Trifluoroacetic acid → 2-(1-isopropyl-3-methyl-1H-1,2,4-triazol-5-yl)-10-(1-isopropylpiperidin-4-ylsulfonyl)-9-methyl-5,6-dihydrobenzo[f]imidazo[1,2-d][1,4]oxazepine

HRID 1530633Notes

Reaction equation

HRID 1530633 reaction equation
[CH:1]([N:4]1[C:8]([C:9]2[N:10]=[C:11]3[C:17]4[CH:18]=[C:19]([S:23]([CH:25]5[CH2:30][CH2:29][N:28]([CH:31]([CH3:33])[CH3:32])[CH2:27][CH2:26]5)=[O:24])[C:20]([CH3:22])=[CH:21][C:16]=4[O:15][CH2:14][CH2:13][N:12]3[CH:34]=2)=[N:7][C:6]([CH3:35])=[N:5]1)([CH3:3])[CH3:2].C(O)(C(F)(F)F)=[O:37].C1C=C(Cl)C=C(C(OO)=O)C=1>C(Cl)Cl>[CH:1]([N:4]1[C:8]([C:9]2[N:10]=[C:11]3[C:17]4[CH:18]=[C:19]([S:23]([CH:25]5[CH2:30][CH2:29][N:28]([CH:31]([CH3:33])[CH3:32])[CH2:27][CH2:26]5)(=[O:37])=[O:24])[C:20]([CH3:22])=[CH:21][C:16]=4[O:15][CH2:14][CH2:13][N:12]3[CH:34]=2)=[N:7][C:6]([CH3:35])=[N:5]1)([CH3:2])[CH3:3]

Participants

5

Reactant 3

HCID 6422Trifluoroacetic acidHCID 70297m-Chloroperbenzoic acidHCID 665586802-(1-isopropyl-3-methyl-1H-1,2,4-triazol-5-yl)-10-(1-isopropylpiperidin-4-ylsulfinyl)-9-methyl-5,6-dihydrobenzo[f]imidazo[1,2-d][1,4]oxazepine

Product 1

HCID 683130062-(1-isopropyl-3-methyl-1H-1,2,4-triazol-5-yl)-10-(1-isopropylpiperidin-4-ylsulfonyl)-9-methyl-5,6-dihydrobenzo[f]imidazo[1,2-d][1,4]oxazepineYield 44.8%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
0 °C

Procedure

To an ice-cooled solution of 2-(2-isopropyl-5-methyl-2H-[1,2,4]triazol-3-yl)-9-(1-isopropylpiperidine-4-sulfinyl)-8-methyl-4,5-dihydro-6-oxa-1,3a-diazabenzo[e]azulene 225 (30 mg, 0.061 mmol) in DCM (3 mL) was added TFA (24 μL, 0.306 mmol) followed by a solution of m-CPBA (14 mg, 0.0796 mmol) in DCM (1 mL). The resulting mixture was stirred for 3 h at 0° C. then volatiles were removed under reduced pressure. The crude material was purified by column chromatography (C18, gradient 20-50% MeOH in 0.5% TFA/H2O) and then loaded onto an Isolute® SCX-2 cartridge. The cartridge was washed with MeOH and the product eluted with 0.5M NH3 in MeOH. The basic fractions were combined and concentrated in vacuo and the resulting residue was purified by column chromatography (Si-PCC, gradient 3-15% MeOH in DCM) affording 243 as a white solid (14 mg, 44%). LCMS: RT 2.83 min [M+H]+ 513.1. 1H NMR (CD3OD, 400 MHz): δ 9.08 (1H, s), 7.76 (1H, s), 7.10 (1H, s), 5.93-5.80 (1H, m), 4.63-4.53 (4H, m), 3.21-3.10 (1H, m), 3.00 (2H, bd, J=11.56 Hz), 2.77-2.67 (1H, m), 2.64 (3H, s), 2.37 (3H, s), 2.24 (2H, t, J=12.17 Hz), 1.97 (2H, d, J=12.67 Hz), 1.87-1.74 (2H, m), 1.56 (6H, d, J=6.65 Hz), 1.04 (6H, d, J=6.56 Hz)

Workup

  1. customwere removed under reduced pressure
  2. customThe crude material was purified by column chromatography (C18, gradient 20-50% MeOH in 0.5% TFA/H2O)
  3. washThe cartridge was washed with MeOH
  4. washthe product eluted with 0.5M NH3 in MeOH
  5. concentrationconcentrated in vacuo
  6. customthe resulting residue was purified by column chromatography (Si-PCC, gradient 3-15% MeOH in DCM)

Sources & evidence

ORD record
ord-9d425306e4644963b0fb011bb742514c
Source dataset
uspto-grants-2015_07
Patent number
US09090628B2

Reaction notes

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