Acetic Acid → 4-(2-(1-isopropyl-1H-1,2,4-triazol-5-yl)-5,6-dihydrobenzo[f]imidazo[1,2-d][1,4]oxazepin-9-yl)-1-methyl-1,2,5,6-tetrahydropyridine-3-carboxamide

HRID 1498484Notes

Reaction equation

HRID 1498484 reaction equation
[CH:1]([N:4]1[C:8]([C:9]2[N:18]=[C:17]3[N:11]([CH2:12][CH2:13][O:14][C:15]4[CH:22]=[C:21]([C:23]5[CH2:28][CH2:27][NH:26][CH2:25][C:24]=5[C:29]([NH2:31])=[O:30])[CH:20]=[CH:19][C:16]=43)[CH:10]=2)=[N:7][CH:6]=[N:5]1)([CH3:3])[CH3:2].C=O.[C:34](O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C(O)(=O)C.C(=O)([O-])O.[Na+]>C(Cl)Cl.CO>[CH:1]([N:4]1[C:8]([C:9]2[N:18]=[C:17]3[C:16]4[CH:19]=[CH:20][C:21]([C:23]5[CH2:28][CH2:27][N:26]([CH3:34])[CH2:25][C:24]=5[C:29]([NH2:31])=[O:30])=[CH:22][C:15]=4[O:14][CH2:13][CH2:12][N:11]3[CH:10]=2)=[N:7][CH:6]=[N:5]1)([CH3:3])[CH3:2]

Participants

8

Reactant 5

HCID 176Acetic AcidHCID 712FormaldehydeHCID 516892Sodium BicarbonateHCID 5049666Sodium triacetoxyborohydrideHCID 582049604-[2-(2-Isopropyl-2H[1,2,4]triazol-3-yl)-4,5-dihydro-6-oxa-1,3a-diaza-benzo[e]azulen-8-yl]-1,2,5,6-tetrahydro-pyridine-3-carboxylic acid amide

Product 1

HCID 582043564-(2-(1-isopropyl-1H-1,2,4-triazol-5-yl)-5,6-dihydrobenzo[f]imidazo[1,2-d][1,4]oxazepin-9-yl)-1-methyl-1,2,5,6-tetrahydropyridine-3-carboxamideYield 62%

Reagents, catalysts & solvents 2

HCID 887MethanolSolvent2×HCID 6344DichloromethaneSolvent2×

Procedure

To a solution of 4-[2-(2-isopropyl-2H[1,2,4]triazol-3-yl)-4,5-dihydro-6-oxa-1,3a-diaza-benzo[e]azulen-8-yl]-1,2,5,6-tetrahydro-pyridine-3-carboxylic acid amide (0.15 g, 0.35 mmol) in DCM (16 mL) and methanol (8 mL) was added formaldehyde (0.053 mL, 37% aq., 0.7 mmol), sodium triacetoxyborohydride (0.11 g, 0.52 mmol) and acetic acid (24 μL, 0.42 mmol). The reaction mixture was stirred at RT for 16 h. Sodium hydrogen carbonate (aq.) and 10% Methanol in DCM were added to the mixture and the organic fraction separated, dried (Na2SO4), filtered and concentrated in vacuo. The resultant residue was subjected to flash chromatography (SiO2, gradient 0 to 10% methanol in DCM) to give 414 (94 mg, 62%). LCMS: RT=2.31 min, [M+H]+=434. 1H NMR 400 MHz (DMSO-d6) δ: 8.32 (1 H, d, J=8.35 Hz), 7.92 (1 H, s), 7.91 (1 H, d, J=0.62 Hz), 7.11 (1 H, br, s), 7.08 (1 H, dd, J=8.37, 1.83 Hz), 7.02 (1 H, br, s), 6.98 (1 H, d, J=1.79 Hz), 5.94-5.86 (1 H, m), 4.53-4.46 (4 H, m), 3.15 (2 H, s), 2.61 (2 H, s), 2.46 (2 H, s), 2.35 (3 H, s), 1.48 (6 H, d, J=6.60 Hz)

Workup

  1. customthe organic fraction separated
  2. dry with materialdried (Na2SO4)
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-ef289edd3f3a489192f37094208db4c3
Source dataset
uspto-grants-2015_12
Patent number
US09198918B2

Reaction notes

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