Potassium Carbonate → 1-(5-{3-[(5-Chloro-4-methylpyrimidin-2-yl)amino]-5-methylphenyl}-1,3-thiazol-2-yl)cyclobutanol

HRID 1040132ノート

反応式

HRID 1040132 の反応式
Cl[C:2]1[N:7]=[C:6]([CH3:8])[C:5]([Cl:9])=[CH:4][N:3]=1.[NH2:10][C:11]1[CH:12]=[C:13]([C:18]2[S:22][C:21]([C:23]3([OH:27])[CH2:26][CH2:25][CH2:24]3)=[N:20][CH:19]=2)[CH:14]=[C:15]([CH3:17])[CH:16]=1.CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C.C(=O)([O-])[O-].[K+].[K+]>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[Cl:9][C:5]1[C:6]([CH3:8])=[N:7][C:2]([NH:10][C:11]2[CH:12]=[C:13]([C:18]3[S:22][C:21]([C:23]4([OH:27])[CH2:26][CH2:25][CH2:24]4)=[N:20][CH:19]=3)[CH:14]=[C:15]([CH3:17])[CH:16]=2)=[N:3][CH:4]=1

参加物

6

反応物 4

HCID 11430Potassium CarbonateHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 212786212,5-Dichloro-4-methylpyrimidineHCID 584563951-[5-(3-Amino-5-methylphenyl)-1,3-thiazol-2-yl]cyclobutanol

生成物 1

HCID 584562941-(5-{3-[(5-Chloro-4-methylpyrimidin-2-yl)amino]-5-methylphenyl}-1,3-thiazol-2-yl)cyclobutanol収率 44.7%

試薬・触媒・溶媒 1

HCID 9811564Bis(dibenzylideneacetone)palladium触媒

反応条件

温度
90 °C

実験手順

A flask was charged with a stir bar, 2,5-dichloro-4-methylpyrimidine (63 mg, 0.38 mmol), Intermediate 15 (100 mg, 0.38 mmol), Pd2(dba)3 (35 mg, 0.038 mmol), XPhos (92 mg, 0.19 mmol), and potassium carbonate (106 mg, 0.768 mmol). The vial was evacuated and backfilled with argon three times. Fully degassed tent-amyl alcohol (1.3 mL) was added to the flask, which was sealed and stirred at 90° C. overnight. The reaction was then cooled to room temperature, diluted with DCM and directly purified by Chromatography on silica gel (0-100% ethyl acetate in hexanes) to provide 1-(5-{3-[(5-chloro-4-methylpyrimidin-2-yl)amino]-5-methylphenyl}-1,3-thiazol-2-yl)cyclobutanol (65 mg, 0.17 mmol, 44%) as a dark brown solid. MS ESI: [M+H]+ m/z 387.1 1H NMR (500 MHz, dmso) δ 9.81 (s, 1H), 8.44 (s, 1H), 7.97 (s, 1H), 7.91 (s, 1H), 7.47 (s, 1H), 7.08 (s, 1H), 6.51 (s, 1H), 2.58-2.50 (m, 2H), 2.45 (s, 3H), 2.37-2.27 (m, 5H), 1.93-1.82 (m, 2H). rhSYK activity=+++

後処理

  1. additionA flask was charged with a stir bar
  2. customThe vial was evacuated
  3. additionFully degassed tent-amyl alcohol (1.3 mL) was added to the flask, which
  4. customwas sealed
  5. temperatureThe reaction was then cooled to room temperature
  6. additiondiluted with DCM
  7. customdirectly purified by Chromatography on silica gel (0-100% ethyl acetate in hexanes)

出典と根拠

ORDレコード
ord-3dd29c3089d8459cac1fea76c1d477fb
出典データセット
uspto-grants-2013_10
特許番号
US08551984B2

反応ノート

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