Potassium Fluoride → 1-{5-[3-(Trifluoromethyl)-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl]-1,3-thiazol-2-yl}cyclobutanol

HRID 1039992ノート

反応式

HRID 1039992 の反応式
C(P(C12CC3CC(CC(C3)C1)C2)C12CC3CC(CC(C3)C1)C2)CCC.CC1(C)C(C)(C)OB([C:34]2[CH:35]=[C:36]([NH:44][C:45]3[N:50]=[C:49]([C:51]([F:54])([F:53])[F:52])[CH:48]=[CH:47][N:46]=3)[CH:37]=[C:38]([C:40]([F:43])([F:42])[F:41])[CH:39]=2)O1.Br[C:57]1[S:61][C:60]([C:62]2([OH:66])[CH2:65][CH2:64][CH2:63]2)=[N:59][CH:58]=1.[F-].[K+]>C1COCC1.C(OCC)(=O)C.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.O>[F:43][C:40]([F:42])([F:41])[C:38]1[CH:39]=[C:34]([C:57]2[S:61][C:60]([C:62]3([OH:66])[CH2:65][CH2:64][CH2:63]3)=[N:59][CH:58]=2)[CH:35]=[C:36]([NH:44][C:45]2[N:50]=[C:49]([C:51]([F:52])([F:54])[F:53])[CH:48]=[CH:47][N:46]=2)[CH:37]=1

参加物

9

反応物 4

HCID 522689Potassium FluorideHCID 11371790Bis(adamantan-1-yl)(butyl)phosphaneHCID 584562241-(5-Bromothiazol-2-yl)cyclobutanolHCID 58456333N-(3-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-5-(trifluoromethyl)phenyl)-4-(trifluoromethyl)pyrimidin-2-amine

生成物 1

HCID 584562341-{5-[3-(Trifluoromethyl)-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl]-1,3-thiazol-2-yl}cyclobutanol収率 86.2%

試薬・触媒・溶媒 4

HCID 167845palladium(II) acetate触媒HCID 962Water溶媒HCID 8028Tetrahydrofuran溶媒HCID 8857Ethyl Acetate溶媒

反応条件

温度
85 °C

実験手順

A solution of palladium(II) acetate (2.55 mg, 0.011 mmol) and butyldi-1-adamantyl phosphine (CataCXium A, 8.14 mg, 0.023 mmol) in THF (1.42 mL) was stirred for 10 min while nitrogen was bubbled through gently. Intermediate 13 (100 mg, 0.189 mmol), Intermediate 1 (51.0 mg, 0.218 mmol), potassium fluoride (33.0 mg, 0.568 mmol) and water (473 μl) were added. The tube was sealed (screw cap) and heated overnight at 85° C. The reaction was cooled to room temperature and diluted with ethyl acetate. After decanting the solids and extraction with ethyl acetate, the organic layer was washed with brine and dried over MgSO4. Filtration and subsequent solvent evaporation gave a residue which was purified by chromatography on silica gel (5-50% ethyl acetate in hexanes) to give 75 mg (86%) of 1-{5-[3-(trifluoromethyl)-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl]-1,3-thiazol-2-yl}cyclobutanol as a grey solid. MS ESI [M+H]+ 461.1. 1H NMR (400 MHz, DMSO-d6): δ 10.67 (s, 1H); 8.93 (d, J=4.9 Hz, 1H); 8.33 (s, 1H); 8.24 (s, 1H); 8.17 (s, 1H); 7.68 (s, 1H); 7.41 (d, J=4.9 Hz, 1H); 6.62 (s, 1H); 2.59-2.48 (m, 2H); 2.42-2.31 (m, 2H); 1.98-1.87 (m, 2H). rhSYK activity=++

後処理

  1. customwas bubbled through gently
  2. customThe tube was sealed
  3. custom(screw cap)
  4. temperatureThe reaction was cooled to room temperature
  5. customAfter decanting
  6. extractionthe solids and extraction with ethyl acetate
  7. washthe organic layer was washed with brine
  8. dry with materialdried over MgSO4
  9. filtrationFiltration and subsequent solvent evaporation
  10. customgave a residue which
  11. customwas purified by chromatography on silica gel (5-50% ethyl acetate in hexanes)

出典と根拠

ORDレコード
ord-d350f240eb504a4fbfdac962a3cae897
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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