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 509011Notes

Reaction equation

HRID 509011 reaction equation
[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]

Participants

6

Reactant 4

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

Product 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-carboxamideYield 26.8%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

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)+.

Workup

  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

Sources & evidence

ORD record
ord-d865c2b26da64e849cd4f0676740f7f9
Source dataset
uspto-grants-2015_08
Patent number
US09096545B2

Reaction notes

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