Trifluoroacetic acid → 9-fluoro-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 1530600Notes

Reaction equation

HRID 1530600 reaction equation
[F:1][C:2]1[C:24]([S:25]([CH:27]2[CH2:32][CH2:31][N:30]([CH:33]([CH3:35])[CH3:34])[CH2:29][CH2:28]2)=[O:26])=[CH:23][C:5]2[C:6]3[N:7]([CH:11]=[C:12]([C:14]4[N:18]([CH:19]([CH3:21])[CH3:20])[N:17]=[C:16]([CH3:22])[N:15]=4)[N:13]=3)[CH2:8][CH2:9][O:10][C:4]=2[CH:3]=1.C(O)(C(F)(F)F)=[O:37].C1C=C(Cl)C=C(C(OO)=O)C=1>C(Cl)Cl>[F:1][C:2]1[C:24]([S:25]([CH:27]2[CH2:28][CH2:29][N:30]([CH:33]([CH3:35])[CH3:34])[CH2:31][CH2:32]2)(=[O:37])=[O:26])=[CH:23][C:5]2[C:6]3[N:7]([CH:11]=[C:12]([C:14]4[N:18]([CH:19]([CH3:20])[CH3:21])[N:17]=[C:16]([CH3:22])[N:15]=4)[N:13]=3)[CH2:8][CH2:9][O:10][C:4]=2[CH:3]=1

Participants

5

Reactant 3

HCID 6422Trifluoroacetic acidHCID 70297m-Chloroperbenzoic acid2×HCID 665584229-fluoro-2-(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 665584239-fluoro-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]oxazepineYield 41.7%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent3×

Conditions

Temperature
0 °C

Procedure

To an ice-cooled solution of 8-fluoro-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 210 (51 mg, 0.102 mmol) in DCM (8 mL) was added TFA (24 μL, 0.306 mmol) followed by a slow addition of a solution of m-CPBA (21 mg, 0.122 mmol) in DCM (1 mL) and the resulting mixture was stirred for 2.5 h at 0° C. Additional m-CPBA (9 mg) in DCM (0.5 mL) was added and the mixture was stirred for 1 h at RT. Volatiles were then removed under reduced pressure and the resulting residue 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. Further purification by column chromatography (Si-PCC, gradient 5-10% MeOH in DCM) afforded 211 as a white solid (22 mg, 41%). LCMS: RT 2.76 min [M+H]+ 517.1. 1H NMR (DMSO, 400 MHz): δ 8.88 (1H, d, J=8.22 Hz), 7.94 (1H, s), 7.25 (1H, d, J=11.17 Hz), 5.67-5.55 (1H, m), 4.73-4.54 (4H, m), 3.28-3.15 (1H, m), 2.89-2.79 (2H, m), 2.72-2.60 (1H, m), 2.26 (3H, s), 2.13 (2H, bt, J=11.43 Hz), 1.89 (2H, bd, J=12.04 Hz), 1.58-1.41 (8H, m), 0.91 (6H, d, J=6.55 Hz)

Workup

  1. stirringthe mixture was stirred for 1 h at RT
  2. customVolatiles were then removed under reduced pressure
  3. customthe resulting residue was purified by column chromatography (C18, gradient 20-50% MeOH in 0.5% TFA/H2O)
  4. washThe cartridge was washed with MeOH
  5. washthe product eluted with 0.5M NH3 in MeOH
  6. customFurther purification by column chromatography (Si-PCC, gradient 5-10% MeOH in DCM)

Sources & evidence

ORD record
ord-55860d9fa33f4bd8b56bd4e43c63e02c
Source dataset
uspto-grants-2015_07
Patent number
US09090628B2

Reaction notes

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