Pyridine → N-(4-(2-acetamidopyridin-4-yloxy)-2-fluorophenyl)-N'-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide

HRID 476376노트

반응식

HRID 476376 반응식
[NH2:1][C:2]1[CH:7]=[C:6]([O:8][C:9]2[CH:14]=[CH:13][C:12]([NH:15][C:16]([C:18]3([C:21]([NH:23][C:24]4[CH:29]=[CH:28][C:27]([F:30])=[CH:26][CH:25]=4)=[O:22])[CH2:20][CH2:19]3)=[O:17])=[C:11]([F:31])[CH:10]=2)[CH:5]=[CH:4][N:3]=1.N1C=CC=CC=1.[C:38](OC(=O)C)(=[O:40])[CH3:39]>C(Cl)Cl>[C:38]([NH:1][C:2]1[CH:7]=[C:6]([O:8][C:9]2[CH:14]=[CH:13][C:12]([NH:15][C:16]([C:18]3([C:21]([NH:23][C:24]4[CH:25]=[CH:26][C:27]([F:30])=[CH:28][CH:29]=4)=[O:22])[CH2:20][CH2:19]3)=[O:17])=[C:11]([F:31])[CH:10]=2)[CH:5]=[CH:4][N:3]=1)(=[O:40])[CH3:39]

참가 물질

5

반응물 3

HCID 1049PyridineHCID 7918Acetic AnhydrideHCID 59596943N-(4-(2-aminopyridin-4-yloxy)-2-fluorophenyl)-N'-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide

생성물 1

HCID 66604602N-(4-(2-acetamidopyridin-4-yloxy)-2-fluorophenyl)-N'-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide수율 70.4%

시약·촉매·용매 1

HCID 6344Dichloromethane용매

실험 절차

A solution of N-(4-(2-aminopyridin-4-yloxy)-2-fluorophenyl)-N′-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide (61 mg, 0.14 mmol) in CH2Cl2 (3 mL) was treated with pyridine (0.058 mL, 0.72 mmol) and acetic anhydride (0.13 mL, 1.4 mmol). The resultant mixture was stirred at RT for 2 days. The reaction was quenched with saturated aqueous NaHCO3 and was further stirred for 2 h. The mixture was diluted with EtOAc (30 mL) and was washed with saturated aqueous NaHCO3 (20 mL), water (20 mL) and brine (20 mL). The mixture was concentrated in vacuo and purified by silica gel chromatography to provide N-(4-(2-acetamidopyridin-4-yloxy)-2-fluorophenyl)-N′-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide (46 mg, 69% yield). 1H NMR (400 MHz, DMSO-d6): δ10.56 (s, 1H), 10.54 (s, 1H), 9.96 (s, 1H), 8.18 (d, J=5.8 Hz, 1H), 7.92 (t, 1H), 7.65 (d, J=1.9 Hz, 1H) 7.59 (m, 2H), 7.24 (dd, J=11.2, 2.5 Hz, 1H), 7.15 (m, 2H), 7.01 (m, 1H), 6.68 (dd, J=5.7, 2.3 Hz, 1H), 2.02 (s, 3H), 1.60-1.52 (m, 4H); MS (ESI) m/z: 467.2 (M+H+).

후처리

  1. customThe reaction was quenched with saturated aqueous NaHCO3
  2. additionThe mixture was diluted with EtOAc (30 mL)
  3. washwas washed with saturated aqueous NaHCO3 (20 mL), water (20 mL) and brine (20 mL)
  4. concentrationThe mixture was concentrated in vacuo
  5. custompurified by silica gel chromatography

출처 및 근거

ORD 기록
ord-77f980be3c6c4ed9b3e974816d277046
출처 데이터셋
uspto-grants-2014_01
특허 번호
US08637672B2

반응 노트

불러오는 중…