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Sodium methanethiolate → N-(4-Fluoro-2-(3-(methylthio)prop-1-ynyl)benzyl)-3-(benzyloxy)-9,9-dimethyl-4-oxo-4,6,7,9-tetrahydropyrimido[2,1-c][1,4]oxazine-2-carboxamide

HRID 1788209
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HRID 1788209 반응식
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][S-:42].[Na+]>CN(C)C=O.C(OCC)(=O)C>[F:15][C:13]1[CH:12]=[CH:11][C:10]([CH2:16][NH:17][C:18]([C:20]2[N:21]=[C:22]3[N:27]([C:28](=[O:38])[C:29]=2[O:30][CH2:31][C:32]2[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=2)[CH2:26][CH2:25][O:24][C:23]3([CH3:39])[CH3:40])=[O:19])=[C:9]([C:8]#[C:7][CH2:6][S:42][CH3:41])[CH:14]=1
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참가 물질

5

반응물 2

HCID 4378561Sodium methanethiolateHCID 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

생성물 1

HCID 21070013N-(4-Fluoro-2-(3-(methylthio)prop-1-ynyl)benzyl)-3-(benzyloxy)-9,9-dimethyl-4-oxo-4,6,7,9-tetrahydropyrimido[2,1-c][1,4]oxazine-2-carboxamide수율 78.1%

시약·촉매·용매 2

HCID 6228
Dimethylformamide
용매
HCID 8857Ethyl Acetate용매

실험 절차

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 (0.160 g, 0.28 mmol) in N,N-dimethylformamide (3 ml) was treated at 0° C. with sodium thiomethoxide (0.026 g, 0.37 mmol) and the resulting mixture stirred for 2 h. The reaction mixture was then 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 hexane) gave 0.114 g (78% yield) of the title material as a white solid. 1HNMR 400 MHz (CDCl3) δ ppm: 1.64 (6H, s, 2×CH3), 2.28 (3H, s, SCH3), 3.45 (2H, s, SCH2), 4.05 (4H, m, 2×CH2), 4.69 (2H, d, J=6.1 Hz, NCH2), 5.31 (2H, s, OCH2), 6.98 (1H, m, aromatic), 7.15 (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), 7.80 (1H, broad t, NH). HRMS (ESI+) calculated for C28H29FN3O4S [M+H+]: 522.1863; found: 522.1844.

후처리

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

출처 및 근거

ORD 기록
ord-3f6a355a805e457fb1664f39a5be0780
출처 데이터셋
uspto-grants-2009_03
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US07511037B2

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