1,1'-Carbonyldiimidazole → HCID 57512645, compound

HRID 14228Notes

Reaction equation

HRID 14228 reaction equation
[CH2:1]([N:4]([CH2:14][CH2:15][CH3:16])[C:5]1[CH:6]=[C:7]([CH:11]=[CH:12][N:13]=1)[C:8]([OH:10])=O)[CH2:2][CH3:3].C(N1C=CN=C1)(N1C=CN=C1)=O.[NH2:29][C@@H:30]([CH2:46][C:47]1[CH:52]=[C:51]([F:53])[CH:50]=[C:49]([F:54])[CH:48]=1)[C@H:31]([OH:45])[CH2:32][NH:33][C:34]1([C:37]2[CH:42]=[CH:41][CH:40]=[C:39]([C:43]#[CH:44])[CH:38]=2)[CH2:36][CH2:35]1>ClCCl>[F:53][C:51]1[CH:52]=[C:47]([CH:48]=[C:49]([F:54])[CH:50]=1)[CH2:46][C@H:30]([NH:29][C:8](=[O:10])[C:7]1[CH:11]=[CH:12][N:13]=[C:5]([N:4]([CH2:1][CH2:2][CH3:3])[CH2:14][CH2:15][CH3:16])[CH:6]=1)[C@H:31]([OH:45])[CH2:32][NH:33][C:34]1([C:37]2[CH:42]=[CH:41][CH:40]=[C:39]([C:43]#[CH:44])[CH:38]=2)[CH2:36][CH2:35]1

Participants

5

Reactant 3

HCID 682631,1'-CarbonyldiimidazoleHCID 21085461HCID 21085461, compoundHCID 57487321(2R,3S)-3-amino-4-(3,5-difluorophenyl)-1-{[1-(3-ethynylphenyl)cyclopropyl]amino]butan-2-ol

Product 1

HCID 57512645HCID 57512645, compoundYield 60%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

2-(Dipropylamino)isonicotinic acid (0.206 g) was dissolved in dichloromethane (10 mL). 1,1′-Carbonyldiimidazole was added (0.142 g) and the mixture was stirred for 2 h at room temperature, at which time (2R,3S)-3-amino-4-(3,5-difluorophenyl)-1-{[1-(3-ethynylphenyl)cyclopropyl]amino}butan-2-ol (0.284 g) in dichloromethane was added. The mixture was allowed to stir overnight and then was partitioned between dichloromethane, water, and brine, dried over sodium sulfate, filtered, and concentrated under reduced pressure. The concentrate was chromatographed on silica gel using methanol/dichloromethane (4/96) to give N-((1S,2R)-1-(3,5-difluorobenzyl)-3-{[1-(3-ethynylphenyl)cyclopropyl]amino}-2-hydroxypropyl)-2-(dipropylamino)isonicotinamide (0.268g). MS (ESI+) for C33H38F2N4O2+H1 m/z 561.30 (M+H)+.

Workup

  1. additionwas added
  2. customwas partitioned between dichloromethane, water, and brine
  3. dry with materialdried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customThe concentrate was chromatographed on silica gel

Sources & evidence

ORD record
ord-bb3aaf4bc2a64207940a041ea2cf1674
Source dataset
uspto-grants-2010_06
Patent number
US07727997B2

Reaction notes

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