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

HRID 1530524Notes

Reaction equation

HRID 1530524 reaction equation
[C:1]([N:5]1[CH2:10][CH2:9][CH:8]([S:11][C:12]2[CH:13]=[CH:14][C:15]3[O:24][CH2:23][CH2:22][N:21]4[C:17](=[N:18][C:19]([C:25]5[N:26]([CH:30]([CH3:32])[CH3:31])[N:27]=[CH:28][N:29]=5)=[CH:20]4)[C:16]=3[CH:33]=2)[CH2:7][CH2:6]1)([CH3:4])([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>[C:1]([N:5]1[CH2:10][CH2:9][CH:8]([S:11]([C:12]2[CH:13]=[CH:14][C:15]3[O:24][CH2:23][CH2:22][N:21]4[CH:20]=[C:19]([C:25]5[N:26]([CH:30]([CH3:31])[CH3:32])[N:27]=[CH:28][N:29]=5)[N:18]=[C:17]4[C:16]=3[CH:33]=2)=[O:35])[CH2:7][CH2:6]1)([CH3:4])([CH3:2])[CH3:3]

Participants

5

Reactant 3

HCID 6422Trifluoroacetic acidHCID 70297m-Chloroperbenzoic acidHCID 6655859110-(1-tert-butylpiperidin-4-ylthio)-2-(1-isopropyl-1H-1,2,4-triazol-5-yl)-5,6-dihydrobenzo[f]imidazo[1,2-d][1,4]oxazepine2×

Product 1

HCID 6655859210-(1-tert-butylpiperidin-4-ylsulfinyl)-2-(1-isopropyl-1H-1,2,4-triazol-5-yl)-5,6-dihydrobenzo[f]imidazo[1,2-d][1,4]oxazepineYield 78%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a solution of 9-(1-tert-butylpiperidin-4-ylsulfanyl)-2-(2-isopropyl-2H-[1,2,4]triazol-3-yl)-4,5-dihydro-6-oxa-1,3a-diazabenzo[e]azulene, also named as 10-(1-tert-butylpiperidin-4-ylthio)-2-(1-isopropyl-1H-1,2,4-triazol-5-yl)-5,6-dihydrobenzo[f]imidazo[1,2-d][1,4]oxazepine 139 (280 mg, 0.60 mmol) in DCM (30 mL) at 0° C. was added TFA (139 μL, 1.81 mmol) followed by a solution of m-CPBA (114 mg, 0.66 mmol) in DCM (10 mL). The resulting mixture was stirred for 30 min then washed with a saturated aqueous NaHCO3 solution, dried (Na2SO4) and concentrated in vacuo. The resulting residue was purified by column chromatography (Si-PCC, gradient 0-12% 2M NH3/MeOH in DCM then C18, gradient 10-35% MeOH in H2O) affording racemic 140 as a white solid (227 mg, 78%). LCMS: RT 2.55 min [M+H]+ 483.4. 1H NMR (DMSO, 400 MHz): δ 8.77 (1H, d, J=2.30 Hz), 7.94 (1H, s), 7.81 (1H, s), 7.58 (1H, dd, J=8.59, 2.31 Hz), 7.29 (1H, d, J=8.58 Hz), 5.89-5.88 (1H, m), 4.59 (4H, s), 3.18 (2H, s), 2.23 (2H, s), 1.91 (1H, s), 1.87 (2H, s), 1.69-1.64 (2H, m), 1.56 (6H, dd, J=6.63, 3.37 Hz), 1.07 (9H, s)

Workup

  1. washthen washed with a saturated aqueous NaHCO3 solution
  2. dry with materialdried (Na2SO4)
  3. concentrationconcentrated in vacuo
  4. customThe resulting residue was purified by column chromatography (Si-PCC, gradient 0-12% 2M NH3/MeOH in DCM

Sources & evidence

ORD record
ord-4176731d1fde4d98a3f3c41cd1cd2d19
Source dataset
uspto-grants-2015_07
Patent number
US09090628B2

Reaction notes

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