Lithium aluminum hydride → (2-(1-(2,4-difluorophenyl)-3-methyl-1H-1,2,4-triazol-5-yl)-5,6-dihydrobenzo[f]imidazo[1,2-d][1,4]oxazepin-9-yl)methanamine

HRID 886369Notes

Reaction equation

HRID 886369 reaction equation
[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[N:9]1[C:13]([C:14]2[N:23]=[C:22]3[N:16]([CH2:17][CH2:18][O:19][C:20]4[CH:27]=[C:26]([C:28]#[N:29])[CH:25]=[CH:24][C:21]=43)[CH:15]=2)=[N:12][C:11]([CH3:30])=[N:10]1.[AlH4-].[Li+]>O1CCCC1>[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[N:9]1[C:13]([C:14]2[N:23]=[C:22]3[C:21]4[CH:24]=[CH:25][C:26]([CH2:28][NH2:29])=[CH:27][C:20]=4[O:19][CH2:18][CH2:17][N:16]3[CH:15]=2)=[N:12][C:11]([CH3:30])=[N:10]1

Participants

4

Reactant 2

HCID 28112Lithium aluminum hydrideHCID 582043352-[2-(2,4-difluoro-phenyl)-5-methyl-2H-[1,2,4]triazol-3-yl]-4,5-dihydro-6-oxa-1,3a-diaza-benzo[e]azulene-8-carbonitrile

Product 1

HCID 58204437(2-(1-(2,4-difluorophenyl)-3-methyl-1H-1,2,4-triazol-5-yl)-5,6-dihydrobenzo[f]imidazo[1,2-d][1,4]oxazepin-9-yl)methanamine

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To 2-[2-(2,4-Difluoro-phenyl)-5-methyl-2H-[1,2,4]triazol-3-yl]-4,5-dihydro-6-oxa-1,3a-diaza-benzo[e]azulene-8-carbonitrile in tetrahydrofuran was added Lithium tetrahydroaluminate (1M in THF), dropwise at 0° C. The reaction was stirred for 2 hours and quenched with saturated Na2SO4 until H2 evolution ceased. MgSO4 was added and the whole was diluted with copious amounts of methylene chloride, filtered over celite, and concentrated in vacuo. The crude was purified by flash chromatography (1-15% MeOH in DCM spiked with Et3N) to afford to give 355. MS (ESI+) 409.1. 1H NMR (400 MHz, DMSO) δ 7.89 (s, 1H), 7.68 (td, J=8.7, 6.2 Hz, 1H), 7.64-7.52 (m, 2H), 7.32-7.25 (m, 1H), 6.95 (s, 1H), 6.91 (dd, J=8.2, 1.2 Hz, 1H), 4.48-4.38 (m, 4H), 3.66 (s, 2H), 2.35 (s, 3H).

Workup

  1. customdropwise at 0° C
  2. customquenched with saturated Na2SO4 until H2 evolution
  3. additionMgSO4 was added
  4. additionthe whole was diluted with copious amounts of methylene chloride
  5. filtrationfiltered over celite
  6. concentrationconcentrated in vacuo
  7. customThe crude was purified by flash chromatography (1-15% MeOH in DCM spiked with Et3N)
  8. customto afford

Sources & evidence

ORD record
ord-184b993bb79347ba97541e43bbc81028
Source dataset
uspto-grants-2012_08
Patent number
US08242104B2

Reaction notes

Loading…