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

HRID 2272443ノート

反応式

HRID 2272443 の反応式
[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

参加物

6

反応物 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

生成物 1

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

試薬・触媒・溶媒 1

HCID 887Methanol溶媒

実験手順

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]+.

後処理

  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

出典と根拠

ORDレコード
ord-8ca1484f798940bda173b4f10b3cfc1e
出典データセット
uspto-grants-2015_09
特許番号
US09120761B2

反応ノート

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