Diphenylphosphinic chloride → HCID 53357612, compound

HRID 1807285Notes

Reaction equation

HRID 1807285 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.[N:56]1[CH:61]=[C:60]([NH2:62])[CH:59]=[N:58][CH:57]=1>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]([CH3:25])([CH3:27])[CH3:26])[NH:10][C@H:9]2[C:28]([NH:62][C:60]2[CH:61]=[N:56][CH:57]=[N:58][CH:59]=2)=[O:29])[CH:5]=[CH:6][CH:7]=1

Participants

6

Reactant 4

HCID 73910Diphenylphosphinic chlorideHCID 81531DiisopropylethylamineHCID 344373Pyrimidin-5-amineHCID 59249226(2R,3S,4R,5S)-3-(3-chloro-2-fluorophenyl)-4-(4-chloro-2-fluorophenyl)-4-cyano-5-neopentylpyrrolidine-2-carboxylic acid

Product 1

HCID 53357612HCID 53357612, 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 (39.4 mg, 84.3 mmol) in dichloromethane (3 ml) was reacted with DIPEA (44.5 mg, 0.343 mmol) and DIPHENYLPHOSPHINIC CHLORIDE (49.7 mg, 0.210 mmol) and stirred for 20 min under argon. PYRIMIDIN-5-AMINE (8.3 mg, 0.0829 mmol, Ark Pharm) was added and stirred 2.5 hrs. The reaction mixture was diluted with dichloromethane, washed with water then with sat. NaHCO3, water, and sat. NaCl. After drying over Na2SO4 the crude material was purified by silica gel chromatography with ethyl acetate and n-hexanes giving chiral (2R,3S,4R,5S)-3-(3-chloro-2-fluorophenyl)-4-(4-chloro-2-fluorophenyl)-4-cyano-5-neopentyl-N-(pyrimidin-5-yl)pyrrolidine-2-carboxamide (35.7 mg., 77%) as a white lyophilized solid. MS (ES+) m/z Calcd: [(M+H)+]: 544.14. found: 544.0.

Workup

  1. stirringstirred 2.5 hrs
  2. washwashed 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 chiral (2R,3S,4R,5S)-3-(3-chloro-2-fluorophenyl)-4-(4-chloro-2-fluorophenyl)-4-cyano-5-neopentyl-N-(pyrimidin-5-yl)pyrrolidine-2-carboxamide (35.7 mg., 77%) as

Sources & evidence

ORD record
ord-7230da2df5544d9cbe3d1156dd973a1b
Source dataset
uspto-grants-2013_01
Patent number
US08354444B2

Reaction notes

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