Trifluoroacetic acid → 2-(4-(9-fluoro-2-(1-isopropyl-3-methyl-1H-1,2,4-triazol-5-yl)-5,6-dihydrobenzo[f]imidazo[1,2-d][1,4]oxazepin-10-ylsulfonyl)piperidin-1-yl)-2-methylpropan-1-ol

HRID 1530612Notes

Reaction equation

HRID 1530612 reaction equation
[F:1][C:2]1[C:24]([S:25]([CH:27]2[CH2:32][CH2:31][N:30]([C:33]([CH3:37])([CH3:36])[CH2:34][OH:35])[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:39].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[CH2:32][CH2:31][N:30]([C:33]([CH3:37])([CH3:36])[CH2:34][OH:35])[CH2:29][CH2:28]2)(=[O:39])=[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 acidHCID 665585092-(4-(9-fluoro-2-(1-isopropyl-3-methyl-1H-1,2,4-triazol-5-yl)-5,6-dihydrobenzo[f]imidazo[1,2-d][1,4]oxazepin-10-ylsulfinyl)piperidin-1-yl)-2-methylpropan-1-ol

Product 1

HCID 665585982-(4-(9-fluoro-2-(1-isopropyl-3-methyl-1H-1,2,4-triazol-5-yl)-5,6-dihydrobenzo[f]imidazo[1,2-d][1,4]oxazepin-10-ylsulfonyl)piperidin-1-yl)-2-methylpropan-1-olYield 38.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
0 °C

Procedure

To an ice-cooled solution of 2-{4-[8-fluoro-2-(2-isopropyl-5-methyl-2H-[1,2,4]triazol-3-yl)-4,5-dihydro-6-oxa-1,3a-diazabenzo[e]azulene-9-sulfinyl]piperidin-1-yl}-2-methylpropan-1-ol 212 (41 mg, 0.0767 mmol) in DCM (8 mL) was added TFA (30 μL, 0.383 mmol) followed by a slow addition of a solution of m-CPBA (17 mg, 0.10 mmol) in DCM (1.5 mL) and the resulting mixture was stirred for 3 h at 0° C. Volatiles were removed under reduced pressure and the resulting residue was purified by column chromatography (C18, gradient 10-45% 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 3-15% MeOH in DCM) afforded 219 as a white solid (16 mg, 38%). LCMS: RT 2.72 min [M+H]+ 547.1. 1H NMR (DMSO, 400 MHz): δ 8.87 (1H, d, J=8.22 Hz), 7.93 (1H, s), 7.24 (1H, d, J=11.15 Hz), 5.66-5.55 (1H, m), 4.70-4.52 (4H, m), 4.21 (1H, t, J=5.47 Hz), 3.24-3.14 (3H, m), 3.08-2.99 (2H, m), 2.25 (3H, s), 2.12 (2H, bt, J=11.72 Hz), 1.86 (2H, bd, J=11.95 Hz), 1.55-1.43 (8H, d, J=6.62 Hz), 0.88 (6H, s)

Workup

  1. customVolatiles were removed under reduced pressure
  2. customthe resulting residue was purified by column chromatography (C18, gradient 10-45% MeOH in 0.5% TFA/H2O)
  3. washThe cartridge was washed with MeOH
  4. washthe product eluted with 0.5M NH3 in MeOH
  5. customFurther purification by column chromatography (Si-PCC, gradient 3-15% MeOH in DCM)

Sources & evidence

ORD record
ord-cbdab754550e4e5c9347fe9a63516845
Source dataset
uspto-grants-2015_07
Patent number
US09090628B2

Reaction notes

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