Dimethylamine → N-(2-(3-(Dimethylamino)prop-1-ynyl)-4-fluorobenzyl)-3-(benzyloxy)-9,9-dimethyl-4-oxo-4,6,7,9-tetrahydropyrimido[2,1-c][1,4]oxazine-2-carboxamide

HRID 348209ノート

反応式

HRID 348209 の反応式
CS(O[CH2:6][C:7]#[C:8][C:9]1[CH:14]=[C:13]([F:15])[CH:12]=[CH:11][C:10]=1[CH2:16][NH:17][C:18]([C:20]1[N:21]=[C:22]2[N:27]([C:28](=[O:38])[C:29]=1[O:30][CH2:31][C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1)[CH2:26][CH2:25][O:24][C:23]2([CH3:40])[CH3:39])=[O:19])(=O)=O.[CH3:41][NH:42][CH3:43]>C(#N)C.O1CCCC1.C(OCC)(=O)C>[CH3:41][N:42]([CH3:43])[CH2:6][C:7]#[C:8][C:9]1[CH:14]=[C:13]([F:15])[CH:12]=[CH:11][C:10]=1[CH2:16][NH:17][C:18]([C:20]1[N:21]=[C:22]2[N:27]([C:28](=[O:38])[C:29]=1[O:30][CH2:31][C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1)[CH2:26][CH2:25][O:24][C:23]2([CH3:39])[CH3:40])=[O:19]

参加物

6

反応物 2

HCID 674DimethylamineHCID 210698463-[2-((3-(Benzyloxy)-9,9-dimethyl-4-oxo-4,6,7,9-tetrahydropyrimido[2,1-c][1,4]oxazine-2-carboxamido)methyl)-5-fluorophenyl]prop-2-ynyl methanesulfonate

生成物 1

HCID 21069978N-(2-(3-(Dimethylamino)prop-1-ynyl)-4-fluorobenzyl)-3-(benzyloxy)-9,9-dimethyl-4-oxo-4,6,7,9-tetrahydropyrimido[2,1-c][1,4]oxazine-2-carboxamide収率 88%

試薬・触媒・溶媒 3

HCID 6342Acetonitrile溶媒HCID 8028Tetrahydrofuran溶媒HCID 8857Ethyl Acetate溶媒

実験手順

A solution of intermediate 183, 3-[2-((3-(benzyloxy)-9,9-dimethyl-4-oxo-4,6,7,9-tetrahydropyrimido[2,1-c][1,4]oxazine-2-carboxamido)methyl)-5-fluorophenyl]prop-2-ynyl methanesulfonate (0.100 g, 0.18 mmol) in acetonitrile (5 ml) was treated at 22° C. with 0.3 ml (0.6 mmol) of a 2 M solution of dimethylamine in tetrahydrofuran and the resulting mixture was stirred for 30 min. The reaction mixture was then diluted with ethyl acetate, washed with saturated sodium bicarbonate, brine, then dried over anhydrous magnesium sulfate and concentrated under reduced pressure to give 0.080 g (88% yield) of the title material as a white solid. 1HNMR 400 MHz (CDCl3) δ ppm: 1.64 (6H, s, 2×CH3), 2.43 (6H, s, 2×NCH3), 3.58 (2H, broad s, CH2), 4.05 (4H, m, 2×CH2), 4.70 (2H, d, J=6.0 Hz, NCH2), 5.30 (2H, s, OCH2), 7.01 (1H, m, aromatic), 7.18 (1H, dd, J=3 Hz and J=9.1 Hz, aromatic), 7.32–7.38 (4H, m, aromatics), 7.50–7.53 (2H, m, aromatics), 7.79 (1H, broad t, NH). HRMS (ESI+) calculated for C29H32FN4O4 [M+H+]: 519.2408. Found: 519.2407.

後処理

  1. washwashed with saturated sodium bicarbonate, brine
  2. dry with materialdried over anhydrous magnesium sulfate
  3. concentrationconcentrated under reduced pressure

出典と根拠

ORDレコード
ord-7623d0da2cfa4601a6ae23d6d1d7846f
出典データセット
uspto-grants-2007_02
特許番号
US07176196B2

反応ノート

読み込み中…