Acetic Acid → 2-(1-isopropyl-1H-1,2,4-triazol-5-yl)-10-(4-(pentan-3-yl)piperazin-1-ylsulfonyl)-5,6-dihydrobenzo[f]imidazo[1,2-d][1,4]oxazepine

HRID 1530516Notes

Reaction equation

HRID 1530516 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]=[CH:21][C:20]([S:23]([N:26]5[CH2:31][CH2:30][NH:29][CH2:28][CH2:27]5)(=[O:25])=[O:24])=[CH:19][C:16]=43)[CH:10]=2)=[N:7][CH:6]=[N:5]1)([CH3:3])[CH3:2].[CH3:32][C:33](=O)[CH2:34][CH2:35][CH3:36].CC(O)=O.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCCl>[CH:1]([N:4]1[C:8]([C:9]2[N:18]=[C:17]3[C:16]4[CH:19]=[C:20]([S:23]([N:26]5[CH2:27][CH2:28][N:29]([CH:34]([CH2:35][CH3:36])[CH2:33][CH3:32])[CH2:30][CH2:31]5)(=[O:24])=[O:25])[CH:21]=[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

6

Reactant 4

HCID 176Acetic AcidHCID 78952-Pentanone2×HCID 5049666Sodium triacetoxyborohydride2×HCID 683126992-(2-Isopropyl-2H-[1,2,4]triazol-3-yl)-9-(piperazine-1-sulfonyl)-4,5-dihydro-6-oxa-1,3a-diazabenzo[e]azulene

Product 1

HCID 665585062-(1-isopropyl-1H-1,2,4-triazol-5-yl)-10-(4-(pentan-3-yl)piperazin-1-ylsulfonyl)-5,6-dihydrobenzo[f]imidazo[1,2-d][1,4]oxazepineYield 25%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

A mixture of 2-(2-isopropyl-2H-[1,2,4]triazol-3-yl)-9-(piperazine-1-sulfonyl)-4,5-dihydro-6-oxa-1,3a-diazabenzo[e]azulene (35 mg, 0.08 mmol), pentanone (25 μL, 0.24 mmol), AcOH (9 μL, 0.16 mmol) and 4 Å molecular sieves in DCE (2 mL) was stirred at RT for 1 h before the addition of sodium triacetoxyborohydride (33 mg, 0.16 mmol). The resulting mixture was stirred for 16 h before further pentanone (100 μL, 0.92 mmol) and sodium triacetoxyborohydride (198 mg, 0.96 mmol) were added. The mixture was stirred for 20 h then loaded onto an Isolute® SCX-2 cartridge which was washed with MeOH and the product eluted with 2M NH3/MeOH. The resulting residue was purified by column chromatography (Si-PCC, gradient 0-10% MeOH in DCM) to afford 134 (10 mg, 25%) as a white solid. LCMS: RT 3.13 min [M+H]+ 514.4. 1H NMR (CDCl3, 400 MHz): δ 8.95 (1H, d, J=2.36 Hz), 7.88 (1H, s), 7.70 (1H, s), 7.65 (1H, dd, J=8.59, 2.37 Hz), 7.17 (1H, d, J=8.60 Hz), 5.94-5.85 (1H, m), 4.59-4.58 (2H, m), 4.52-4.51 (2H, m), 3.05 (4H, s), 2.61 (4H, s), 2.13-2.10 (1H, m), 1.60 (6H, d, J=6.64 Hz), 1.46-1.35 (2H, m), 1.29-1.27 (2H, m), 0.83 (6H, t, J=7.36 Hz)

Workup

  1. additionwere added
  2. washwas washed with MeOH
  3. washthe product eluted with 2M NH3/MeOH
  4. customThe resulting residue was purified by column chromatography (Si-PCC, gradient 0-10% MeOH in DCM)

Sources & evidence

ORD record
ord-6b83e29265d14073b8374f564b882413
Source dataset
uspto-grants-2015_07
Patent number
US09090628B2

Reaction notes

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