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 1038309ノート

反応式

HRID 1038309 の反応式
[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]

参加物

6

反応物 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

生成物 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 ester収率 34%

試薬・触媒・溶媒 2

HCID 8028Tetrahydrofuran溶媒HCID 8857Ethyl Acetate溶媒

反応条件

温度
50 °C

実験手順

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).

後処理

  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

出典と根拠

ORDレコード
ord-5e17e17f67824a519054f2aac215a50e
出典データセット
uspto-grants-2013_10
特許番号
US08551914B2

反応ノート

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