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Cesium carbonate → Racemic methyl-4-(5-{3-[(5-fluoro-4-methylpyrimidin-2-yl)amino]-5-methylphenyl}-1,3-thiazol-2-yl)-4-hydroxy-2,2-dimethylcyclohexanecarboxylate

HRID 1040151
ノート
印刷プレビュー

反応式

HRID 1040151 の反応式
Cl[C:2]1[N:7]=[C:6]([CH3:8])[C:5]([F:9])=[CH:4][N:3]=1.[CH3:10][O:11][C:12]([CH:14]1[CH2:19][CH2:18][C:17]([C:21]2[S:22][C:23]([C:26]3[CH:31]=[C:30]([CH3:32])[CH:29]=[C:28]([NH2:33])[CH:27]=3)=[CH:24][N:25]=2)([OH:20])[CH2:16][C:15]1([CH3:35])[CH3:34])=[O:13].CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2.C([O-])([O-])=O.[Cs+].[Cs+]>CC([O-])=O.CC([O-])=O.[Pd+2]>[CH3:10][O:11][C:12]([CH:14]1[CH2:19][CH2:18][C:17]([C:21]2[S:22][C:23]([C:26]3[CH:31]=[C:30]([CH3:32])[CH:29]=[C:28]([NH:33][C:2]4[N:7]=[C:6]([CH3:8])[C:5]([F:9])=[CH:4][N:3]=4)[CH:27]=3)=[CH:24][N:25]=2)([OH:20])[CH2:16][C:15]1([CH3:35])[CH3:34])=[O:13]
参加物反応条件実験手順後処理出典と根拠反応ノート

参加物

6

反応物 4

HCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 207780732-Chloro-5-fluoro-4-methylpyrimidineHCID 67429727Methyl 4-(5-(3-amino-5-methylphenyl)thiazol-2-yl)-4-hydroxy-2,2-dimethylcyclohexanecarboxylate

生成物 1

HCID 67250082
Racemic methyl-4-(5-{3-[(5-fluoro-4-methylpyrimidin-2-yl)amino]-5-methylphenyl}-1,3-thiazol-2-yl)-4-hydroxy-2,2-dimethylcyclohexanecarboxylate
収率 86.5%

試薬・触媒・溶媒 1

HCID 167845palladium(II) acetate触媒

反応条件

温度
110 °C

実験手順

Racemic 2-chloro-5-fluoro-4-methylpyrimidine (50.0 mg, 0.341 mmol), methyl-4-[5-(3-amino-5-methylphenyl)-1,3-thiazol-2-yl]-4-hydroxy-2,2-dimethylcyclohexanecarboxylate (128 mg, 0.341 mmol), Pd(OAc)2 (15.3 mg, 0.0680 mmol), Xantphos (59.2 mg, 0.102 mmol), and Cs2CO3 (222 mg, 0.682 mmol) were combined in a flask and degassed with argon. To this solid mixture was added dioxane (2.0 mL), and the resulting mixture was degassed with argon for 5 min. The reaction mixture was heated to 110° C. for 1.5 h. The reaction was cooled to ambient temperature, then diluted with saturated aqueous NaCl and EtOAc. The layers were separated, and the aqueous layer was extracted with EtOAc. The combined organic layers were dried over sodium sulfate, filtered and concentrated in vacuo. The resulting crude product was purified by column chromatography on silica (10-30% EtOAc/hexanes gradient) to afford racemic methyl-4-(5-{3-[(5-fluoro-4-methylpyrimidin-2-yl)amino]-5-methylphenyl}-1,3-thiazol-2-yl)-4-hydroxy-2,2-dimethylcyclohexanecarboxylate (143 mg, 0.295 mmol, 86% yield). MS ESI: [M+H]+ m/z 485.

後処理

  1. customdegassed with argon
  2. additionTo this solid mixture was added dioxane (2.0 mL)
  3. customthe resulting mixture was degassed with argon for 5 min
  4. temperatureThe reaction was cooled to ambient temperature
  5. additiondiluted with saturated aqueous NaCl and EtOAc
  6. customThe layers were separated
  7. extractionthe aqueous layer was extracted with EtOAc
  8. dry with materialThe combined organic layers were dried over sodium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo
  11. customThe resulting crude product was purified by column chromatography on silica (10-30% EtOAc/hexanes gradient)

出典と根拠

ORDレコード
ord-20801557d81f42beb3e5c2f4a278a1c2
出典データセット
uspto-grants-2013_10
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US08551984B2

反応ノート

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