Formaldehyde → Methyl 2-(2-(2-(2-((2-methyl-4-(1-methylpiperidin-4-yl)phenyl)amino)-5-(trifluoromethyl)pyrimidin-4-yl)ethyl)phenyl)acetate

HRID 705777노트

반응식

HRID 705777 반응식
[CH3:1][C:2]1[CH:7]=[C:6]([CH:8]2[CH2:13][CH2:12][NH:11][CH2:10][CH2:9]2)[CH:5]=[CH:4][C:3]=1[NH:14][C:15]1[N:20]=[C:19]([CH2:21][CH2:22][C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][C:24]=2[CH2:29][C:30]([O:32][CH3:33])=[O:31])[C:18]([C:34]([F:37])([F:36])[F:35])=[CH:17][N:16]=1.C=O.[C:40](O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C(OCC)(=O)C>CO>[CH3:1][C:2]1[CH:7]=[C:6]([CH:8]2[CH2:9][CH2:10][N:11]([CH3:40])[CH2:12][CH2:13]2)[CH:5]=[CH:4][C:3]=1[NH:14][C:15]1[N:20]=[C:19]([CH2:21][CH2:22][C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][C:24]=2[CH2:29][C:30]([O:32][CH3:33])=[O:31])[C:18]([C:34]([F:37])([F:35])[F:36])=[CH:17][N:16]=1

참가 물질

6

반응물 4

HCID 712FormaldehydeHCID 8857Ethyl AcetateHCID 5049666Sodium triacetoxyborohydrideHCID 68283581Methyl 2-(2-(2-(2-((2-methyl-4-(piperidin-4-yl)phenyl)amino)-5-(trifluoromethyl)pyrimidin-4-yl)ethyl)phenyl)acetate

생성물 1

HCID 68282776Methyl 2-(2-(2-(2-((2-methyl-4-(1-methylpiperidin-4-yl)phenyl)amino)-5-(trifluoromethyl)pyrimidin-4-yl)ethyl)phenyl)acetate

시약·촉매·용매 1

HCID 887Methanol용매

실험 절차

Methyl 2-(2-(2-(2-((2-methyl-4-(piperidin-4-yl)phenyl)amino)-5-(trifluoromethyl)pyrimidin-4-yl)ethyl)phenyl)acetate (54) (1.10 g, 2.15 mmol) was dissolved in dry MeOH (20 mL) and formaldehyde solution (37% aq; 348 μL, 4.29 mmol) was added. Sodium triacetoxyborohydride (2.27 g, 10.7 mmol) was added under nitrogen and the resultant mixture was stirred at room temperature for 16 hours. Ethyl acetate (50 mL) was added and the mixture was washed with 10% NaHCO3 solution (20 mL). The organic layer was separated, dried (MgSO4) then the volatiles removed by evaporation under reduced pressure. Chromatography (SiO2, 0-50% MeOH/DCM) gave the title compound (I55) (480 mg, 42%) as a cream solid; 1H NMR (400 MHz, CDCl3) δ 8.54 (s, 1H), 7.83-7.73 (m, 1H), 7.35 (s, 1H), 7.32-7.19 (m, 3H), 7.19-7.09 (m, 2H), 7.07-6.97 (m, 1H), 3.76 (s, 2H), 3.70 (s, 3H), 3.23 (d, J=11.5 Hz, 2H), 3.17-3.04 (m, 4H), 2.61-2.51 (m, 1H), 2.50 (s, 3H), 2.35 (s, 3H), 2.33-2.24 (m, 2H), 2.02-1.84 (m, 4H). LCMS Method C: rt 5.25 min; m/z 527.2 [M+1]+.

후처리

  1. washthe mixture was washed with 10% NaHCO3 solution (20 mL)
  2. customThe organic layer was separated
  3. dry with materialdried (MgSO4)
  4. customthe volatiles removed by evaporation under reduced pressure

출처 및 근거

ORD 기록
ord-7a308b1282c2458eac16f03b8b50b123
출처 데이터셋
uspto-grants-2015_11
특허 번호
US09174946B2

반응 노트

불러오는 중…