Sodium hydride → N-{4-[1-(4-trifluoromethoxyphenyl)-1H-[1,2,4]triazol-3-yl]-benzyl}-N-((2S,3R,4R,5S,6S)-3,4,5-trimethoxy-6-methyl-tetrahydropyran-2-yloxy)-malonamic acid methyl ester

HRID 1038309노트

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HRID 1038309 반응식
[CH3:1][O:2][C:3](=[O:22])[CH2:4][C:5]([NH:7][O:8][C@H:9]1[C@H:14]([O:15][CH3:16])[C@H:13]([O:17][CH3:18])[C@@H:12]([O:19][CH3:20])[C@H:11]([CH3:21])[O:10]1)=[O:6].[H-].[Na+].Br[CH2:26][C:27]1[CH:32]=[CH:31][C:30]([C:33]2[N:37]=[CH:36][N:35]([C:38]3[CH:43]=[CH:42][C:41]([O:44][C:45]([F:48])([F:47])[F:46])=[CH:40][CH:39]=3)[N:34]=2)=[CH:29][CH:28]=1>C1COCC1.CCOC(C)=O>[CH3:1][O:2][C:3](=[O:22])[CH2:4][C:5]([N:7]([CH2:26][C:27]1[CH:32]=[CH:31][C:30]([C:33]2[N:37]=[CH:36][N:35]([C:38]3[CH:43]=[CH:42][C:41]([O:44][C:45]([F:47])([F:46])[F:48])=[CH:40][CH:39]=3)[N:34]=2)=[CH:29][CH:28]=1)[O:8][C@H:9]1[C@H:14]([O:15][CH3:16])[C@H:13]([O:17][CH3:18])[C@@H:12]([O:19][CH3:20])[C@H:11]([CH3:21])[O:10]1)=[O:6]

참가 물질

6

반응물 3

HCID 24758Sodium hydrideHCID 667770563-(4-bromomethylphenyl)-1-(4-trifluoromethoxyphenyl)-1H-[1,2,4]triazoleHCID 86662685N-((2S,3R,4R,5S,6S)-3,4,5-trimethoxy-6-methyl-tetrahydropyran-2-yloxy)-malonamic acid methyl ester

생성물 1

HCID 56848039N-{4-[1-(4-trifluoromethoxyphenyl)-1H-[1,2,4]triazol-3-yl]-benzyl}-N-((2S,3R,4R,5S,6S)-3,4,5-trimethoxy-6-methyl-tetrahydropyran-2-yloxy)-malonamic acid methyl ester수율 34%

시약·촉매·용매 2

HCID 8028Tetrahydrofuran용매HCID 8857Ethyl Acetate용매

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온도
50 °C

실험 절차

To a solution of N-((2S,3R,4R,5S,6S)-3,4,5-trimethoxy-6-methyl-tetrahydropyran-2-yloxy)-malonamic acid methyl ester (P-5; 108 mg, 0.34 mmol) in dry THF (3 mL) was added 60% NaH (14.4 mg, 0.36 mmol) giving gas evolution. To this mixture was added 3-(4-bromomethylphenyl)-1-(4-trifluoromethoxyphenyl)-1H-[1,2,4]triazole (P-7; 106 mg, 0.26 mmol), and the resulting mixture was heated to 50° C. for 21 h. The mixture was then allowed to cool to room temperature and diluted with EtOAc and washed with H2O. The aqueous fraction was extracted with EtOAc. The organic fractions were combined, washed with brine, dried with anhydrous Na2SO4 and evaporated at room temperature under vacuum. The resulting crude material was purified by silica gel chromatography (eluting with 100% Hexane going to 50% EtOAc in Hexane over 15 min and then going to 100% EtOAc over an additional 20 min). The title product (56 mg, 34%) was isolated as a colorless glass: 1H NMR (300 MHz, CDCl3) δ 8.58 (s, 1H), 8.17 (d, J=8.4 Hz, 2H), 7.90-7.70 (m, 2H), 7.41 (dd, J=9.9, 8.4 Hz, 4H), 5.42-5.09 (m, 2H), 4.76 (d, J=15.9 Hz, 1H), 3.83-3.05 (m, 18H), 1,41-1.20 (m, 3H); 13C NMR (151 MHz, CDCl3) δ 167.80, 148.87, 141.93, 137.72, 135.95, 130.20, 128.71, 127.19, 122.81, 121.66, 119.95, 105.05, 82.11, 81.97, 79.79, 76.81, 70.28, 70.04, 60.48, 59.63, 59.20, 58.37, 52.76, 41.66, 30.10, 18.58; ESIMS m/z 639 (M+H).

후처리

  1. customgiving gas evolution
  2. temperatureto cool to room temperature
  3. washwashed with H2O
  4. extractionThe aqueous fraction was extracted with EtOAc
  5. washwashed with brine
  6. dry with materialdried with anhydrous Na2SO4
  7. customevaporated at room temperature under vacuum
  8. customThe resulting crude material was purified by silica gel chromatography (
  9. washeluting with 100% Hexane going to 50% EtOAc in Hexane over 15 min

출처 및 근거

ORD 기록
ord-5e17e17f67824a519054f2aac215a50e
출처 데이터셋
uspto-grants-2013_10
특허 번호
US08551914B2

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