Diisopropylethylamine → HCID 44554652, compound

HRID 714399Notes

Reaction equation

HRID 714399 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([CH:21]=[CH:22][C:23]=1[F:24])[CH2:5][N:6]1[C:10](=[O:11])[N:9]([C:12]2[CH:13]=[C:14]([CH:18]=[CH:19][N:20]=2)[C:15](O)=[O:16])[CH:8]=[N:7]1.C(N(C(C)C)CC)(C)C.O.[OH:35][N:36]1[C:40]2[CH:41]=[CH:42][CH:43]=C[C:39]=2[N:38]=N1.F[B-](F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2C=CC=CC=2N=N1.CC1ON=C(CN)C=1>O1CCCC1>[F:1][C:2]1[CH:3]=[C:4]([CH:21]=[CH:22][C:23]=1[F:24])[CH2:5][N:6]1[C:10](=[O:11])[N:9]([C:12]2[CH:13]=[C:14]([CH:18]=[CH:19][N:20]=2)[C:15]([NH:38][CH2:39][C:40]2[CH:41]=[C:42]([CH3:43])[O:35][N:36]=2)=[O:16])[CH:8]=[N:7]1

Participants

7

Reactant 5

HCID 81531DiisopropylethylamineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 27763061-(5-Methyl-1,2-oxazol-3-yl)methanamineHCID 27960291-Hydroxybenzotriazole hydrateHCID 67153877HCID 67153877, compound

Product 1

HCID 44554652HCID 44554652, compoundYield 71.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A mixture of 2-(1-(3,4-difluorobenzyl)-5-oxo-1H-1,2,4-triazol-4(5H)-yl)isonicotinic acid (0.22 g, 0.66 mmol), diisopropylethylamine (0.6 mL, 9.57 mmol), 1-hydroxybenzotriazole monohydrate (0.20 g, 1.44 mmol) and O-(1H-benzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium tetrafluoroborate (0.40 g, 1.24 mmol) and (5-methylisoxazol-3-yl)methanamine (0.19 g, 0.99 mmol) in tetrahydrofuran (10 mL) was stirred at ambient temperature for 23 hours and concentrated in vacuo. The residue was suspended in a mixture of saturated sodium bicarbonate solution (10 mL) and ether (2.5 mL) and stirred at ambient temperature overnight. The solid was collected by filtration, washed with saturated sodium bicarbonate solution, water, ether, hexanes and dried in vacuo to afford 2-(1-(3,4-difluorobenzyl)-5-oxo-1H-1,2,4-triazol-4(5H)-yl)-N-((5-methylisoxazol-3-yl)methyl)-isonicotinamide as a colorless solid (0.20 g, 71% yield): mp 160-161° C.; 1H NMR (300 MHz, CDCl3) δ 8.62 (s, 1H), 8.53 (d, J=5.7 Hz, 1H), 8.46 (s, 1H), 7.70 (dd, J=5.1, 1.4 Hz, 1H), 7.25-7.09 (m, 4H), 6.03 (s, 1H), 4.96 (s, 2H), 4.67 (d, J=5.7 Hz, 2H), 2.41 (s, 3H); MS (ES+) m/z 427.0 (M+1).

Workup

  1. concentrationconcentrated in vacuo
  2. additionThe residue was suspended in a mixture of saturated sodium bicarbonate solution (10 mL) and ether (2.5 mL)
  3. stirringstirred at ambient temperature overnight
  4. filtrationThe solid was collected by filtration
  5. washwashed with saturated sodium bicarbonate solution, water, ether, hexanes
  6. customdried in vacuo

Sources & evidence

ORD record
ord-f86058de37ce478aa2a2780f24569f7b
Source dataset
uspto-grants-2015_11
Patent number
US09187426B2

Reaction notes

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