Diisopropylethylamine → HCID 67378395, compound

HRID 1807300Notes

Reaction equation

HRID 1807300 reaction equation
[Cl:1][C:2]1[C:3]([F:31])=[C:4]([CH:8]2[C:12]([C:15]3[CH:20]=[CH:19][C:18]([Cl:21])=[CH:17][C:16]=3[F:22])([C:13]#[N:14])[CH:11]([CH2:23][C:24]([CH3:27])([CH3:26])[CH3:25])[NH:10][CH:9]2[C:28]([OH:30])=O)[CH:5]=[CH:6][CH:7]=1.C(N(CC)C(C)C)(C)C.[CH3:41][N:42]([CH2:44][C:45]1[CH:51]=[CH:50][C:48]([NH2:49])=[CH:47][CH:46]=1)[CH3:43]>ClCCl>[CH3:43][N:42]([CH2:44][C:45]1[CH:46]=[CH:47][C:48]([NH:49][C:28]([CH:9]2[CH:8]([C:4]3[CH:5]=[CH:6][CH:7]=[C:2]([Cl:1])[C:3]=3[F:31])[C:12]([C:15]3[CH:20]=[CH:19][C:18]([Cl:21])=[CH:17][C:16]=3[F:22])([C:13]#[N:14])[CH:11]([CH2:23][C:24]([CH3:25])([CH3:26])[CH3:27])[NH:10]2)=[O:30])=[CH:50][CH:51]=1)[CH3:41]

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 308051Benzenemethanamine, 4-amino-N,N-dimethyl-HCID 666882513-(3-Chloro-2-fluoro-phenyl)-4-(4-chloro-2-fluoro-phenyl)-4-cyano-5-(2,2-dimethyl-propyl)-pyrrolidine-2-carboxylic acid

Product 1

HCID 67378395HCID 67378395, compoundYield 70.5%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a stirred solution of rac-(2R,3S,4R,5S)-3-(3-chloro-2-fluorophenyl)-4-(4-chloro-2-fluorophenyl)-4-cyano-5-neopentylpyrrolidine-2-carboxylic acid (60 mg, 0.128 mmol) in dichloromethane (5.00 ml) were added N,N-DIISOPROPYLETHYLAMINE (100 mg) and 4-((dimethylamino)methyl)aniline (29.8 mg, 0.198 mmol) followed by N,N,N′,N′-tetramethyl-O-(7-aza-benzotriazol-1-yl)uranium hexafluorophosphate (HATU) (90.3 mg, 0.237 mmol, Chem-Impex) and the reaction mixture was stirred for 1 hr. The reaction mixture was diluted with CH2Cl2 (80 mL), washed with sat Na2CO3 (2×15 mL), water (2×15 mL) and evaporated. The crude material was purified by flash chromatography (silica gel, 4 g, 4% to 50% EtOAc in hexanes) to give rac-(2R,3S,4R,5S)-4-(4-Chloro-2-fluoro-phenyl)-3-(3-chloro-2-fluoro-phenyl)-4-cyano-5-(2,2-dimethyl-propyl)-pyrrolidine-2-carboxylic acid (4-dimethylaminomethyl-phenyl)-amide as white solid (54.1 mg, 70%). MS (ES+) m/z Calcd: [(M+H)+]: 599. found: 599.

Workup

  1. washwashed
  2. customevaporated
  3. customThe crude material was purified by flash chromatography (silica gel, 4 g, 4% to 50% EtOAc in hexanes)

Sources & evidence

ORD record
ord-7aae45b93a4b4abcb2c8421e3c04532a
Source dataset
uspto-grants-2013_01
Patent number
US08354444B2

Reaction notes

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