Dimethylformamide → (R)-N-(2,4-Dimethyl-3-(5-oxo-1-(4-(trifluoromethyl)phenyl)-4,5-dihydro-1H-1,2,4-triazol-3-yl)benzyl)tetrahydrofuran-2-carboxamide

HRID 59514

反応式

HRID 59514 の反応式
[NH2:1][CH2:2][C:3]1[C:4]([CH3:26])=[C:5]([C:10]2[NH:11][C:12](=[O:25])[N:13]([C:15]3[CH:20]=[CH:19][C:18]([C:21]([F:24])([F:23])[F:22])=[CH:17][CH:16]=3)[N:14]=2)[C:6]([CH3:9])=[CH:7][CH:8]=1.CN(C=O)C.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.[O:54]1[CH2:58][CH2:57][CH2:56][C@@H:55]1[C:59](O)=[O:60]>C1COCC1>[CH3:26][C:4]1[C:5]([C:10]2[NH:11][C:12](=[O:25])[N:13]([C:15]3[CH:20]=[CH:19][C:18]([C:21]([F:23])([F:24])[F:22])=[CH:17][CH:16]=3)[N:14]=2)=[C:6]([CH3:9])[CH:7]=[CH:8][C:3]=1[CH2:2][NH:1][C:59]([C@H:55]1[CH2:56][CH2:57][CH2:58][O:54]1)=[O:60]

参加物

6

反応物 4

HCID 6228DimethylformamideHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 2734707Tetrahydro-2-furoic acid, (+)-HCID 136492429HCID 136492429、化合物

生成物 1

HCID 136246113(R)-N-(2,4-Dimethyl-3-(5-oxo-1-(4-(trifluoromethyl)phenyl)-4,5-dihydro-1H-1,2,4-triazol-3-yl)benzyl)tetrahydrofuran-2-carboxamide収率 26.8%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

実験手順

To a solution of 5-(3-(aminomethyl)-2,6-dimethylphenyl)-2-(4-(trifluoromethyl)phenyl)-2H-1,2,4-triazol-3(4H)-one (Intermediate-66, 0.050 g, 0.138 mmol) in dry THF:DMF (4 mL:1 mL), TBTU (0.132 g, 0.414 mmol) and TEA (1.0 mL) were added and the reaction mass was stirred for 1 h under nitrogen atmosphere. To the reaction mass, (R)-(−)-tetrahydrofuran-2-carboxylic acid (0.024 g, 0.207 mmol) was added and stirred for 18 h at room temperature. After completion of the reaction, the reaction mass was quenched in water, extracted with ethyl acetate and concentrated to afford crude product which was purified by column chromatography by eluting with solution of 2% ammonia in 10% MeOH:DCM to afford 0.017 g of the title product. 1H NMR (400 MHz, DMSO d6): δ 1.79 (m, 3H), 1.87 (m, 3H), 2.20 (s, 6H), 3.74-3.79 (m, 1H), 3.88-3.92 (m, 1H), 4.25 (d, J=4.5 Hz, 2H), 7.16 (d, J=6.0 Hz, 1H), 7.25 (d, J=6.0 Hz, 1H), 7.82 (d, J=6.6 Hz, 1H), 8.17 (d, J=6.3 Hz, 2H), 8.24 (t, J=4.8 Hz, 2H), 12.30 (br s, 1H); MS (m/z): 461.14 (M+H)+.

後処理

  1. stirringstirred for 18 h at room temperature
  2. customAfter completion of the reaction
  3. customthe reaction mass was quenched in water
  4. extractionextracted with ethyl acetate
  5. concentrationconcentrated
  6. customto afford crude product which
  7. customwas purified by column chromatography
  8. washby eluting with solution of 2% ammonia in 10% MeOH

出典と根拠

ORDレコード
ord-607889fc86474c4aad85952b8b2d9c00
出典データセット
uspto-grants-2016_09
特許番号
US09439890B2

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