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

반응식

HRID 59514 반응식
[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]

참가 물질

6

반응물 4

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

생성물 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-carboxamide수율 26.8%

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매

실험 절차

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)+.

후처리

  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

출처 및 근거

ORD 기록
ord-607889fc86474c4aad85952b8b2d9c00
출처 데이터셋
uspto-grants-2016_09
특허 번호
US09439890B2

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