Diethylene Glycol → HCID 72550677, compound

HRID 2206379Notes

Reaction equation

HRID 2206379 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.C(N(CC)CC)C.O=C1N(P(Cl)(N2CCOC2=O)=O)CCO1.[O:65]([CH2:69][CH2:70]O)[CH2:66][CH2:67][OH:68]>C(Cl)Cl>[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][CH2:70][CH2:69][O:65][CH2:66][CH2:67][OH:68])=[O:36])=[CH:33][C:32]=2[O:40][CH3:41])=[O:29])[CH:5]=[CH:6][CH:7]=1

Participants

6

Reactant 4

HCID 8117Diethylene GlycolHCID 8471TriethylamineHCID 152842Bis(2-oxo-3-oxazolidinyl)phosphinic chlorideHCID 53358942Idasanutlin

Product 1

HCID 72550677HCID 72550677, compoundYield 23.8%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a suspension of 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 (150 mg, 0.243 mmol) in methylene chloride (8 mL) was added triethylamine (72.0 mg, 0.10 mL, 0.717 mmol) followed by bis(2-oxo-3-oxazolidinyl)phosphinic chloride (Aldrich, 92 mg, 0.365 mmol). The mixture was stirred at room temperature for 10 min before 2,2′-oxydiethanol (Aldrich, 154 mg, 0.14 mL, 1.45 mmol) was added. This reaction mixture was stirred at room temperature overnight. It was then diluted with methylene chloride and washed with water, brine and concentrated to dryness. The crude material was purified by flash chromatography (eluting with hexane/ethyl acetate, 80/20 to 10/90) to give chiral 2-(2-hydroxyethoxy)ethyl 4-((2R,3S,4R,5S)-3-(3-chloro-2-fluorophenyl)-4-(4-chloro-2-fluorophenyl)-4-cyano-5-neopentylpyrrolidine-2-carboxamido)-3-methoxybenzoate as a white solid (40.8 mg, 23% yield). MS (ES+) m/z calcd. for C35H38Cl2F2N3O6 [(M+H)+]: 704. found: 704.

Workup

  1. additionwas added
  2. washwashed with water, brine
  3. concentrationconcentrated to dryness
  4. customThe crude material was purified by flash chromatography (eluting with hexane/ethyl acetate, 80/20 to 10/90)

Sources & evidence

ORD record
ord-e82950b9a381431e9218095c9d7bb75e
Source dataset
uspto-grants-2016_06
Patent number
US09371280B2

Reaction notes

Loading…