反応 #679549

反応方程式

Formaldehyde

1-(2-(2-(2-((4-(piperidin-4-yl)phenyl)amino)-5-(trifluoromethyl)pyrimidin-4-yl)ethyl)phenyl)cyclopropanecarboxamide

1-(2-(2-(2-((4-(Piperidin-4-yl)phenyl)amino)-5-(trifluoromethyl)pyrimidin-4-yl)ethyl)phenyl)cyclopropanecarboxamide

sodium triacetoxyborohydride

→

title compound 3

収率 88.1%

1-(2-(2-(2-((4-(1-methylpiperidin-4-yl)phenyl)amino)-5-(trifluoromethyl)pyrimidin-4-yl)ethyl)phenyl)cyclopropanecarboxamide

収率 88.1%

溶媒

MeOH

反応条件

後処理

1. 1
   workup.STIRRINGstirring
2. 2
   workup.WAITcontinued for 2.5 hours
3. 3
   その他The volatiles were removed in vacuo
4. 4
   workup.ADDITIONthe residue was diluted with EtOAc (20 mL) and saturated aqueous NaHCO3 (20 mL)
5. 5
   その他The layers were separated
6. 6
   抽出the aqueous layer was extracted with EtOAc (2×20 mL)
7. 7
   洗浄The combined organic layers were washed with brine (20 mL)
8. 8
   乾燥dried over MgSO4
9. 9
   その他the volatiles were removed under reduced pressure
10. 10
    workup.DISSOLUTIONThe residue was dissolved in DCM (1 mL) to which cyclohexane (5 mL)
11. 11
    workup.ADDITIONwas added
12. 12
    その他to form a cloudy suspension
13. 13
    その他The solvent was removed in vacuo
14. 14
    その他the resulting solid was dried under high vacuum

実験手順

Formaldehyde (37 wt % in H2O; 8.8 μL, 0.12 mmol) was added to a solution of 1-(2-(2-(2-((4-(piperidin-4-yl)phenyl)amino)-5-(trifluoromethyl)pyrimidin-4-yl)ethyl)phenyl)cyclopropanecarboxamide (2) (20 mg, 39 μmol) in MeOH (5.0 mL) under an atmosphere of nitrogen. The resulting mixture was stirred for 10 minutes at room temperature then sodium triacetoxyborohydride (33 mg, 0.16 mmol) was added in one portion and stirring continued for 2.5 hours. The volatiles were removed in vacuo and the residue was diluted with EtOAc (20 mL) and saturated aqueous NaHCO3 (20 mL). The layers were separated and the aqueous layer was extracted with EtOAc (2×20 mL). The combined organic layers were washed with brine (20 mL), dried over MgSO4 and the volatiles were removed under reduced pressure. The residue was dissolved in DCM (1 mL) to which cyclohexane (5 mL) was added to form a cloudy suspension. The solvent was removed in vacuo and the resulting solid was dried under high vacuum to give the title compound 3 as a white powder (18 mg, 88%); 1H NMR (400 MHz, d6-DMSO) δ 10.15 (s, 1H), 8.67 (s, 1H), 7.66 (d, J=8.5 Hz, 2H), 7.40-7.27 (m, 3H), 7.22 (dd, J=14.4, 8.0 Hz, 3H), 6.99 (s, 1H), 6.01 (s, 1H), 3.21-3.05 (m, 4H), 2.88 (d, J=10.9 Hz, 2H), 2.50-2.30 (m, 1H), 2.21 (s, 3H), 1.99 (s, 2H), 1.79-1.58 (m, 4H), 1.44 (s, 2H), 0.97 (s, 2H). LCMS-A: 5.028 min; m/z 524 [M+H]+.

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