Methanesulfonyl chloride → LGX-818

HRID 1889256Notes

Reaction equation

HRID 1889256 reaction equation
[CH3:1][S:2](Cl)(=[O:4])=[O:3].[NH2:6][C:7]1[C:8]([F:37])=[C:9]([C:14]2[C:18]([C:19]3[CH:24]=[CH:23][N:22]=[C:21]([NH:25][CH2:26][C@@H:27]([NH:29][C:30](=[O:33])[O:31][CH3:32])[CH3:28])[N:20]=3)=[CH:17][N:16]([CH:34]([CH3:36])[CH3:35])[N:15]=2)[CH:10]=[C:11]([Cl:13])[CH:12]=1.C(=O)(O)[O-].[Na+]>C(Cl)Cl.N1C=CC=CC=1>[Cl:13][C:11]1[CH:12]=[C:7]([NH:6][S:2]([CH3:1])(=[O:4])=[O:3])[C:8]([F:37])=[C:9]([C:14]2[C:18]([C:19]3[CH:24]=[CH:23][N:22]=[C:21]([NH:25][CH2:26][C@@H:27]([NH:29][C:30](=[O:33])[O:31][CH3:32])[CH3:28])[N:20]=3)=[CH:17][N:16]([CH:34]([CH3:35])[CH3:36])[N:15]=2)[CH:10]=1

Participants

6

Reactant 3

HCID 31297Methanesulfonyl chlorideHCID 516892Sodium BicarbonateHCID 70313839CarbaMic acid, N-[(1S)-2-[[4-[3-(3-aMino-5-chloro-2-fluorophenyl)-1-(1-Methylethyl)-1H-pyrazol-4-yl]-2-pyriMidinyl]aMino]-1-Methylethyl]-, Methyl ester

Product 1

HCID 50922675LGX-818

Reagents, catalysts & solvents 2

HCID 1049PyridineSolventHCID 6344DichloromethaneSolvent

Procedure

Methanesulfonyl chloride (0.277 mL, 3.57 mmol) was added to a solution of (S)-methyl 1-(4-(3-(3-amino-5-chloro-2-fluorophenyl)-1-isopropyl-1H-pyrazol-4-yl)pyrimidin-2-ylamino)propan-2-ylcarbamate (550 mg, 1.2 mmol) in DCM (30 mL) and pyridine (10 mL), and the mixture was stirred at rt for 16 h. Aqueous sodium bicarbonate solution was added, and the mixture was extracted with ethyl acetate and washed with brine. The organic phase was dried over sodium sulfate and concentrated. The crude product was purified by silica gel chromatography (60:1 to 40:1 DCM/methanol) to provide the title compound. An alternative synthesis is described in example 6, infra.

Workup

  1. extractionthe mixture was extracted with ethyl acetate
  2. washwashed with brine
  3. dry with materialThe organic phase was dried over sodium sulfate
  4. concentrationconcentrated
  5. customThe crude product was purified by silica gel chromatography (60:1 to 40:1 DCM/methanol)

Sources & evidence

ORD record
ord-b7fb276cebea498b9f8ce6222fc51fc8
Source dataset
uspto-grants-2013_08
Patent number
US08501758B2

Reaction notes

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