Sodium Carbonate → N-(4-Fluoro-2-(2-methoxypyridin-3-yl)benzyl)-3-(benzyloxy)-9,9-dimethyl-4-oxo-4,6,7,9-tetrahydropyrimido[2,1-c][1,4]oxazine-2-carboxamide

HRID 348200노트

반응식

HRID 348200 반응식
[F:1][C:2]1[CH:32]=[CH:31][C:5]([CH2:6][NH:7][C:8]([C:10]2[N:11]=[C:12]3[N:17]([C:18](=[O:28])[C:19]=2[O:20][CH2:21][C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)[CH2:16][CH2:15][O:14][C:13]3([CH3:30])[CH3:29])=[O:9])=[C:4](I)[CH:3]=1.[CH3:34][O:35][C:36]1[C:41](B(O)O)=[CH:40][CH:39]=[CH:38][N:37]=1.C(=O)([O-])[O-].[Na+].[Na+]>C(#N)C.O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[F:1][C:2]1[CH:32]=[CH:31][C:5]([CH2:6][NH:7][C:8]([C:10]2[N:11]=[C:12]3[N:17]([C:18](=[O:28])[C:19]=2[O:20][CH2:21][C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)[CH2:16][CH2:15][O:14][C:13]3([CH3:30])[CH3:29])=[O:9])=[C:4]([C:41]2[C:36]([O:35][CH3:34])=[N:37][CH:38]=[CH:39][CH:40]=2)[CH:3]=1

참가 물질

7

반응물 3

HCID 10340Sodium CarbonateHCID 2762709(2-Methoxypyridin-3-yl)boronic acidHCID 21070019N-(4-fluoro-2-iodobenzyl)-3-(benzyloxy)-9,9-dimethyl-4-oxo-4,6,7,9-tetrahydropyrimido[2,1-c][1,4]oxazine-2-carboxamide

생성물 1

HCID 21069999N-(4-Fluoro-2-(2-methoxypyridin-3-yl)benzyl)-3-(benzyloxy)-9,9-dimethyl-4-oxo-4,6,7,9-tetrahydropyrimido[2,1-c][1,4]oxazine-2-carboxamide수율 72.6%

시약·촉매·용매 3

HCID 178418397HCID 178418397, 화합물촉매HCID 962Water용매HCID 6342Acetonitrile용매

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온도
90 °C

실험 절차

Intermediate 174, N-(4-fluoro-2-iodobenzyl)-3-(benzyloxy)-9,9-dimethyl-4-oxo-4,6,7,9-tetrahydropyrimido[2,1-c][1,4]oxazine-2-carboxamide (0.350 g, 0.62 mmol) in a mixture of acetonitrile (12 ml) and water (12 ml) was treated with 2-methoxypyridin-3-ylboronic acid (0.190 g, 1.24 mmol), sodium carbonate (0.20 g, 1.88 mmol) and tetrakis(triphenylphosphine)palladium(0) (0.15 g). The reaction mixture was degassed, flushed with argon and heated at 90° C. for 30 min. The reaction mixture was then diluted with ethyl acetate, washed with water and brine, dried over anhydrous magnesium sulfate and concentrated. Chromatography of the residue on silica gel (elution gradient of ethyl acetate in hexane) gave 0.245 g (72% yield) of the title material as a white solid. 1HNMR 400 MHz (CDCl3) δ ppm: 1.63 (6H, s, 2×CH3), 3.89 (3H, s, OCH3), 4.04 (4H, m, 2×CH2), 4.37 (2H, broad, NCH2), 5.26 (2H, s, OCH2), 6.93 (1H, dd, J=2.5 Hz and J=9 Hz, aromatic), 7.0 (1H, dd, J=5 Hz and J=7 Hz, aromatic), 7.06 (1H, m, aromatic), 7.3–7.5 (8H, m, aromatics and NH), 8.24 (1H, m, aromatic). HRMS (ESI+) calculated for C30H30FN4O5 [M+H+]: 545.2200. Found: 545.2184.

후처리

  1. customThe reaction mixture was degassed
  2. customflushed with argon
  3. additionThe reaction mixture was then diluted with ethyl acetate
  4. washwashed with water and brine
  5. dry with materialdried over anhydrous magnesium sulfate
  6. concentrationconcentrated

출처 및 근거

ORD 기록
ord-0709aef3f5e74267ba43ba7b2d192b08
출처 데이터셋
uspto-grants-2007_02
특허 번호
US07176196B2

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