Diisopropylethylamine → HCID 53358114, compound

HRID 1807301Notes

Reaction equation

HRID 1807301 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](O)=[O:29])[CH:5]=[CH:6][CH:7]=1.C(N(CC)C(C)C)(C)C.[NH2:41][C:42]1[CH:43]=[CH:44][C:45]([N:51]2[CH2:55][CH2:54][CH2:53][CH2:52]2)=[C:46]([CH:50]=1)[C:47]([OH:49])=[O:48]>ClCCl>[Cl:21][C:18]1[CH:19]=[CH:20][C:15]([C@@:12]2([C:13]#[N:14])[C@H:11]([CH2:23][C:24]([CH3:27])([CH3:25])[CH3:26])[NH:10][C@@H:9]([C:28]([NH:41][C:42]3[CH:43]=[CH:44][C:45]([N:51]4[CH2:55][CH2:54][CH2:53][CH2:52]4)=[C:46]([CH:50]=3)[C:47]([OH:49])=[O:48])=[O:29])[C@@H:8]2[C:4]2[CH:5]=[CH:6][CH:7]=[C:2]([Cl:1])[C:3]=2[F:31])=[C:16]([F:22])[CH:17]=1

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 609825HCID 609825, compoundHCID 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 53358114HCID 53358114, compoundYield 17.4%

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 (99.6 mg, 0.770 mmol) and N,N,N′,N′-tetramethyl-O-(7-aza-benzotriazol-1-yl)uranium hexafluorophosphate (HATU) (90.3 mg, 0.237 mmol, Chem-Impex) followed by 5-amino-2-(pyrrolidin-1-yl)benzoic acid (38.5 mg, 0.187 mmol, Array). The reaction mixture was stirred for 2 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, 8 g, 0.5% to 5% MeOH in CH2Cl2) to give rac-5-{[(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-carbonyl]-amino}-2-pyrrolidin-1-yl-benzoic acid as white solid (14.6 mg, 15.4%). MS (ES+) m/z Calcd: [(M+H)+]: 655. found: 655.

Workup

  1. washwashed
  2. customevaporated
  3. customThe crude material was purified by flash chromatography (silica gel, 8 g, 0.5% to 5% MeOH in CH2Cl2)

Sources & evidence

ORD record
ord-362f984e8c6b426489bc2c0cf905a538
Source dataset
uspto-grants-2013_01
Patent number
US08354444B2

Reaction notes

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