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-ylsulfinyl)piperidin-1-yl)-2-methylpropan-1-ol

HRID 1530601Notes

Reaction equation

HRID 1530601 reaction equation
[F:1][C:2]1[C:24]([S:25][CH:26]2[CH2:31][CH2:30][N:29]([C:32]([CH3:36])([CH3:35])[CH2:33][OH:34])[CH2:28][CH2:27]2)=[CH:23][C:5]2[C:6]3[N:10]([CH2:11][CH2:12][O:13][C:4]=2[CH:3]=1)[CH:9]=[C:8]([C:14]1[N:15]([CH:20]([CH3:22])[CH3:21])[N:16]=[C:17]([CH3:19])[N:18]=1)[N:7]=3.C(O)(C(F)(F)F)=[O:38].C1C=C(Cl)C=C(C(OO)=O)C=1>C(Cl)Cl>[F:1][C:2]1[C:24]([S:25]([CH:26]2[CH2:31][CH2:30][N:29]([C:32]([CH3:36])([CH3:35])[CH2:33][OH:34])[CH2:28][CH2:27]2)=[O:38])=[CH:23][C:5]2[C:6]3[N:10]([CH:9]=[C:8]([C:14]4[N:15]([CH:20]([CH3:22])[CH3:21])[N:16]=[C:17]([CH3:19])[N:18]=4)[N:7]=3)[CH2:11][CH2:12][O:13][C:4]=2[CH:3]=1

Participants

5

Reactant 3

HCID 6422Trifluoroacetic acidHCID 70297m-Chloroperbenzoic acidHCID 683131162-{4-[8-Fluoro-2-(2-isopropyl-5-methyl-2H-[1,2,4]triazol-3-yl)-4,5-dihydro-6-oxa-1,3a-diazabenzo[e]azulen-9-ylsulfanyl]piperidin-1-yl}-2-methylpropan-1-ol

Product 1

HCID 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-olYield 88.6%

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]azulen-9-ylsulfanyl]piperidin-1-yl}-2-methylpropan-1-ol from Example 8 (148 mg, 0.287 mmol) in DCM (10 mL) was added TFA (67 μL, 0.863 mmol) followed by a solution of m-CPBA (55 mg, 0.316 mmol) in DCM (2 mL). The resulting mixture was stirred for 30 min at 0° C. then volatiles were removed under reduced pressure. The crude material was purified by column chromatography (C18, gradient 10-40% MeOH in 0.5% TFA/H2O) affording 212 as a white solid (135 mg, 88%). LCMS: RT 2.58 min [M+H]+ 531.1. 1H NMR (DMSO, 400 MHz): δ 8.69 (1H, d, J=7.99 Hz), 7.91 (1H, s), 7.13 (1H, d, J=10.67 Hz), 5.67-5.56 (1H, m), 4.65-4.50 (4H, m), 4.20 (1H, t, J=5.39 Hz), 3.20 (2H, d, J=5.03 Hz), 3.09-2.97 (2H, m), 2.84-2.73 (1H, m), 2.25 (3H, s), 2.21-2.07 (2H, m), 1.90-1.82 (1H, m), 1.56-1.38 (9H, m), 0.88 (6H, s)

Workup

  1. customwere removed under reduced pressure
  2. customThe crude material was purified by column chromatography (C18, gradient 10-40% MeOH in 0.5% TFA/H2O)

Sources & evidence

ORD record
ord-916251b79f5d42db92ee1dcd5de6d55a
Source dataset
uspto-grants-2015_07
Patent number
US09090628B2

Reaction notes

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