Isobutyryl chloride → Ethyl 2-(difluoromethyl)-5-(isobutyramidomethyl)nicotinate

HRID 1469796노트

반응식

HRID 1469796 반응식
C(O[C:6]([NH:8][CH2:9][C:10]1[CH:11]=[N:12][C:13]([CH:21]([F:23])[F:22])=[C:14]([CH:20]=1)[C:15]([O:17][CH2:18][CH3:19])=[O:16])=[O:7])(C)(C)C.CCN(C(C)C)[CH:27]([CH3:29])[CH3:28].C(Cl)(=O)C(C)C>Cl.CCO.CCOC(C)=O>[F:23][CH:21]([F:22])[C:13]1[N:12]=[CH:11][C:10]([CH2:9][NH:8][C:6](=[O:7])[CH:27]([CH3:29])[CH3:28])=[CH:20][C:14]=1[C:15]([O:17][CH2:18][CH3:19])=[O:16]

참가 물질

7

반응물 3

HCID 62325Isobutyryl chlorideHCID 81531DiisopropylethylamineHCID 71059899Ethyl 5-(((tert-butoxycarbonyl)amino)methyl)-2-(difluoromethyl)nicotinate

생성물 1

HCID 71059744Ethyl 2-(difluoromethyl)-5-(isobutyramidomethyl)nicotinate수율 44.1%

시약·촉매·용매 3

HCID 313Hydrochloric Acid용매HCID 702Ethanol용매HCID 8857Ethyl Acetate용매

실험 절차

A solution of ethyl 5-(((tert-butoxycarbonyl)amino)methyl)-2-(difluoromethyl)nicotinate (500 mg, 1.51 mmol) in HCl in EtOH (2 mL) was stirred at rt for 2 h. The reaction mixture was concentrated and the concentrate was dissolved in DMF (2 mL). The solution was treated with DIPEA (464 mg, 3.60 mmol) and isobutyryl chloride (115 mg, 1.08 mmol) at rt. The reaction mixture was stirred for 2 h before it was diluted with EtOAc and was washed with H2O and brine. The organic layer was separated, dried, filtered and concentrated. The residue was purified by column chromatography to afford 200 mg of the title product. 1H NMR (300 MHz, DMSO d6): δ 8.75 (s, 1H), 8.48 (t, 1H), 8.14 (s, 1H), 7.59-7.24 (t, J=54 Hz, 1H), 4.39-4.32 (m, 4H), 2.44 (m, 1H), 1.35-1.29 (t, J=6.9 Hz, 3H), 1.04-1.02 (d, J=6.9 Hz, 6H); MS [M+H]+: 301.36.

후처리

  1. concentrationThe reaction mixture was concentrated
  2. dissolutionthe concentrate was dissolved in DMF (2 mL)
  3. washwas washed with H2O and brine
  4. customThe organic layer was separated
  5. customdried
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe residue was purified by column chromatography

출처 및 근거

ORD 기록
ord-0db722cccb0445588862f4315928c95e
출처 데이터셋
uspto-grants-2015_04
특허 번호
US09006257B2

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