Nitromethane → N-(4-Fluoro-2-(3-methylisoxazol-5-yl)benzyl)-3-(benzyloxy)-9,9-dimethyl-4-oxo-4,6,7,9-tetrahydropyrimido[2,1-c][1,4]oxazine-2-carboxamide

HRID 1788204ノート

反応式

HRID 1788204 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].[N+:35]([CH3:38])([O-])=[O:36].[Cl-].[CH3:40]OC1N=C(OC)N=C([N+]2(C)CCOCC2)N=1>CS(C)=O.CN(C)C1C=CN=CC=1.C(OCC)(=O)C>[F:34][C:32]1[CH:31]=[CH:30][C:4]([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])=[C:3]([C:1]2[O:36][N:35]=[C:38]([CH3:40])[CH:2]=2)[CH:33]=1

参加物

7

反応物 3

HCID 6375Nitromethane2 回HCID 27340594-(4,6-Dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride2 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 21070011N-(4-Fluoro-2-(3-methylisoxazol-5-yl)benzyl)-3-(benzyloxy)-9,9-dimethyl-4-oxo-4,6,7,9-tetrahydropyrimido[2,1-c][1,4]oxazine-2-carboxamide収率 73.5%

試薬・触媒・溶媒 3

HCID 142844-(Dimethylamino)pyridine触媒2 回HCID 679Dimethyl Sulfoxide溶媒HCID 8857Ethyl Acetate溶媒

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 (0.150 g, 0.32 mmol) in dimethyl sulfoxide (5 ml) was treated with nitromethane (0.14 ml, 1.92 mmol), 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride (DMTMM) (0.241 g, 1.0 mmol) (M. Kunishima et al., Tetrahedron, 55, 1999, 13159-13170) and 4-(dimethylamino)pyridine (DMAP) (0.010 g) and the resulting mixture stirred at 22° C. for 16 h. Identical quantities of nitromethane, DMTMM and DMAP were then added and the mixture was stirred for another 24 h. The reaction mixture was diluted with ethyl acetate, washed with saturated sodium bicarbonate and brine, then dried over anhydrous magnesium sulfate and concentrated under reduced pressure. Chromatography of the residue on silica gel (elution gradient of ethyl acetate in dichloromethane) gave 0.122 g (73% yield) of the title material as a white solid. 1HNMR 400 MHz (CDCl3) δ ppm: 1.62 (6H, s, 2×CH3), 2.39 (3H, s, CH3), 4.04 (4H, m, 2×CH2), 4.69 (2H, d, J=6.1 Hz, NCH2), 5.31 (2H, s, OCH2), 6.36 (1H, m, CH), 7.13 (1H, m, aromatic), 7.30-7.35 (4H, m, aromatics), 7.50-7.53 (2H, m, aromatics), 7.58 (1H,dd, J=5.5 Hz and J=8.6 Hz, aromatic), 8.06 (1H, broad t, NH). HRMS (ESI+) calculated for C28H28FN4O5 [M+H+]: 519.2044; found: 519.2059.

後処理

  1. stirringthe mixture was stirred for another 24 h
  2. washwashed with saturated sodium bicarbonate and brine
  3. dry with materialdried over anhydrous magnesium sulfate
  4. concentrationconcentrated under reduced pressure

出典と根拠

ORDレコード
ord-d57c12050a3c499fabd4fcc742186133
出典データセット
uspto-grants-2009_03
特許番号
US07511037B2

反応ノート

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