Trifluoroacetic acid → 2-(2-(2-(2-((4-(Piperidin-4-yl)phenyl)amino)-5-(trifluoromethyl)pyrimidin-4-yl)ethyl)pyridin-3-yl)acetamide

HRID 1473148ノート

反応式

HRID 1473148 の反応式
FC(F)(F)C(O)=O.[NH2:8][C:9](=[O:49])[CH2:10][C:11]1[C:12]([CH2:17][CH2:18][C:19]2[C:24]([C:25]([F:28])([F:27])[F:26])=[CH:23][N:22]=[C:21]([NH:29][C:30]3[CH:35]=[CH:34][C:33]([CH:36]4[CH2:41][CH2:40][N:39](C(OC(C)(C)C)=O)[CH2:38][CH2:37]4)=[CH:32][CH:31]=3)[N:20]=2)=[N:13][CH:14]=[CH:15][CH:16]=1>C(Cl)Cl.C1CCCCC1>[NH:39]1[CH2:40][CH2:41][CH:36]([C:33]2[CH:34]=[CH:35][C:30]([NH:29][C:21]3[N:20]=[C:19]([CH2:18][CH2:17][C:12]4[C:11]([CH2:10][C:9]([NH2:8])=[O:49])=[CH:16][CH:15]=[CH:14][N:13]=4)[C:24]([C:25]([F:28])([F:26])[F:27])=[CH:23][N:22]=3)=[CH:31][CH:32]=2)[CH2:37][CH2:38]1

参加物

5

反応物 2

HCID 6422Trifluoroacetic acidHCID 71209188tert-Butyl 4-(4-((4-(2-(3-(2-amino-2-oxoethyl)pyridin-2-yl)ethyl)-5-(trifluoromethyl)pyrimidin-2-yl)amino)phenyl)piperidine-1-carboxylate

生成物 1

HCID 601648082-(2-(2-(2-((4-(Piperidin-4-yl)phenyl)amino)-5-(trifluoromethyl)pyrimidin-4-yl)ethyl)pyridin-3-yl)acetamide収率 66.6%

試薬・触媒・溶媒 2

HCID 6344Dichloromethane溶媒2 回HCID 8078Cyclohexane溶媒

実験手順

Trifluoroacetic acid (0.337 mL, 4.40 mmol) was added to a solution tert-butyl 4-(4-((4-(2-(3-(2-amino-2-oxoethyl)pyridin-2-yl)ethyl)-5-(trifluoromethyl)pyrimidin-2-yl)amino)phenyl)piperidine-1-carboxylate (I124) (64.3 mg, 0.110 mmol) in dry DCM (15 mL) under an atmosphere of nitrogen and the reaction was stirred at room temperature for 23 hours. The volatiles were removed in vacuo and the residue partitioned between EtOAc (40 mL) and 2 M NaOH (50 mL). The layers were separated and the aqueous layer was extracted with EtOAc (2×30 mL). The combined organic layers were washed with water (40 mL), brine (40 mL) and dried over Na2SO4. After filtration the solvent was removed under reduced pressure to give a yellow solid which was suspended in DCM (5 mL) and cyclohexane (15 mL). The precipitate was filtered to afford the title compound (32) (35.5 mg, 53%) as yellow solid; 1H NMR (400 MHz, d6-DMSO) δ 10.05 (s, 1H), 8.64 (s, 1H), 8.36 (dd, J=4.8, 1.7 Hz, 1H), 7.62-7.55 (m, 3H), 7.53 (s, 1H), 7.18 (dd, J=7.6, 4.8 Hz, 1H), 7.15 (d, J=8.6 Hz, 2H), 7.00 (s, 1H), 3.53 (s, 2H), 3.24 (s, 4H), 3.02 (d, J=11.9 Hz, 2H), 2.61-2.52 (m, peaks obscured by solvent), 1.67 (d, J=11.3 Hz, 2H), 1.49 (qd, J=12.2, 3.8 Hz, 2H). LCMS Method C: rt 1.50, 1.59 min; m/z 485 [M+H]+.

後処理

  1. customThe volatiles were removed in vacuo
  2. customthe residue partitioned between EtOAc (40 mL) and 2 M NaOH (50 mL)
  3. customThe layers were separated
  4. extractionthe aqueous layer was extracted with EtOAc (2×30 mL)
  5. washThe combined organic layers were washed with water (40 mL), brine (40 mL)
  6. dry with materialdried over Na2SO4
  7. filtrationAfter filtration the solvent
  8. customwas removed under reduced pressure
  9. customto give a yellow solid which
  10. filtrationThe precipitate was filtered

出典と根拠

ORDレコード
ord-045427cf0b6e45cdb4504b62e482bcbe
出典データセット
uspto-grants-2015_04
特許番号
US09012461B2

反応ノート

読み込み中…