Triethylamine → N-[(2R)-2,3-dihydroxypropyl]-5-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1,3-thiazole-2-carboxamide

HRID 410620ノート

反応式

HRID 410620 の反応式
[NH2:1][CH2:2][C@@H:3]([OH:6])[CH2:4][OH:5].[CH3:7][C:8]1[CH:9]=[C:10]([C:25]2[S:29][C:28]([C:30](O)=[O:31])=[N:27][CH:26]=2)[CH:11]=[C:12]([NH:14][C:15]2[N:20]=[C:19]([C:21]([F:24])([F:23])[F:22])[CH:18]=[CH:17][N:16]=2)[CH:13]=1.C(N(CC)CC)C.F[P-](F)(F)(F)(F)F.N1(O[P+](N2CCCC2)(N2CCCC2)N2CCCC2)C2C=CC=CC=2N=N1>CN(C)C=O.O>[OH:6][C@@H:3]([CH2:4][OH:5])[CH2:2][NH:1][C:30]([C:28]1[S:29][C:25]([C:10]2[CH:11]=[C:12]([NH:14][C:15]3[N:20]=[C:19]([C:21]([F:24])([F:22])[F:23])[CH:18]=[CH:17][N:16]=3)[CH:13]=[C:8]([CH3:7])[CH:9]=2)=[CH:26][N:27]=1)=[O:31]

参加物

7

反応物 4

HCID 8471TriethylamineHCID 2724699PyBOPHCID 6994409(2R)-3-aminopropane-1,2-diolHCID 584562975-(3-Methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1,3-thiazole-2-carboxylic acid

生成物 1

HCID 58456310N-[(2R)-2,3-dihydroxypropyl]-5-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1,3-thiazole-2-carboxamide収率 82%

試薬・触媒・溶媒 2

HCID 962Water溶媒HCID 6228Dimethylformamide溶媒

実験手順

To a solution of (2R)-3-aminopropane-1,2-diol (132 mg, 1.446 mmol), 5-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1,3-thiazole-2-carboxylic acid (500 mg, 1.315 mmol), and triethylamine (0.403 mL, 2.89 mmol) in N,N-dimethylformamide (8 mL) was added benzotriazol-1-yl-oxytripyrrolidinophosphonium hexafluorophosphate (821 mg, 1.578 mmol). After 45 minutes, water (32 mL) was added to the reaction mixture and the resulting yellow solid was collected by filtration; the solid was then purified by trituration using a mixture of methanol (2 mL), ethyl acetate (3 mL), and dichloromethane (3 mL) followed by filtration and drying in vacuo. The mother liqour from the trituration was concentrated and additional product was purified via column chromatography on silica (Biotage 50 g SNAP column, 97.5:2.5 to 85:15 dichloromethane:methanol). The combined material afforded in N-[(2R)-2,3-dihydroxypropyl]-5-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1,3-thiazole-2-carboxamide (487 mg 82% yield) as a yellow solid. MS ESI: [M+H]+ m/z 454.0. 1H NMR (500 MHz, d6-DMSO): δ 10.31 (s, 1H); 8.85 (d, J=4.9 Hz, 1H); 8.53 (t, J=5.9 Hz, 1H); 8.29 (s, 1H); 8.11 (s, 1H); 7.51 (s, 1H); 7.31 (s, 1H); 7.30 (d, J=4.9 Hz, 1H); 4.90 (d, J=5.1 Hz, 1H); 4.64 (t, J=5.7 Hz, 1H); 3.63 (m, 1H); 3.42 (m, 1H); 3.35 (m, 2H); 3.23 (m, 1H); 2.34 (s, 3H). rhSYK activity=+++

後処理

  1. filtrationthe resulting yellow solid was collected by filtration
  2. customthe solid was then purified by trituration
  3. additiona mixture of methanol (2 mL), ethyl acetate (3 mL), and dichloromethane (3 mL)
  4. filtrationfollowed by filtration
  5. customdrying in vacuo
  6. concentrationThe mother liqour from the trituration was concentrated
  7. customadditional product was purified via column chromatography on silica (Biotage 50 g SNAP column, 97.5:2.5 to 85:15 dichloromethane:methanol)

出典と根拠

ORDレコード
ord-19e3d99cc2114704ae313cf7e32286c1
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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