Dimethylamine, hydrochloride → 1-(5-(5,6-dihydrobenzo[f]imidazo[1,2-d][1,4]oxazepin-2-yl)-1-isopropyl-1H-1,2,4-triazol-3-yl)-N,N-dimethylmethanamine

HRID 1498394Notes

Reaction equation

HRID 1498394 reaction equation
[N:1]1[C:2]([C:15]2[N:19]([CH:20]([CH3:22])[CH3:21])[N:18]=[C:17]([CH:23]=O)[N:16]=2)=[CH:3][N:4]2[C:10]=1[C:9]1[CH:11]=[CH:12][CH:13]=[CH:14][C:8]=1[O:7][CH2:6][CH2:5]2.Cl.[CH3:26][NH:27][CH3:28].C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>C(O)(=O)C.C1COCC1.C(Cl)Cl>[N:1]1[C:2]([C:15]2[N:19]([CH:20]([CH3:21])[CH3:22])[N:18]=[C:17]([CH2:23][N:27]([CH3:28])[CH3:26])[N:16]=2)=[CH:3][N:4]2[C:10]=1[C:9]1[CH:11]=[CH:12][CH:13]=[CH:14][C:8]=1[O:7][CH2:6][CH2:5]2

Participants

7

Reactant 3

HCID 10473Dimethylamine, hydrochlorideHCID 5049666Sodium triacetoxyborohydrideHCID 582047025-(4,5-Dihydro-6-oxa-1,3a-diaza-benzo[e]azulen-2-yl)-1-isopropyl-1H-[1,2,4]triazole-3-carbaldehyde

Product 1

HCID 582046501-(5-(5,6-dihydrobenzo[f]imidazo[1,2-d][1,4]oxazepin-2-yl)-1-isopropyl-1H-1,2,4-triazol-3-yl)-N,N-dimethylmethanamineYield 14.2%

Reagents, catalysts & solvents 3

HCID 176Acetic AcidCatalystHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

A mixture of 5-(4,5-dihydro-6-oxa-1,3a-diaza-benzo[e]azulen-2-yl)-1-isopropyl-1H-[1,2,4]triazole-3-carbaldehyde (85 mg, 0.26 mmol), acetic acid (catalytic, 2 drops), 4 Å molecular sieves and dimethylamine hydrochloride (24 mg, 0.29 mmol) in THF (5 mL) was stirred at RT for 10 min before the addition of sodium triacetoxyborohydride (66 mg, 0.31 mmol). After stirring at RT for a further 18 h the reaction mixture was diluted with DCM, the organic layer washed with saturated aqueous sodium bicarbonate followed by water and then brine, then dried (Na2SO4), filtered and concentrated in vacuo. The resultant residue was subjected to RPHPLC (C18 column, gradient 5 to 98% methanol in water+0.1% HCO2H) to give 318 as a white solid (13 mg, 14%). LCMS: RT=3.18 min, [M+H]+353. 1H NMR 400 MHz (DMSO-d6) δ: 8.45 (1 H, dd, J=8.02, 1.76 Hz), 7.97 (1 H, s), 7.39-7.32 (1 H, m), 7.19-7.19 (1 H, m), 7.09 (1 H, dd, J=8.15, 1.25 Hz), 5.89 (1 H, m), 4.54 (4 H, d, J=2.46 Hz), 3.47 (2 H, s), 2.24 (6 H, s), 1.51 (6 H, d, J=6.59 Hz)

Workup

  1. washthe organic layer washed with saturated aqueous sodium bicarbonate
  2. dry with materialbrine, then dried (Na2SO4)
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-73edbd33ba4f423184e69cd0117a17a8
Source dataset
uspto-grants-2015_12
Patent number
US09198918B2

Reaction notes

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