Potassium Carbonate → 2-Chloro-5-fluoro-4-(3-[(1S)-2-hydroxy-1-methylethoxy]-5-{[(1-methyl-1H-pyrazol-3-yl)amino]carbonyl}phenoxy)-N,N-dimethylbenzamide

HRID 20597ノート

反応式

HRID 20597 の反応式
[Si]([O:8][CH2:9][C@H:10]([CH3:28])[O:11][C:12]1[CH:13]=[C:14]([CH:24]=[C:25]([OH:27])[CH:26]=1)[C:15]([NH:17][C:18]1[CH:22]=[CH:21][N:20]([CH3:23])[N:19]=1)=[O:16])(C(C)(C)C)(C)C.C(=O)([O-])[O-].[K+].[K+].[Cl:35][C:36]1[CH:46]=[C:45](F)[C:44]([F:48])=[CH:43][C:37]=1[C:38]([N:40]([CH3:42])[CH3:41])=[O:39]>C(#N)C>[Cl:35][C:36]1[CH:46]=[C:45]([O:27][C:25]2[CH:24]=[C:14]([C:15]([NH:17][C:18]3[CH:22]=[CH:21][N:20]([CH3:23])[N:19]=3)=[O:16])[CH:13]=[C:12]([O:11][C@@H:10]([CH3:28])[CH2:9][OH:8])[CH:26]=2)[C:44]([F:48])=[CH:43][C:37]=1[C:38]([N:40]([CH3:42])[CH3:41])=[O:39]

参加物

5

反応物 3

HCID 11430Potassium CarbonateHCID 536296323-[((1S)-2-{[(1,1-dimethylethyl)(dimethyl)silyl]oxy}-1-methylethyl)oxy]-5-hydroxy-N-(1-methyl-1H-pyrazol-3-yl)benzamideHCID 593469042-chloro-4,5-difluoro-N,N-dimethylbenzamide

生成物 1

HCID 115840152-Chloro-5-fluoro-4-(3-[(1S)-2-hydroxy-1-methylethoxy]-5-{[(1-methyl-1H-pyrazol-3-yl)amino]carbonyl}phenoxy)-N,N-dimethylbenzamide収率 16.7%

試薬・触媒・溶媒 1

HCID 6342Acetonitrile溶媒

反応条件

温度
160 °C

実験手順

A suspension of 3-((1S)-2-{[tert-butyl(dimethyl)silyl]oxy}-1-methylethyloxy)-5-hydroxy-N-(1-methyl-1H-pyrazol-3-yl)benzamide (200 mg, 0.477 mmol), potassium carbonate (136 mg, 0.95 mmol) and 2-chloro-4,5-difluoro-N,N-dimethylbenzamide (106 mg, 0.45 mmol) in acetonitrile (3.5 mL) was heated in a microwave reactor at 160° C. for 2 hours. The reaction mixture was quenched with water and extracted with DCM (2×6 mL). The organic layer was dried (MgSO4), filtered and concentrated in vacuo. The residue was then chromatographed by preparatory reverse phase HPLC using a gradient of 5-95% acetonitrile in water (containing 0.2% TFA) on a Phenomenex Luna 10u C18 (2) 100A (150×21.2 mm) column to give the title compound (37 mg).

後処理

  1. customThe reaction mixture was quenched with water
  2. extractionextracted with DCM (2×6 mL)
  3. dry with materialThe organic layer was dried (MgSO4)
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe residue was then chromatographed by preparatory reverse phase HPLC

出典と根拠

ORDレコード
ord-7a1260f751614e20b093b816fb1e871f
出典データセット
uspto-grants-2010_06
特許番号
US07745475B2

反応ノート

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