Cesium carbonate → 1-[5-(3-Chloro-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1,3-thiazol-2-yl]cyclobutanol

HRID 410503ノート

反応式

HRID 410503 の反応式
[NH2:1][C:2]1[CH:3]=[C:4]([C:9]2[S:13][C:12]([C:14]3([OH:18])[CH2:17][CH2:16][CH2:15]3)=[N:11][CH:10]=2)[CH:5]=[C:6]([Cl:8])[CH:7]=1.Cl[C:20]1[N:25]=[C:24]([C:26]([F:29])([F:28])[F:27])[CH:23]=[CH:22][N:21]=1.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+]>C(OCC)(=O)C.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.O1CCOCC1>[Cl:8][C:6]1[CH:5]=[C:4]([C:9]2[S:13][C:12]([C:14]3([OH:18])[CH2:17][CH2:16][CH2:15]3)=[N:11][CH:10]=2)[CH:3]=[C:2]([NH:1][C:20]2[N:25]=[C:24]([C:26]([F:29])([F:28])[F:27])[CH:23]=[CH:22][N:21]=2)[CH:7]=1

参加物

8

反応物 4

HCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 27739122-Chloro-4-(trifluoromethyl)pyrimidineHCID 674320031-[5-(3-Amino-5-chlorophenyl)-1,3-thiazol-2-yl]cyclobutanol

生成物 1

HCID 584563471-[5-(3-Chloro-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1,3-thiazol-2-yl]cyclobutanol収率 55.8%

試薬・触媒・溶媒 3

HCID 167845palladium(II) acetate触媒HCID 8857Ethyl Acetate溶媒HCID 312751,4-Dioxane溶媒

実験手順

The product of Step 3 (460 mg, 1.720 mmol), 2-chloro-4-(trifluoromethyl)pyrimidine (314 mg, 1.638 mmol), Xantphos (284 mg, 0.492 mmol), palladium (II) acetate (73.6 mg, 0.328 mmol), cesium carbonate (1.068 g, 3.28 mmol) and dioxane (12.3 mL) were heated at 90° C. for 90 minutes. The reaction mixture was diluted with ethyl acetate, washed with water and dried over Na2SO4. Filtration and solvent evaporation gave a residue which was further purified by column chromatography on silica gel, eluting with 40% ethyl acetate in hexane to afford 1-[5-(3-chloro-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1,3-thiazol-2-yl]cyclobutanol as a brown solid (390 mg, 55.8%). 1H NMR (500 MHz, CDCl3): δ 8.71 (d, J=4.7 Hz, 1H); 7.92 (s, 1H); 7.85 (s, 1H); 7.78 (s, 1H); 7.69 (s, 1H); 7.25 (s, 1H); 7.13 (d, J=4.8 Hz, 1H); 3.81 (s, 1H); 2.73 (s, 2H); 2.58-2.47 (m, 2H); 2.13-1.97 (m, 2H) MS APCI: [M+H]+ m/z 427.1. rhSYK activity=++

後処理

  1. washwashed with water
  2. dry with materialdried over Na2SO4
  3. filtrationFiltration and solvent evaporation
  4. customgave a residue which
  5. customwas further purified by column chromatography on silica gel
  6. washeluting with 40% ethyl acetate in hexane

出典と根拠

ORDレコード
ord-2fffe50e16f74a17a05d865ca12a5868
出典データセット
uspto-grants-2014_06
特許番号
US08759366B2

反応ノート

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