014OR, H or A;
Ar denotes a monocyclic or bicyclic, saturated, unsaturated or aromatic carbocyclic ring having 6 to 14 carbon atoms which may be unsubstituted which is substituted in at least one position by Hal, NO2, CN, OR, A, \u2014(CY2)n\u2014OR, \u2014OCOR, \u2014(CY2)n\u2014CO2R, \u2014(CY2)n\u2014CN, \u2014NCOR, \u2014COR or \u2014(CY2)n\u2014NR2 or by Hal, NO2, CN, A, OR, OCOR, COR, NR2, CF3, OCF3, OCH(CF3)2;
Het denotes a monocyclic or bicyclic, saturated, unsaturated or aromatic heterocyclic ring having 1 to 4 N, O andor S atoms which may be unsubstituted or which is substituted in at least one position by Hal, NO2, CN, OR, A, \u2014(CY2)n\u2014OR, \u2014OCOR, \u2014(CY2)nCO2R, \u2014(CY2)n\u2014CN, \u2014NCOR, \u2014COR or \u2014(CY2)n\u2014NR2 or by Hal, NO2, CN, A, OR, OCOR, COR, NR2, CF3, OCF3, OCH(CF3)2;
n denotes 0, 1, 2, 3, 4, 5, 6 or 7;
or a pharmaceutically acceptable tautomer or salt thereof, said process comprising:
reacting an aniline compound A and an aldehyde B
with a chiral dihydropyran methylamine compound C
in the presence of a suitable solvent and a protonic acid or Lewis acid wherein R1 to R6 and Q are as described above.
2. The process according to claim 1, wherein Q is \u2014CH2\u2014NH(CO)R, \u2014CH2\u2014NHSO2R or CH2NH-A.
3. The process according to claim 1, wherein Q is CH2NH\u2014CH3, CH2NH\u2014C(O)NH(CH2)2N(CH3)2.
4. The process according to claim 1, wherein R6 is an unsubstituted Ar.
5. The process according to claim 1, wherein R3 is H.
6. The process according to claim 1, wherein R2 is H.
7. The process according to claim 1, wherein Ra is A.
8. The process according to claim 1, wherein Ra is CF3 and R7 is H.
9. The process according to claim 1, wherein the protonic acid is trifluoroacetic acid.
10. The process according to claim 9, wherein the solvent is acetonitrile.
11. The process according to claim 1, wherein Q is \u2014CH2\u2014NHCH3, Ra is Cl, R2 is F, R3 is H, R7 is H and R6 is unsubstituted Ar.
12. A process for the manufacture of enantiomerically enriched or pure compounds of formula C:
wherein
Q denotes CH2\u2014NH-A, CH2\u2014NH\u2014C(O)R1, CH2\u2014NH\u2014SO2R1,
R1 denotes H, A, Ar, Het, Hal, \u2014(CY2)n\u2014SA, \u2014(CY2)n\u2014SCF3, \u2014(CY2)n\u2014SCN, \u2014(CY2)n\u2014CF3, \u2014(CY2)n\u2014OCF3, R, cycloalkyl, \u2014SCH3, \u2014SCN, \u2014CF3\u2014OCF3, \u2014OA, \u2014(CY2)n\u2014OH, \u2014(CY2)n\u2014CO2R, \u2014(CY2)n\u2014CN, \u2014(CY2)n-Hal, \u2014(CY2)n\u2014NR2, (CY2)n\u2014OA, (CY2)n\u2014OCOA, \u2014SCF3, (CY2)n\u2014CONR2, \u2014(CY2)n\u2014NHCOA, \u2014(CY2)n\u2014NHSO2A, SF5, Si(CH3)3, CO\u2014(CY2)n\u2014CH3, \u2014(CY2)n\u2014N-Pyrrolidone, (CH2)nNRCOOR, NRCOOR, NCO, (CH2)nCOOR, NCOOR, (CH2)nOH, NR(CH2)nNR2, C(OH)R2, NR(CH2)nOR, NCOR, (CH2)nAr, (CH2)nHet, (CH2)nR, (CH2)nX(CH2)nAr, (CH2)nX(CH2)nHet, (CH2)nCONR2, XCONR(CH2)nNR2, N(CH2)nXCOORCO(CH2)nAr, N(CH2)nXRCO(CH2)nAr, N(CH2)nXRCO(CH2)nXAr, N(CH2)nXRSO2(CH2)nAr, N(CH2)nNRCOORCO(CH2)nAr, N(CH2)nNR2CO(CH2)nAr, N(CH2)nNR2CO(CH2)nNRAr, N(CH2)nNR2SO2(CH2)nAr, N(CH2)nXRCO(CH2)nHet, N(CH2)nXRCO(CH2)nXHet, N(CH2)nXRSO2(CH2)nHet, N(CH2)nNRCOORCO(CH2)nHet, N(CH2)nNR2CO(CH2)nHet, N(CH2)nNR2CO(CH2)nNRHet,
