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

HRID 1530634Notes

Reaction equation

HRID 1530634 reaction equation
[CH:1]([N:4]1[C:8]([C:9]2[N:10]=[C:11]3[C:17]4[CH:18]=[CH:19][C:20]([S:22]([CH:24]5[CH2:29][CH2:28][N:27]([CH:30]([CH3:32])[CH3:31])[CH2:26][CH2:25]5)=[O:23])=[CH:21][C:16]=4[O:15][CH2:14][CH2:13][N:12]3[CH:33]=2)=[N:7][C:6]([CH3:34])=[N:5]1)([CH3:3])[CH3:2].C(O)(C(F)(F)F)=[O:36].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]=[CH:19][C:20]([S:22]([CH:24]5[CH2:29][CH2:28][N:27]([CH:30]([CH3:32])[CH3:31])[CH2:26][CH2:25]5)(=[O:36])=[O:23])=[CH:21][C:16]=4[O:15][CH2:14][CH2:13][N:12]3[CH:33]=2)=[N:7][C:6]([CH3:34])=[N:5]1)([CH3:3])[CH3:2]

Participants

5

Reactant 3

HCID 6422Trifluoroacetic acidHCID 70297m-Chloroperbenzoic acidHCID 665590012-(1-isopropyl-3-methyl-1H-1,2,4-triazol-5-yl)-9-(1-isopropylpiperidin-4-ylsulfinyl)-5,6-dihydrobenzo[f]imidazo[1,2-d][1,4]oxazepine

Product 1

HCID 683130002-(1-isopropyl-3-methyl-1H-1,2,4-triazol-5-yl)-9-(1-isopropylpiperidin-4-ylsulfonyl)-5,6-dihydrobenzo[f]imidazo[1,2-d][1,4]oxazepineYield 81%

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)-8-(1-isopropylpiperidine-4-sulfinyl)-4,5-dihydro-6-oxa-1,3a-diazabenzo[e]azulene 242 (38 mg, 0.078 mmol) in DCM (4 mL) was added TFA (30 μL, 0.39 mmol) followed by a solution of m-CPBA (18 mg, 0.101 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 244 as a white solid (31 mg, 81%). LCMS: RT 2.77 min [M+H]+ 499.1. 1H NMR (CD3OD, 400 MHz): δ 8.73 (1H, d, J=8.46 Hz), 7.84 (1H, s), 7.60 (1H, dd, J=8.47, 1.85 Hz), 7.55 (1H, d, J=1.82 Hz), 5.95-5.82 (1H, m), 4.65-4.57 (4H, m), 3.22-3.11 (1H, m), 2.99 (2H, bd, J=11.61 Hz), 2.77-2.64 (1H, m), 2.37 (3H, s), 2.20 (2H, t, J=11.89 Hz), 2.01 (2H, d, J=12.72 Hz), 1.73 (2H, td, J=12.41, 3.93 Hz), 1.55 (6H, d, J=6.65 Hz), 1.03 (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-3902ef4089ea4c90b72fa9a6717db2c2
Source dataset
uspto-grants-2015_07
Patent number
US09090628B2

Reaction notes

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