1-(5-Cyano-2-pyridinyl)-4-piperidinecarboxylic acid → rac-[(3R,4S)-1-(5'-cyano-3,4,5,6-tetrahydro-2H-[1,2']bipyridinyl-4-carbonyl)-4-(4-fluoro-phenyl)-pyrrolidin-3-yl]-methyl-carbamic acid 4-fluoro-phenyl ester

HRID 587366Notes

Reaction equation

HRID 587366 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([O:8][C:9](=[O:24])[N:10]([C@@H:12]2[C@@H:16]([C:17]3[CH:22]=[CH:21][C:20]([F:23])=[CH:19][CH:18]=3)[CH2:15][NH:14][CH2:13]2)[CH3:11])=[CH:4][CH:3]=1.[C:25]([C:27]1[CH:28]=[CH:29][C:30]([N:33]2[CH2:38][CH2:37][CH:36]([C:39]([OH:41])=[O:40])[CH2:35][CH2:34]2)=[N:31][CH:32]=1)#[N:26]>>[F:1][C:2]1[CH:7]=[CH:6][C:5]([O:8][C:9](=[O:24])[N:10]([C@@H:12]2[C@@H:16]([C:17]3[CH:22]=[CH:21][C:20]([F:23])=[CH:19][CH:18]=3)[CH2:15][N:14]([C:39]([CH:36]3[CH2:35][CH2:34][N:33]([C:30]4[CH:29]=[CH:28][C:27]([C:25]#[N:26])=[CH:32][N:31]=4)[CH2:38][CH2:37]3)=[O:40])[CH2:13]2)[CH3:11])=[CH:4][CH:3]=1.[F:1][C:2]1[CH:7]=[CH:6][C:5]([O:8][C:9](=[O:24])[N:10]([C@H:12]2[C@H:16]([C:17]3[CH:22]=[CH:21][C:20]([F:23])=[CH:19][CH:18]=3)[CH2:15][N:14]([C:39]([CH:36]3[CH2:35][CH2:34][N:33]([C:30]4[CH:29]=[CH:28][C:27]([C:25]#[N:26])=[CH:32][N:31]=4)[CH2:38][CH2:37]3)=[O:41])[CH2:13]2)[CH3:11])=[CH:4][CH:3]=1

Participants

4

Reactant 2

HCID 162274741-(5-Cyano-2-pyridinyl)-4-piperidinecarboxylic acidHCID 67234033rac-[(3R,4S)-4-(4-fluoro-phenyl)-pyrrolidin-3-yl]-methyl-carbamic acid 4-fluoro-phenyl ester

Product 2

HCID 58303033rac-[(3R,4S)-1-(5'-cyano-3,4,5,6-tetrahydro-2H-[1,2']bipyridinyl-4-carbonyl)-4-(4-fluoro-phenyl)-pyrrolidin-3-yl]-methyl-carbamic acid 4-fluoro-phenyl esterHCID 58303146[(3S,4R)-1-(5'-cyano-3,4,5,6-tetrahydro-2H-[1,2']bipyridinyl-4-carbonyl)-4-(4-fluoro-phenyl)-pyrrolidin-3-yl]-methyl-carbamic acid 4-fluoro-phenyl ester

Procedure

In analogy to the procedure described for the synthesis of example 44 (step c), the title compound rac-[(3R,4S)-1-(5′-cyano-3,4,5,6-tetrahydro-2H-[1,2′]bipyridinyl-4-carbonyl)-4-(4-fluoro-phenyl)-pyrrolidin-3-yl]-methyl-carbamic acid 4-fluoro-phenyl ester was prepared from rac-[(3R,4S)-4-(4-fluoro-phenyl)-pyrrolidin-3-yl]-methyl-carbamic acid 4-fluoro-phenyl ester using 5′-cyano-3,4,5,6-tetrahydro-2H-[1,2′]bipyridinyl-4-carboxylic acid instead of 1-methylcyclopropane-1-carboxylic acid and was obtained as a brown semisolid. MS m/e: 562.1 [M]+. The racemate was then subjected to column chromatography on chiral phase to yield -[(3S,4R)-1-(5′-cyano-3,4,5,6-tetrahydro-2H-[1,2′]bipyridinyl-4-carbonyl)-4-(4-fluoro-phenyl)-pyrrolidin-3-yl]-methyl-carbamic acid 4-fluoro-phenyl ester (MS (m/e): 546.3 [M+H]+) as a yellow waxy solid and -[(3R,4S)-1-(5′-cyano-3,4,5,6-tetrahydro-2H-[1,2′]bipyridinyl-4-carbonyl)-4-(4-fluoro-phenyl)-pyrrolidin-3-yl]-methyl-carbamic acid 4-fluoro-phenyl ester (MS (m/e): 546.3 [M+H]+) as a yellow waxy solid.

Workup

  1. customIn analogy to the procedure described for the synthesis of example 44 (step c)
  2. customwas obtained as a brown semisolid

Sources & evidence

ORD record
ord-4ca06bc72db141e19d38dfefc525a38f
Source dataset
uspto-grants-2016_01
Patent number
US09226916B2

Reaction notes

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