Y denotes H, A, Hal, or OR,
A denotes Alkyl or Cycloalkyl, wherein one or more H-atoms can be replaced by Hal
Hal denotes F, Cl, Br or I,
R denotes H or A, in the case of geminal groups R together also \u2014(CH2)5\u2014, \u2014(CH2)4\u2014 or \u2014(CH2)n\u2014X\u2014(CH2)n, or \u2014(CH2)n\u2014Z\u2014(CH2)n,
X denotes O, S, NH or NA,
Q denotes CH2\u2014NH-A, CH2\u2014NH\u2014C(O)R1, CH2\u2014NH\u2014SO2R1,
Z denotes CH2, X, CHCONH2, CH(CH2)nNRCOOR, CHNRCOOR, NCHO, CHCON(R)2, CH(CH2)nCOOR, NCOOR, CH(CH2)nOH, N(CH2)nOH, CHNH2, CH(CH2)nNR2, CH(CH2)nNR2, C(OH)R, CHNCOR, NCOR, N(CH2)nAr, N(CH2)nHet, CHR, NR, CH(CH2)nAr, CH(CH(CH2)nHet, CH(CH2)nR, N(CH2)nCOOR, CH(CH2)nX(CH2)nAr, CH(CH2)nX(CH2)nHet, N(CH2)nCON(R)2, NSO2R, CHSO2N(R)2, XCONR(CH2)nN(R)2, NCO(CH2)nAr, NCO(CH2)nXAr, NSO2(CH2)nAr, NCO(CH2)nAr, NCO(CH2)nNRAr, NCO(CH2)nHet, NCO(CH2)nXHet, NSO2(CH2)nHet, NCO(CH2)nNRHet, N(CH2)nNR2CH, CHO(CH2)nN(R)2, CHX(CH2)nN(R)2, NCO(CH2)nNR2,
Ar denotes a monocyclic or bicyclic, saturated, unsaturated or aromatic carbocyclic ring having 6 to 14 carbon atoms which may be unsubstituted which is substituted in at least one position by Hal, NO2, CN, OR, A, \u2014(CY2)n\u2014OR, \u2014OCOR, \u2014(CY2)n\u2014CO2R, \u2014(CY2)n\u2014CN, \u2014NCOR, \u2014COR or \u2014(CY2)n\u2014NR2 or by Hal, NO2, CN, A, OR, OCOR, COR, NR2, CF3, OCF3, OCH(CF3)2,
Het denotes a monocyclic or bicyclic, saturated, unsaturated or aromatic heterocyclic ring having 1 to 4 N, O andor S atoms which may be unsubstituted or which is substituted in at least one position by Hal, NO2, CN, OR, A, \u2014(CY2)n\u2014OR, \u2014OCOR, \u2014(CY2)n\u2014CO2R, \u2014(CY2)n\u2014CN, \u2014NCOR, \u2014COR or \u2014(CY2)n\u2014NR2 or by Hal, NO2, CN, A, OR, OCOR, COR, NR2, CF3, OCF3, OCH(CF3)2, and
n denotes 0, 1, 2, 3, 4, 5, 6 or 7,
as well as their pharmaceutically acceptable tautomers and salts,
said process comprising:
A)
treating the racemic compound C, wherein Q is CH2NH2 or CH2NHA, with a chiral acid compound in a polar solvent to give enantiomerically enriched or pure dihydropyran methylamine salts;
and optionally using a base to obtain the free base from the dihydropyran methylamine salts;
or
B)
treating the racemic compound C, wherein Q is CH2NH2 or CH2NHA, with a chiral acid compound in a polar solvent to give the enantiomerically enriched or pure dihydropyran methylamine salts;
optionally using a base to obtain the free base from the dihydropyran methylamine salts, and
reacting the resulting compound with ClC(O)R1 or ClSO2R1 in the presence of a non nucleophilic base in a polar solvent;
or
C)
treating the racemic compound C, wherein Q is CH2NH2 or CH2NHA, with a chiral acid compound in a polar solvent to give the enantiomerically enriched or pure dihydropyran methylamine salts;
optionally using a base to obtain the free base from the dihydropyran methylamine salts, and
reacting the resulting compound with a primary amine NH2R1 with CDI in a solvent.
