US10265307, Example 72-2 → N-{4-[(3S,5R)-3-Amino-5-(trifluoromethyl)piperidin-1-yl]-7-hydroxy-6,7-dihydro-5H-cyclopenta[b]pyridin-3-yl}-6-[2,6-difluoro-4-(1-hydroxy-1-methylethyl)phenyl]-5-fluoropyridine-2-carboxamide

HRID 1499624Notes

Reaction equation

HRID 1499624 reaction equation
[NH2:1][C@H:2]1[CH2:7][C@@H:6]([C:8]([F:11])([F:10])[F:9])[CH2:5][N:4]([C:12]2[C:17]([NH:18][C:19]([C:21]3[CH:26]=[CH:25][C:24]([F:27])=[C:23]([C:28]4[C:33]([F:34])=[CH:32][C:31]([C:35]([OH:38])([CH3:37])[CH3:36])=[CH:30][C:29]=4[F:39])[N:22]=3)=[O:20])=[CH:16][N:15]=[C:14]3[C@H:40]([OH:43])[CH2:41][CH2:42][C:13]=23)[CH2:3]1.N[C@H]1C[C@@H](C(F)(F)F)CN(C2C(NC(C3C=CC(F)=C(C4C(F)=CC(C(O)(C)C)=CC=4F)N=3)=O)=CN=C3[C@@H](O)CCC=23)C1>>[NH2:1][C@H:2]1[CH2:7][C@@H:6]([C:8]([F:9])([F:10])[F:11])[CH2:5][N:4]([C:12]2[C:17]([NH:18][C:19]([C:21]3[CH:26]=[CH:25][C:24]([F:27])=[C:23]([C:28]4[C:29]([F:39])=[CH:30][C:31]([C:35]([OH:38])([CH3:37])[CH3:36])=[CH:32][C:33]=4[F:34])[N:22]=3)=[O:20])=[CH:16][N:15]=[C:14]3[CH:40]([OH:43])[CH2:41][CH2:42][C:13]=23)[CH2:3]1

Participants

3

Reactant 2

HCID 86726841US10265307, Example 72-2HCID 86726842US10265307, Example 72-1

Product 1

HCID 86726840N-{4-[(3S,5R)-3-Amino-5-(trifluoromethyl)piperidin-1-yl]-7-hydroxy-6,7-dihydro-5H-cyclopenta[b]pyridin-3-yl}-6-[2,6-difluoro-4-(1-hydroxy-1-methylethyl)phenyl]-5-fluoropyridine-2-carboxamide

Procedure

The diastereoisomers correspond to the (7R) and (7S) diastereoisomers of the title compound, N-{4-[(3S,5R)-3-amino-5-(trifluoromethyl)piperidin-1-yl]-(7R)-7-hydroxy-6,7-dihydro-5H-cyclopenta[b]pyridin-3-yl}-6-[2,6-difluoro-4-(1-hydroxy-1-methylethyl)phenyl]-5-fluoropyridine-2-carboxamide and N-{4-[(3S,5R)-3-amino-5-(trifluoromethyl)piperidin-1-yl]-(7S)-7-hydroxy-6,7-dihydro-5H-cyclopenta[b]pyridin-3-yl}-6-[2,6-difluoro-4-(1-hydroxy-1-methylethyl)phenyl]-5-fluoropyridine-2-carboxamide. The alternative enantiomers, N-{4-[(3R,5S)-3-amino-5-(trifluoromethyl)piperidin-1-yl]-(7R)-7-hydroxy-6,7-dihydro-5H-cyclopenta[b]pyridin-3-yl}-6-[2,6-difluoro-4-(1-hydroxy-1-methylethyl)phenyl]-5-fluoropyridine-2-carboxamide and N-{4-[(3R,5S)-3-amino-5-(trifluoromethyl)piperidin-1-yl]-(7S)-7-hydroxy-6,7-dihydro-5H-cyclopenta[b]pyridin-3-yl}-6-[2,6-difluoro-4-(1-hydroxy-1-methylethyl)phenyl]-5-fluoropyridine-2-carboxamide, are prepared by an analogous route starting from using tert-butyl [(3R,5S)-1-(3-nitro-6,7-dihydro-5H-cyclopenta[b]pyridin-4-yl)-5-(trifluoromethyl)piperidin-3-yl]carbamate (Enantiomer 1) from step 1.

Sources & evidence

ORD record
ord-cfbe1042184c4f4f99e6b105e8ecfb50
Source dataset
uspto-grants-2015_12
Patent number
US09200004B2

Reaction notes

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