Acetyl chloride → Acetic acid 4-{(3R,4S)-3-(4-chloro-phenyl)-4-[ethyl-(4-fluoro-phenoxycarbonyl)-amino]-pyrrolidine-1-carbonyl}-3,4,5,6-tetrahydro-2H-[1,2']bipyridinyl-5'-yl ester

HRID 527506Notes

Reaction equation

HRID 527506 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([O:8][C:9](=[O:41])[N:10]([C@H:13]2[C@H:17]([C:18]3[CH:23]=[CH:22][C:21](F)=[CH:20][CH:19]=3)[CH2:16][N:15]([C:25]([CH:27]3[CH2:32][CH2:31][N:30]([C:33]4[CH:38]=[CH:37][C:36](C#N)=[CH:35][N:34]=4)[CH2:29][CH2:28]3)=[O:26])[CH2:14]2)[CH2:11][CH3:12])=[CH:4][CH:3]=1.FC1C=CC(OC(=O)N([C@H]2[C@H](C3C=CC([Cl:65])=CC=3)CNC2)CC)=CC=1.OC1C=CC(N2CC[CH:77]([C:80]([OH:82])=[O:81])CC2)=NC=1.C(Cl)(=O)C>>[Cl:65][C:21]1[CH:22]=[CH:23][C:18]([C@H:17]2[C@H:13]([N:10]([CH2:11][CH3:12])[C:9]([O:8][C:5]3[CH:4]=[CH:3][C:2]([F:1])=[CH:7][CH:6]=3)=[O:41])[CH2:14][N:15]([C:25]([CH:27]3[CH2:32][CH2:31][N:30]([C:33]4[CH:38]=[CH:37][C:36]([O:82][C:80](=[O:81])[CH3:77])=[CH:35][N:34]=4)[CH2:29][CH2:28]3)=[O:26])[CH2:16]2)=[CH:19][CH:20]=1

Participants

5

Reactant 4

HCID 6367Acetyl chlorideHCID 53246272[(3S,4R)-1-(5'-Cyano-3,4,5,6-tetrahydro-2H-[1,2']bipyridinyl-4-carbonyl)-4-(4-fluoro-phenyl)-pyrrolidin-3-yl]-ethyl-carbamic acid 4-fluoro-phenyl esterHCID 58312626[(3S,4R)-4-(4-Chloro-phenyl)-pyrrolidin-3-yl]-ethyl-carbamic acid 4-fluoro-phenyl esterHCID 672348131-(5-Hydroxypyridin-2-yl)piperidine-4-carboxylic acid

Product 1

HCID 58312651Acetic acid 4-{(3R,4S)-3-(4-chloro-phenyl)-4-[ethyl-(4-fluoro-phenoxycarbonyl)-amino]-pyrrolidine-1-carbonyl}-3,4,5,6-tetrahydro-2H-[1,2']bipyridinyl-5'-yl ester

Procedure

In analogy to the procedure described for the synthesis of [(3S,4R)-1-(5′-Cyano-3,4,5,6-tetrahydro-2H-[1,2′]bipyridinyl-4-carbonyl)-4-(4-fluoro-phenyl)-pyrrolidin-3-yl]-ethyl-carbamic acid 4-fluoro-phenyl ester (example 35, step f) the intermediate was prepared from [(3S,4R)-4-(4-Chloro-phenyl)-pyrrolidin-3-yl]-ethyl-carbamic acid 4-fluoro-phenyl ester and 1-(5-hydroxypyridin-2-yl)piperidine-4-carboxylic acid. Afterwards, acetyl chloride was added and stirring was continued for 30 min at room temperature. The mixture was directly subjected to preparative HPLC on reversed phase eluting with a gradient formed from acetonitrile, water and NEt3. The product containing fractions were evaporated to yield the title compound as off-white solid. MS m/e: 608.2 [M+H]+.

Workup

  1. washeluting with a gradient
  2. customformed from acetonitrile, water and NEt3
  3. additionThe product containing fractions
  4. customwere evaporated

Sources & evidence

ORD record
ord-6c6cdc2bbb7945fc86058fc9b4f7bf70
Source dataset
uspto-grants-2016_05
Patent number
US09346786B2

Reaction notes

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