Hydrochloric Acid → 4-Hydroxy-4-[5-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1,3-thiazol-2-yl]piperidine-1-carboxamide

HRID 410560ノート

反応式

HRID 410560 の反応式
[CH3:1][C:2]1[CH:3]=[C:4]([C:19]2[S:23][C:22]([C:24]3([OH:30])[CH2:29][CH2:28][NH:27][CH2:26][CH2:25]3)=[N:21][CH:20]=2)[CH:5]=[C:6]([NH:8][C:9]2[N:14]=[C:13]([C:15]([F:18])([F:17])[F:16])[CH:12]=[CH:11][N:10]=2)[CH:7]=1.[O-:31][C:32]#[N:33].[K+].Cl>C1COCC1.O.C([O-])(O)=O.[Na+]>[OH:30][C:24]1([C:22]2[S:23][C:19]([C:4]3[CH:5]=[C:6]([NH:8][C:9]4[N:14]=[C:13]([C:15]([F:17])([F:18])[F:16])[CH:12]=[CH:11][N:10]=4)[CH:7]=[C:2]([CH3:1])[CH:3]=3)=[CH:20][N:21]=2)[CH2:25][CH2:26][N:27]([C:32]([NH2:33])=[O:31])[CH2:28][CH2:29]1

参加物

6

反応物 3

HCID 313Hydrochloric Acid2 回HCID 11378442Potassium cyanate2 回HCID 584561264-[5-(3-Methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1,3-thiazol-2-yl]piperidin-4-ol

生成物 1

HCID 584562314-Hydroxy-4-[5-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1,3-thiazol-2-yl]piperidine-1-carboxamide収率 73.5%

試薬・触媒・溶媒 2

HCID 516892Sodium Bicarbonate溶媒HCID 21881883Oxolane--water (1/1)溶媒

反応条件

温度
50 °C

実験手順

To 15 mg (0.034 mmol) of 4-[5-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}-phenyl)-1,3-thiazol-2-yl]piperidin-4-ol in THF/Water (3:1, 1 mL) was added 4.2 mg (0.052 mmol, 1.5 eq) of potassium cyanate and 2N hydrochloric acid (22 μL, 1.3 eq). The mixture was heated at 50° C. for 6 h and then another 1.5 eq of potassium cyanate and 1.5 eq HCl added and the mixture stirred at 50° C. overnight. The reaction was diluted with saturated aqueous NaHCO3 and was partitioned with ethyl acetate. The organic layer was washed with water and dried, filtered and solvent removed under reduced pressure. The residue was purified by column chromatography on silica gel (0-100% ethyl acetate in hexanes) to give 12 mg (0.025 mmol, 73%) of 4-hydroxy-4-[5-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1,3-thiazol-2-yl]piperidine-1-carboxamide as off-white solid. MS ESI: [M+H]+ m/z 479.2. 1H NMR (600 MHz, CD3OD): δ 8.68 (d, J=4.8 Hz, 1H); 7.99 (s, 1H); 7.87 (s, 1H); 7.40 (s, 1H); 7.10 (m, 2H); 3.91 (m, \2H); 3.28 (m, 2H); 2.34 (s, 3H); 2.16 (m, 2H); 1.83 (m, 2H). rhSYK activity=+++

後処理

  1. customwas partitioned with ethyl acetate
  2. washThe organic layer was washed with water
  3. customdried
  4. filtrationfiltered
  5. customsolvent removed under reduced pressure
  6. customThe residue was purified by column chromatography on silica gel (0-100% ethyl acetate in hexanes)

出典と根拠

ORDレコード
ord-edce0a0e80104b93bbf4a61a915b7504
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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