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 348200ノート

反応式

HRID 348200 の反応式
[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

参加物

7

反応物 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

生成物 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-carboxamide収率 72.6%

試薬・触媒・溶媒 3

HCID 178418397HCID 178418397、化合物触媒HCID 962Water溶媒HCID 6342Acetonitrile溶媒

反応条件

温度
90 °C

実験手順

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.

後処理

  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

出典と根拠

ORDレコード
ord-0709aef3f5e74267ba43ba7b2d192b08
出典データセット
uspto-grants-2007_02
特許番号
US07176196B2

反応ノート

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