Diphenylphosphinic chloride → HCID 178499041, compound

HRID 1807286Notes

Reaction equation

HRID 1807286 reaction equation
[Cl:1][C:2]1[C:3]([F:31])=[C:4]([C@@H: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])[C@H:11]([CH2:23][C:24]([CH3:27])([CH3:26])[CH3:25])[NH:10][C@H:9]2[C:28](O)=[O:29])[CH:5]=[CH:6][CH:7]=1.CCN(C(C)C)C(C)C.C1(P(Cl)(C2C=CC=CC=2)=O)C=CC=CC=1.[CH3:56][O:57][C:58]([C:60]1[NH:64][C:63]2[CH:65]=[CH:66][C:67]([NH2:69])=[CH:68][C:62]=2[N:61]=1)=[O:59]>ClCCl>[Cl:1][C:2]1[C:3]([F:31])=[C:4]([C@@H: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])[C@H:11]([CH2:23][C:24]([CH3:26])([CH3:27])[CH3:25])[NH:10][C@H:9]2[C:28]([NH:69][C:67]2[CH:66]=[CH:65][C:63]3[NH:64][C:60]([C:58]([O:57][CH3:56])=[O:59])=[N:61][C:62]=3[CH:68]=2)=[O:29])[CH:5]=[CH:6][CH:7]=1

Participants

6

Reactant 4

HCID 73910Diphenylphosphinic chlorideHCID 81531DiisopropylethylamineHCID 59249226(2R,3S,4R,5S)-3-(3-chloro-2-fluorophenyl)-4-(4-chloro-2-fluorophenyl)-4-cyano-5-neopentylpyrrolidine-2-carboxylic acidHCID 178499038HCID 178499038, compound

Product 1

HCID 178499041HCID 178499041, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

A solution of chiral (2R,3S,4R,5S)-3-(3-chloro-2-fluoro-phenyl)-4-(4-chloro-2-fluoro-phenyl)-4-cyano-5-(2,2-dimethyl-propyl)-pyrrolidine-2-carboxylic acid (60.3 mg, 0.129 mmol) in dichloromethane (3 ml) was reacted with DIPEA (66.8 mg, 0.514 mmol) and DIPHENYLPHOSPHINIC CHLORIDE (75.7 mg, 0.320 mmol) and stirred for 20 min under argon. 5-AMINO-1H-BENZOIMIDAZOLE-2-CARBOXYLIC ACID METHYL ESTER (25.7 mg, 0.134 mmol, Biofine) was added and stirred 2.5 hrs. The reaction mixture was diluted with dichloromethane and extracted with water then with sat'd NaHCO3, water, and brine. After drying over Na2SO4 the crude material was purified by silica gel chromatography with ethyl acetate and n-hexanes giving a white lyophilized solid, chiral methyl 542R,3S,4R,5S)-3-(3-chloro-2-fluorophenyl)-4-(4-chloro-2-fluorophenyl)-4-cyano-5-neopentylpyrrolidine-2-carboxamido)-1H-benzo[d]imidazole-2-carboxylate (43 mg, 52%). MS (ES+) m/z Calcd: [(M+H)+]: 640.16. found: 640.1.

Workup

  1. stirringstirred 2.5 hrs
  2. extractionextracted with water
  3. dry with materialAfter drying over Na2SO4 the crude material
  4. customwas purified by silica gel chromatography with ethyl acetate and n-hexanes giving

Sources & evidence

ORD record
ord-cc59b394f4fc485b84dc2c9d78f06e4f
Source dataset
uspto-grants-2013_01
Patent number
US08354444B2

Reaction notes

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