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

HRID 1530576Notes

Reaction equation

HRID 1530576 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][CH:6]=[N:5]1)([CH3:3])[CH3:2].C(O)(C(F)(F)F)=[O:35].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:35])=[O:23])[CH:20]=[CH:21][C:16]=4[O:15][CH2:14][CH2:13][N:12]3[CH:33]=2)=[N:7][CH:6]=[N:5]1)([CH3:3])[CH3:2]

Participants

5

Reactant 3

HCID 6422Trifluoroacetic acidHCID 70297m-Chloroperbenzoic acidHCID 683128432-(1-isopropyl-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 665588412-(1-isopropyl-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×

Procedure

To a solution of 9-(1-isopropylpiperidine-4-sulfinyl)-2-(2-isopropyl-2H-[1,2,4]triazol-3-yl)-4,5-dihydro-6-oxa-1,3a-diazabenzo[e]azulene 177 (214 mg, 0.456 mmol) and TFA (105 μL, 1.32 mmol) in DCM (10 mL) at 0° C. was added a solution of m-CPBA (95 mg, 0.542 mmol) in DCM (2 mL) and the resulting mixture was stirred for 2 h at RT. Volatiles were removed under reduced pressure and the crude material was purified by column chromatography (C18, gradient 10-45% MeOH in 0.5% TFA/H2O). The product containing fractions were combined and concentrated in vacuo and the resulting residue was loaded onto an Isolute® SCX-2 cartridge which was washed with MeOH and the product eluted with 0.5M NH3 in MeOH affording 178 as a white solid (115 mg, 52%). LCMS: RT 2.68 min [M+H]+ 485.2. 1H NMR (DMSO, 400 MHz): δ 8.89 (1H, d, J=2.40 Hz), 8.01 (1H, s), 7.95 (1H, d, J=0.62 Hz), 7.72 (1H, dd, J=8.63, 2.42 Hz), 7.31 (1H, d, J=8.63 Hz), 5.77-5.66 (1H, m), 4.69-4.58 (4H, m), 3.21-3.11 (1H, m), 2.85-2.77 (2H, m), 2.70-2.60 (1H, m), 2.09 (2H, bt, J=11.51 Hz), 1.92 (2H, bd, J=12.10 Hz), 1.50 (6H, d, J=6.61 Hz), 1.49-1.35 (2H, m), 0.89 (6H, d, J=6.54 Hz)

Workup

  1. customVolatiles were removed under reduced pressure
  2. customthe crude material was purified by column chromatography (C18, gradient 10-45% MeOH in 0.5% TFA/H2O)
  3. additionThe product containing fractions
  4. concentrationconcentrated in vacuo
  5. washwas washed with MeOH
  6. washthe product eluted with 0.5M NH3 in MeOH affording 178 as a white solid (115 mg, 52%)

Sources & evidence

ORD record
ord-956daea409144c2591162b7d6aafbe52
Source dataset
uspto-grants-2015_07
Patent number
US09090628B2

Reaction notes

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