5-Acetyl-2-bromopyridine → [(3S,4R)-1-(5'-Acetyl-3,4,5,6-tetrahydro-2H-[1,2']bipyridinyl-4-carbonyl)-4-(3,4-dichloro-phenyl)-pyrrolidin-3-yl]-ethyl-carbamic acid 4-fluoro-phenyl ester

HRID 527504Notes

Reaction equation

HRID 527504 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([O:8][C:9](=[O:34])[N:10]([C@H:13]2[C@H:17]([C:18]3[CH:23]=[CH:22][C:21]([Cl:24])=[C:20]([Cl:25])[CH:19]=3)[CH2:16][N:15]([C:26]([CH:28]3[CH2:33][CH2:32][NH:31][CH2:30][CH2:29]3)=[O:27])[CH2:14]2)[CH2:11][CH3:12])=[CH:4][CH:3]=1.[C:35]([C:38]1[CH:39]=[CH:40][C:41](Br)=[N:42][CH:43]=1)(=[O:37])[CH3:36]>>[F:1][C:2]1[CH:7]=[CH:6][C:5]([O:8][C:9](=[O:34])[N:10]([C@H:13]2[C@H:17]([C:18]3[CH:23]=[CH:22][C:21]([Cl:24])=[C:20]([Cl:25])[CH:19]=3)[CH2:16][N:15]([C:26]([CH:28]3[CH2:33][CH2:32][N:31]([C:41]4[CH:40]=[CH:39][C:38]([C:35](=[O:37])[CH3:36])=[CH:43][N:42]=4)[CH2:30][CH2:29]3)=[O:27])[CH2:14]2)[CH2:11][CH3:12])=[CH:4][CH:3]=1

Participants

3

Reactant 2

HCID 156681955-Acetyl-2-bromopyridineHCID 67237755[(3S,4R)-4-(3,4-Dichloro-phenyl)-1-(piperidine-4-carbonyl)-pyrrolidin-3-yl]-ethyl-carbamic acid 4-fluoro-phenyl ester

Product 1

HCID 53245788[(3S,4R)-1-(5'-Acetyl-3,4,5,6-tetrahydro-2H-[1,2']bipyridinyl-4-carbonyl)-4-(3,4-dichloro-phenyl)-pyrrolidin-3-yl]-ethyl-carbamic acid 4-fluoro-phenyl ester

Procedure

After removal of the Boc-protecting group under acidic conditions, in analogy to the procedure described for the synthesis of {(3R,4S)-4-(4-Chloro-phenyl)-1-[1-(5-cyano-pyrimidin-2-yl)-piperidine-4-carbonyl]-pyrrolidin-3-yl}-ethyl-carbamic acid 4-fluoro-phenyl ester (example 7, g) the title compound was prepared from [(3S,4R)-4-(3,4-Dichloro-phenyl)-1-(piperidine-4-carbonyl)-pyrrolidin-3-yl]-ethyl-carbamic acid 4-fluoro-phenyl ester and 5-acetyl-2-bromopyridine as off-white foam. MS m/e: 627.3 [M+H]+.

Workup

  1. customAfter removal of the Boc-
  2. customin analogy to the procedure described for the synthesis of {(3R,4S)-4-(4-Chloro-phenyl)-1-[1-(5-cyano-pyrimidin-2-yl)-piperidine-4-carbonyl]-pyrrolidin-3-yl}-ethyl-carbamic acid 4-fluoro-phenyl ester (example 7, g) the title compound

Sources & evidence

ORD record
ord-a181afa1543a4a65a7569c4a5a9d02c5
Source dataset
uspto-grants-2016_05
Patent number
US09346786B2

Reaction notes

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