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 1726640노트

반응식

HRID 1726640 반응식
[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

참가 물질

7

반응물 3

HCID 6375Nitromethane2회HCID 27340594-(4,6-Dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride2회HCID 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

생성물 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-carboxamide수율 73.5%

시약·촉매·용매 3

HCID 142844-(Dimethylamino)pyridine촉매2회HCID 679Dimethyl Sulfoxide용매HCID 8857Ethyl Acetate용매

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온도
22 °C

실험 절차

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.

후처리

  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

출처 및 근거

ORD 기록
ord-3e10656035334d0ab9204e35247cc3d8
출처 데이터셋
uspto-grants-2009_02
특허 번호
US07491819B1

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