Phosphate → HCID 178462428, 화합물

HRID 1766896노트

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HRID 1766896 반응식
[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C@@:9]([OH:38])([CH2:32][N:33]1[CH:37]=[N:36][CH:35]=[N:34]1)[C@H:10]([S:12][C@@H:13]1[CH2:18][O:17][C@@H:16](/[CH:19]=[CH:20]/[CH:21]=[CH:22]/[C:23]2[CH:30]=[CH:29][C:26]([C:27]#[N:28])=[CH:25][C:24]=2[F:31])[O:15][CH2:14]1)[CH3:11].[C:39](N1C=CN=C1)([N:41]1[CH:45]=[CH:44][N:43]=[CH:42]1)=[O:40].P([O-])([O-])([O-])=O>ClCCl.[H-].[Na+]>[N:41]1([C:39]([O:38][C@:9]([C:3]2[CH:4]=[CH:5][C:6]([F:8])=[CH:7][C:2]=2[F:1])([CH2:32][N:33]2[CH:37]=[N:36][CH:35]=[N:34]2)[C@H:10]([S:12][C@@H:13]2[CH2:18][O:17][C@@H:16](/[CH:19]=[CH:20]/[CH:21]=[CH:22]/[C:23]3[CH:30]=[CH:29][C:26]([C:27]#[N:28])=[CH:25][C:24]=3[F:31])[O:15][CH2:14]2)[CH3:11])=[O:40])[CH:45]=[CH:44][N:43]=[CH:42]1

참가 물질

6

반응물 3

HCID 1061PhosphateHCID 682631,1'-CarbonyldiimidazoleHCID 178462432HCID 178462432, 화합물

생성물 1

HCID 178462428HCID 178462428, 화합물수율 70%

시약·촉매·용매 2

HCID 24758Sodium hydride촉매HCID 6344Dichloromethane용매

실험 절차

4-[(1E,3E)-4-[trans-5-[[(1R,2R)-2-(2,4-Difluorophenyl)-2-hydroxy-1-methyl-3-(1H-1,2,4-triazol-1-yl)propyl]thio]-1,3-dioxan-2-yl]-1,3-butadienyl]-3-fluorobenzonitrile (4.90 g, 9.03 mmol) described in Reference example 1 and 1,1′-carbonyldiimidazole (1.53 g, 9.44 mmol) were dissolved in dichloromethane (20 ml). To the mixture was added sodium hydride (55% dispersion in mineral oil; 10 mg, 2.3×10−4 mol), and the reaction mixture was heated under reflux for 3 hours with stirring. After cooling, a phosphate buffer solution (pH 7.4) was added thereto, and the product was extracted with ethyl acetate. The organic layer was washed with an aqueous solution of sodium chloride, dried over anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure. The residue was subjected to chromatography on a silica gel (120 g) column (eluent; ethyl acetate:hexane=1:1˜1:0) to afford the title compound (4.00 g, 70% yield) as a colorless amorphous solid.

후처리

  1. temperaturethe reaction mixture was heated
  2. temperatureunder reflux for 3 hours
  3. temperatureAfter cooling
  4. extractionthe product was extracted with ethyl acetate
  5. washThe organic layer was washed with an aqueous solution of sodium chloride
  6. dry with materialdried over anhydrous magnesium sulfate
  7. distillationthe solvent was distilled off under reduced pressure

출처 및 근거

ORD 기록
ord-1d00c442ba914392ba35835e03768ae2
출처 데이터셋
uspto-grants-2007_06
특허 번호
US07230023B2

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