Diisopropylethylamine → Methyl 5-((2,4-difluorobenzyl)carbamoyl)-1-(2,2-dimethoxyethyl)-3-methoxy-4-oxo-1,4-dihydropyridine-2-carboxylate

HRID 1505821노트

반응식

HRID 1505821 반응식
[CH3:1][O:2][CH:3]([O:21][CH3:22])[CH2:4][N:5]1[C:10]([C:11]([O:13][CH3:14])=[O:12])=[C:9]([O:15][CH3:16])[C:8](=[O:17])[C:7]([C:18]([OH:20])=O)=[CH:6]1.C(N(CC)C(C)C)(C)C.[F:32][C:33]1[CH:40]=[C:39]([F:41])[CH:38]=[CH:37][C:34]=1[CH2:35][NH2:36].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>>[F:32][C:33]1[CH:40]=[C:39]([F:41])[CH:38]=[CH:37][C:34]=1[CH2:35][NH:36][C:18]([C:7]1[C:8](=[O:17])[C:9]([O:15][CH3:16])=[C:10]([C:11]([O:13][CH3:14])=[O:12])[N:5]([CH2:4][CH:3]([O:2][CH3:1])[O:21][CH3:22])[CH:6]=1)=[O:20]

참가 물질

5

반응물 4

HCID 81531DiisopropylethylamineHCID 27332442,4-DifluorobenzylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 534690001-(2,2-Dimethoxyethyl)-5-methoxy-6-(methoxycarbonyl)-4-oxo-1,4-dihydropyridine-3-carboxylic acid

생성물 1

HCID 90311876Methyl 5-((2,4-difluorobenzyl)carbamoyl)-1-(2,2-dimethoxyethyl)-3-methoxy-4-oxo-1,4-dihydropyridine-2-carboxylate

실험 절차

1-(2,2-dimethoxyethyl)-5-methoxy-6-(methoxycarbonyl)-4-oxo-1,4-dihydropyridine-3-carboxylic acid (1-A, 0.300 g, 0.95 mmol), prepared as described in WO2011/119566 A1, was evaporated once from dry toluene, suspended in acetonitrile (4 mL) and treated with N,N-diisopropylethylamine (DIPEA) (0.329 mL, 1.90 mmol), 2,4-difluorobenzylamine (0.125 mL, 1.05 mmol) and HATU (0.433 g, 1.14 mmol). The reaction mixture was stirred for 10 minutes and concentrated. The residue was purified by flash chromatography on silica gel (10 to 60% ethyl acetate:dichloromethane) to afford the compound methyl 5-(2,4-difluorobenzylcarbamoyl)-1-(2,2-dimethoxyethyl)-3-methoxy-4-oxo-1,4-dihydropyridine-2-carboxylate, 1-B. 1H-NMR (400 MHz, DMSO-d6) δ 10.28 (t, J=6.0 Hz, 1H), 8.46 (s, 1H), 7.42 (dd, J=15.4, 8.6 Hz, 1H), 7.24 (m, 1H), 7.06 (m, 1H), 4.52 (m, 3H), 4.22 (d, J=4.4 Hz, 2H), 3.92 (s, 3H), 3.80 (s, 3H), 3.29 (d, 6H). LCMS-ESI+ (m/z): [M+H]+ calculated for C20H23F2N2O7: 441.15; found: 441.2.

후처리

  1. customwas evaporated once from dry toluene
  2. concentrationconcentrated
  3. customThe residue was purified by flash chromatography on silica gel (10 to 60% ethyl acetate:dichloromethane)

출처 및 근거

ORD 기록
ord-e6d9ae2a7fe84b38b43a214f3e892fcd
출처 데이터셋
uspto-grants-2015_12
특허 번호
US09216996B2

반응 노트

불러오는 중…