Dimethylformamide → HCID 72548158, compound

HRID 2206429Notes

Reaction equation

HRID 2206429 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.Cl[CH2:44][C:45]([NH:47][CH2:48][CH:49]1[CH2:53][O:52][C:51]([CH3:55])([CH3:54])[O:50]1)=[O:46].CN(C)C=O>O>[CH3:54][C:51]1([CH3:55])[O:50][CH:49]([CH2:48][NH:47][C:45]([CH2:44][O:36][C:35](=[O:37])[C:34]2[CH:38]=[CH:39][C:31]([NH:30][C:28]([C@H:9]3[C@H:8]([C:4]4[CH:5]=[CH:6][CH:7]=[C:2]([Cl:1])[C:3]=4[F:42])[C@:12]([C:15]4[CH:20]=[CH:19][C:18]([Cl:21])=[CH:17][C:16]=4[F:22])([C:13]#[N:14])[C@H:11]([CH2:23][C:24]([CH3:26])([CH3:27])[CH3:25])[NH:10]3)=[O:29])=[C:32]([O:40][CH3:41])[CH:33]=2)=[O:46])[CH2:53][O:52]1

Participants

5

Reactant 3

HCID 6228DimethylformamideHCID 53358942IdasanutlinHCID 86704083HCID 86704083, compound

Product 1

HCID 72548158HCID 72548158, compoundYield 24%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
50 °C

Procedure

In a 15 mL pressure tube, 4-((2R,3S,4R,5S)-3-(3-chloro-2-fluorophenyl)-4-(4-chloro-2-fluorophenyl)-4-cyano-5-neopentylpyrrolidine-2-carboxamido)-3-methoxybenzoic acid (prepared as described in US20100152190A1, 300 mg, 487 μmol) and 2-chloro-N-((2,2-dimethyl-1,3-dioxolan-4-yl)methyl)acetamide (101 mg, 487 μmol) were combined with dry dimethyl formamide (5 mL) to give a white suspension. The tube was capped and heated at 50° C. overnight. The reaction mixture was cooled down to room temperature. It was poured into water and extracted with ethyl acetate (2×). The ethyl acetate layers were combined, dried over anhydrous sodium sulfate, filtered and concentrated. The residue was purified with flash chromatography (24 g pre-packed silica gel column, eluted with methanol in ethyl acetate) to give 4-{[(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}-3-methoxy-benzoic acid [(2,2-dimethyl-[1,3]dioxolan-4-ylmethyl)-carbamoyl]-methyl ester as an off-white solid (92 mg, 24% yield). LCMS (ES+) m/z calcd. for C39H42Cl2F2N4O7 [(M+H)+]: 787. found: 787.

Workup

  1. customto give a white suspension
  2. customThe tube was capped
  3. temperatureThe reaction mixture was cooled down to room temperature
  4. extractionextracted with ethyl acetate (2×)
  5. dry with materialdried over anhydrous sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe residue was purified with flash chromatography (24 g pre-packed silica gel column, eluted with methanol in ethyl acetate)

Sources & evidence

ORD record
ord-688254d236b9400abd35a9f67f3ef35e
Source dataset
uspto-grants-2016_06
Patent number
US09371280B2

Reaction notes

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