Lithium Hexamethyldisilazide → N-{5-[(2-Chloro-4-pyrimidinyl)acetyl]-2-fluorophenyl}-2,6-difluorobenzenesulfonamide

HRID 590046Notes

Reaction equation

HRID 590046 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([F:8])[C:3]=1[S:9]([NH:12][C:13]1[CH:14]=[C:15]([CH:21]=[CH:22][C:23]=1[F:24])[C:16](OCC)=[O:17])(=[O:11])=[O:10].[Li+].C[Si]([N-][Si](C)(C)C)(C)C.[Cl:35][C:36]1[N:41]=[C:40]([CH3:42])[CH:39]=[CH:38][N:37]=1>C1COCC1>[Cl:35][C:36]1[N:41]=[C:40]([CH2:42][C:16]([C:15]2[CH:21]=[CH:22][C:23]([F:24])=[C:13]([NH:12][S:9]([C:3]3[C:2]([F:1])=[CH:7][CH:6]=[CH:5][C:4]=3[F:8])(=[O:11])=[O:10])[CH:14]=2)=[O:17])[CH:39]=[CH:38][N:37]=1

Participants

5

Reactant 3

HCID 2733832Lithium HexamethyldisilazideHCID 116296072-Chloro-4-methylpyrimidineHCID 57989990Ethyl 3-{[(2,6-difluorophenyl)sulfonyl]amino}-4-fluorobenzoate

Product 1

HCID 57989679N-{5-[(2-Chloro-4-pyrimidinyl)acetyl]-2-fluorophenyl}-2,6-difluorobenzenesulfonamideYield 50%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Procedure

To a solution of ethyl 3-{[(2,6-difluorophenyl)sulfonyl]amino}-4-fluorobenzoate (5.0 g, 13.9 mmol) in THF (100 mL) was added 1.0M LiHMDS in THF (34.8 mL, 34.8 mmol). A solution of 2-chloro-4-methylpyrimidine (2.7 g, 20.9 mmol) in THF (100 mL) was added dropwise over 30 min, and the reaction was stirred overnight at rt. The reaction was quenched with 10 mL of MeOH and concentrated, and the residue was partitioned between EtOAc and saturated aqueous NaHCO3. The aqueous layer was extracted with 2×50 mL EtOAc, and the combined organic layers were passed through a pad of silica gel, concentrated, and adsorbed onto silica gel. The crude product was purified via flash chromatography with 0-100% EtOAc/DCM to generate 3.07 g (50% yield) of the title compound as a white powder. MS (ESI): 443 (M+H).

Workup

  1. customThe reaction was quenched with 10 mL of MeOH
  2. concentrationconcentrated
  3. customthe residue was partitioned between EtOAc and saturated aqueous NaHCO3
  4. extractionThe aqueous layer was extracted with 2×50 mL EtOAc
  5. concentrationconcentrated
  6. customThe crude product was purified via flash chromatography with 0-100% EtOAc/DCM

Sources & evidence

ORD record
ord-9c45c2b9f13b459a8ea20abf2c20974f
Source dataset
uspto-grants-2016_01
Patent number
US09233956B2

Reaction notes

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