Triethylamine → HCID 72550899, compound

Reaction equation

[Cl:1][C:2]1[C:3]([F:42])=[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]([NH:30][C:31]2[CH:39]=[CH:38][C:34]([C:35]([OH:37])=[O:36])=[CH:33][C:32]=2[O:40][CH3:41])=[O:29])[CH:5]=[CH:6][CH:7]=1.[I:43][CH:44](O)[CH3:45].O=C1N(P(Cl)(N2CCOC2=O)=O)CCO1.C(N(CC)CC)C>>[Cl:1][C:2]1[C:3]([F:42])=[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:30][C:31]2[CH:39]=[CH:38][C:34]([C:35]([O:37][CH2:45][CH2:44][I:43])=[O:36])=[CH:33][C:32]=2[O:40][CH3:41])=[O:29])[CH:5]=[CH:6][CH:7]=1

Participants

Reactant 4

HCID 8471Triethylamine

HCID 152842Bis(2-oxo-3-oxazolidinyl)phosphinic chloride

HCID 178599451-Iodoethanol

HCID 53358942Idasanutlin

Product 1

HCID 72550899HCID 72550899, compoundYield 55%

Procedure

In a manner similar to the method described in Example 1, chiral 4-((2R,3S,4R,5S)-3-(3-chloro-2-fluorophenyl)-4-(4-chloro-2-fluorophenyl)-4-cyano-5-neopentylpyrrolidine-2-carboxamido)-3-methoxybenzoic acid (200 mg, 0.324 mmol) was reacted with iodoethanol (Aldrich, 220 mg, 1.28 mmol) in the presence of bis(2-oxo-3-oxazolidinyl)phosphinic chloride (Aldrich, 121.6 mg, 0.478 mmol), triethylamine (203 mg, 2.00 mmol) to give chiral 2-iodoethyl 4-((2R,3S,4R,5S)-3-(3-chloro-2-fluorophenyl)-4-(4-chloro-2-fluorophenyl)-4-cyano-5-neopentylpyrrolidine-2-carboxamido)-3-methoxybenzoate as an off-white solid (137.4 mg, 55% yield). MS (ES+) m/z calcd. for C33H33Cl2F2IN3O4: [(M+H)+]: 770. found: 770.