Potassium Bicarbonate → n-(2-(3-Bromoisoxazol-5-yl)-4-fluorobenzyl)-3-(benzyloxy)-9,9-dimethyl-4-oxo-4,6,7,9-tetrahydropyrimido[2,1-c][1,4]oxazine-2-carboxamide

HRID 348206ノート

反応式

HRID 348206 の反応式
[C:1]([C:3]1[CH:33]=[C:32]([F:34])[CH:31]=[CH:30][C:4]=1[CH2:5][NH:6][C:7]([C:9]1[N:10]=[C:11]2[N:16]([C:17](=[O:27])[C:18]=1[O:19][CH2:20][C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1)[CH2:15][CH2:14][O:13][C:12]2([CH3:29])[CH3:28])=[O:8])#[CH:2].C(=O)(O)[O-].[K+].[Br:40][C:41](Br)=[N:42][OH:43]>C(OCC)(=O)C.O>[Br:40][C:41]1[CH:2]=[C:1]([C:3]2[CH:33]=[C:32]([F:34])[CH:31]=[CH:30][C:4]=2[CH2:5][NH:6][C:7]([C:9]2[N:10]=[C:11]3[N:16]([C:17](=[O:27])[C:18]=2[O:19][CH2:20][C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)[CH2:15][CH2:14][O:13][C:12]3([CH3:29])[CH3:28])=[O:8])[O:43][N:42]=1

参加物

6

反応物 3

HCID 516893Potassium Bicarbonate2 回HCID 27632191-bromo-N-hydroxymethanecarbonimidoyl bromide2 回HCID 21069992N-(2-Ethynyl-4-fluorobenzyl)-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 21069977n-(2-(3-Bromoisoxazol-5-yl)-4-fluorobenzyl)-3-(benzyloxy)-9,9-dimethyl-4-oxo-4,6,7,9-tetrahydropyrimido[2,1-c][1,4]oxazine-2-carboxamide収率 68%

試薬・触媒・溶媒 2

HCID 962Water溶媒HCID 8857Ethyl Acetate溶媒2 回

反応条件

温度
22 °C

実験手順

A solution of intermediate 179, N-(2-ethynyl-4-fluorobenzyl)-3-(benzyloxy)-9,9-dimethyl-4-oxo-4,6,7,9-tetrahydropyrimido[2,1-c][1,4]oxazine-2-carboxamide (0.350 g, 0.76 mmol) in a mixture of ethyl acetate (10 ml) and water (2 ml) was treated with potassium bicarbonate (0.230 g, 2.3 mmol) followed by dibromoformaldoxime (0.354 g, 1.75 mmol) (D. M. Vyas, Y. Chiang and T. W. Doyle, Tetrahedron Letters, 1984, 25, 487–490) and the resulting mixture stirred at 22° C. After 1 h, identical quantities of potassium bicarbonate and dibromoformaldoxime were added and the mixture stirred for another 1.5 h. The reaction mixture was then diluted with ethyl acetate, washed with brine, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. Crystallization of the residue from ether gave 0.300 g (68% yield) of the title material as a white solid. 1HNMR 400 MHz (CDCl3) δ ppm: 1.63 (6H, s, 2×CH3), 4.04 (4H, m, 2×CH2), 4.67 (2H, d, J=6.6 Hz, NCH2), 5.32 (2H, s, OCH2), 6.60 (1H, s, CH), 7.17 (1H, m, aromatic), 7.30–7.36 (4H, m, aromatics), 7.51–7.53 (2H, m, aromatics), 7.60 (1H, dd, J=5.5 Hz and J=8.6 Hz, aromatic), 8.01 (1H, broad t, NH). HRMS (ESI+) calculated for C27H25BrFN4O5 [M+H+]: 583.0992. Found: 583.0986.

後処理

  1. stirringthe mixture stirred for another 1.5 h
  2. washwashed with brine
  3. dry with materialdried over anhydrous magnesium sulfate
  4. concentrationconcentrated under reduced pressure
  5. customCrystallization of the residue from ether

出典と根拠

ORDレコード
ord-379e4c46b3a94f7e8a740084c549ab96
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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