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

HRID 1530597Notes

Reaction equation

HRID 1530597 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:22]([CH:24]5[CH2:29][CH2:28][N:27]([CH:30]([CH3:32])[CH3:31])[CH2:26][CH2:25]5)=[O:23])[CH:20]=[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]=[C:19]([S:22]([CH:24]5[CH2:25][CH2:26][N:27]([CH:30]([CH3:32])[CH3:31])[CH2:28][CH2:29]5)(=[O:36])=[O:23])[CH:20]=[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 665585082-(1-isopropyl-3-methyl-1H-1,2,4-triazol-5-yl)-10-(1-isopropylpiperidin-4-ylsulfinyl)-5,6-dihydrobenzo[f]imidazo[1,2-d][1,4]oxazepine

Product 1

HCID 665584202-(1-isopropyl-3-methyl-1H-1,2,4-triazol-5-yl)-10-(1-isopropylpiperidin-4-ylsulfonyl)-5,6-dihydrobenzo[f]imidazo[1,2-d][1,4]oxazepine

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)-4,5-dihydro-6-oxa-1,3a-diazabenzo[e]azulene 206 (35 mg, 0.0731 mmol) in DCM (6 mL) was added TFA (17 μL, 0.306 mmol) followed by a slow addition of a solution of m-CPBA (16 mg, 0.0951 mmol) in DCM (1 mL) and the resulting mixture was stirred for 2 h at 0° C. Volatiles were removed under reduced pressure and the resulting residue was purified by column chromatography (C18, gradient 10-40% 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 affording 208 as a white solid (24 mg, 66%). LCMS: RT 2.68 min [M+H]+ 499.1. 1H NMR (DMSO, 400 MHz): δ 8.87 (1H, d, J=2.40 Hz), 7.97 (1H, s), 7.71 (1H, dd, J=10.93, 2.38 Hz), 7.30 (1H, d, J=8.63 Hz), 5.70-5.58 (1H, m), 4.68-4.56 (4H, m), 3.20-3.10 (1H, m), 2.84-2.77 (2H, m), 2.68-2.59 (1H, m), 2.27 (3H, s), 2.09 (2H, bt, J=11.46 Hz), 1.91 (2H, bd, J=12.10 Hz), 1.54-1.34 (8H, m), 0.89 (6H, d, J=6.55 Hz)

Workup

  1. customVolatiles were removed under reduced pressure
  2. customthe resulting residue was purified by column chromatography (C18, gradient 10-40% MeOH in 0.5% TFA/H2O)
  3. washThe cartridge was washed with MeOH
  4. washthe product eluted with 0.5M NH3 in MeOH affording 208 as a white solid (24 mg, 66%)

Sources & evidence

ORD record
ord-a7b2d4eae3d247e8a5102e43160f8498
Source dataset
uspto-grants-2015_07
Patent number
US09090628B2

Reaction notes

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