Propylphosphonic anhydride → 2-(4-(5-ethoxy-6-((4-methoxybenzyl)oxy)pyridin-3-yl)-2-fluorophenyl)-N-(3-(1-methyl-1H-pyrazol-4-yl)-5-(trifluoromethyl)phenyl)acetamide

HRID 1050194노트

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HRID 1050194 반응식
[CH2:1]([O:3][C:4]1[CH:5]=[C:6]([C:20]2[CH:25]=[CH:24][C:23]([CH2:26][C:27]([OH:29])=O)=[C:22]([F:30])[CH:21]=2)[CH:7]=[N:8][C:9]=1[O:10][CH2:11][C:12]1[CH:17]=[CH:16][C:15]([O:18][CH3:19])=[CH:14][CH:13]=1)[CH3:2].[CH3:31][N:32]1[CH:36]=[C:35]([C:37]2[CH:38]=[C:39]([CH:41]=[C:42]([C:44]([F:47])([F:46])[F:45])[CH:43]=2)[NH2:40])[CH:34]=[N:33]1.C(P1(=O)OP(CCC)(=O)OP(CCC)(=O)O1)CC>N1C=CC=CC=1>[CH2:1]([O:3][C:4]1[CH:5]=[C:6]([C:20]2[CH:25]=[CH:24][C:23]([CH2:26][C:27]([NH:40][C:39]3[CH:41]=[C:42]([C:44]([F:45])([F:46])[F:47])[CH:43]=[C:37]([C:35]4[CH:34]=[N:33][N:32]([CH3:31])[CH:36]=4)[CH:38]=3)=[O:29])=[C:22]([F:30])[CH:21]=2)[CH:7]=[N:8][C:9]=1[O:10][CH2:11][C:12]1[CH:17]=[CH:16][C:15]([O:18][CH3:19])=[CH:14][CH:13]=1)[CH3:2]

참가 물질

5

반응물 3

HCID 111923Propylphosphonic anhydrideHCID 904166242-(4-(5-Ethoxy-6-((4-methoxybenzyl)oxy)pyridin-3-yl)-2-fluorophenyl) acetic acidHCID 904234893-(1-methyl-1H-pyrazol-4-yl)-5-(trifluoromethyl)aniline

생성물 1

HCID 904233112-(4-(5-ethoxy-6-((4-methoxybenzyl)oxy)pyridin-3-yl)-2-fluorophenyl)-N-(3-(1-methyl-1H-pyrazol-4-yl)-5-(trifluoromethyl)phenyl)acetamide수율 89.3%

시약·촉매·용매 1

HCID 1049Pyridine용매

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온도
27 °C

실험 절차

To a solution of 2-(4-(5-ethoxy-6-((4-methoxybenzyl)oxy)pyridin-3-yl)-2-fluorophenyl)acetic acid (100 mg, 0.243 mmol) and 3-(1-methyl-1H-pyrazol-4-yl)-5-(trifluoromethyl)aniline (58.6 mg, 0.243 mmol) in pyridine (2 mL) was added T3P® (0.5 mL, 0.243 mmol) at 27° C. under N2. The mixture was stirred at 27° C. for 30 min. LCMS showed the reaction was completed. Then the mixture was put onto ice (5 g). The mixture was concentrated to give the residue. The residue was purified by preparative TLC (DCM/MeOH=10:1, Rf=0.6) to yield a light yellow solid of 2-(4-(5-ethoxy-6-((4-methoxybenzyl)oxy)pyridin-3-yl)-2-fluorophenyl)-N-(3-(1-methyl-1H-pyrazol-4-yl)-5-(trifluoromethyl)phenyl)acetamide (138 mg, 0.217 mmol, 89% yield): 1H NMR (400 MHz, CD3OD) δ 8.09-7.93 (m, 2H), 7.87-7.76 (m, 2H), 7.69-7.52 (m, 2H), 7.49-7.33 (m, 4H), 7.23 (dd, J=7.8, 16.4 Hz, 2H), 6.91 (d, J=7.9 Hz, 1H), 6.72 (d, J=8.4 Hz, 1H), 5.38-5.15 (m, 2H), 4.15 (d, J=7.1 Hz, 2H), 3.94-3.60 (m, 8H), 1.42 (t, J=6.8 Hz, 3H). ES-LCMS m/z 635 (M+H).

후처리

  1. concentrationThe mixture was concentrated
  2. customto give the residue
  3. customThe residue was purified by preparative TLC (DCM/MeOH=10:1, Rf=0.6)

출처 및 근거

ORD 기록
ord-8c7d933e99bf49c086a529e657c0f34c
출처 데이터셋
uspto-grants-2016_07
특허 번호
US09382238B2

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