13. The process according to claim 12 for the manufacture of enantiomerically enriched or pure compounds of formula C:
wherein Q denotes CH2\u2014NH-A, CH2\u2014NH\u2014C(O)R1, CH2\u2014NH\u2014SO2R1, as well as their pharmaceutically acceptable tautomers and salts, said process comprising:
treating the racemic compound C, wherein Q is CH2NH2 or CH2NHA, with a chiral acid compound in a polar solvent to give the enantiomerically enriched or pure dihydropyran methylamine salts;
optionally using a base to obtain the free base from the dihydropyran methylamine salts, and
reacting the resulting compound with ClC(O)R1 or ClSO2R1 in the presence of a non nucleophilic base in a polar solvent.
14. The process according to claim 12 for the manufacture of enantiomerically enriched or pure compounds of formula C:
wherein Q denotes CH2\u2014NH-A, CH2\u2014NH\u2014C(O)R1, CH2\u2014NH\u2014SO2R1, as well as their pharmaceutically acceptable tautomers and salts, said process comprising:
treating the racemic compound C, wherein Q is CH2NH2 or CH2NHA, with a chiral acid compound in a polar solvent to give the enantiomerically enriched or pure dihydropyran methylamine salts;
optionally using a base to obtain the free base from the dihydropyran methylamine salts, and
reacting the resulting compound with a primary amine NH2R1 with CDI in a solvent.
15. The process according to claim 12, wherein
(a) Q is CH2NHMe, the chiral acid compound is L-tosylproline, the polar solvent ethanol and the base is NaOH; or
(b) Q is CH2NH2, and the chiral acid compound is (2R,3R)-(\u2212)-Di-O-benzoyl tartaric acid.
16. The process according to claim 13, wherein R1 is methyl, the chiral acid compound is L-tosylproline, the polar solvent ethanol, the base is NaOH and non nucleophilic base is triethylamine TEA.
17. The process according to claim 14, wherein R1 is CH2\u2014CH2\u2014N(CH3)2, the chiral acid compound is L-tosylproline, the polar solvent ethanol, the base is NaOH, the coupling agent is 1,1\u2032-carbonyldiimidazole and the solvent is CH2Cl2.
18. The process according to claim 1, wherein separation of the exo and endo compounds obtained, is achieved by recrystallization with chiral salts or acid.
19. The process according to claim 1, wherein compound C is obtained by
A)
treating the racemic compound C, wherein Q is CH2NH2 or CH2NHA, with a chiral acid compound in a polar solvent to give enantiomerically enriched or pure dihydropyran methylamine salts; and
optionally using a base to obtain the free base from the dihydropyran methylamine salts;
or
B)
treating the racemic compound C, wherein Q is CH2NH2 or CH2NHA, with a chiral acid compound in a polar solvent to give the enantiomerically enriched or pure dihydropyran methylamine salts;
optionally using a base to obtain the free base from the dihydropyran methylamine salts,
and reacting the resulting compound with ClC(O)R1 or ClSO2R1 in the presence of a non nucleophilic base in a polar solvent;
or
C)
treating the racemic compound C, wherein Q is CH2NH2 or CH2NHA, with a chiral acid compound in a polar solvent to give the enantiomerically enriched or pure dihydropyran methylamine salts;
optionally using a base to obtain the free base from the dihydropyran methylamine salts,
and reacting the resulting compound with a primary amine NH2R1 with 1,1\u2032-carbonyldiimidazole in a solvent.
20. The process according to claim 1, wherein said compound of formula I is a compound of formula Ia2 or formula Ib2
or a pharmaceutically acceptable tautomer or salt thereof.
21. The process according to claim 20, wherein enantiomerically enriched or pure compounds of formula Ia2 are obtained by recrystallization with (2R,3R)-(\u2212)-Di-O-benzoyl tartaric acid salt in EtOH.
22. The process according to claim 20, wherein enantiomerically enriched or pure compounds of formula Ib2 are obtained by recrystallization with HCl in EtOH.
23. The process according to claim 12 for the manufacture of enantiomerically enriched or pure compounds of formula C:
wherein
Q denotes CH2\u2014NH-A, CH2\u2014NH\u2014C(O)R1, CH2\u2014NH\u2014SO2R1, as well as their pharmaceutically acceptable tautomers and salts, said process comprising:
treating the racemic compound C, wherein Q is CH2NH2 or CH2NHA, with a chiral acid compound in a polar solvent to give enantiomerically enriched or pure dihydropyran methylamine salts;
and optionally using a base to obtain the free base from the dihydropyran methylamine salts.