Trifluoroacetic acid → 2-(1-isopropyl-3-methyl-1H-1,2,4-triazol-5-yl)-10-(1-isopropylpiperidin-4-ylsulfinyl)-9-methyl-5,6-dihydrobenzo[f]imidazo[1,2-d][1,4]oxazepine

HRID 1530616Notes

Reaction equation

HRID 1530616 reaction equation
[CH:1]([N:4]1[C:8]([C:9]2[N:18]=[C:17]3[N:11]([CH2:12][CH2:13][O:14][C:15]4[CH:22]=[C:21]([CH3:23])[C:20]([S:24][CH:25]5[CH2:30][CH2:29][N:28]([CH:31]([CH3:33])[CH3:32])[CH2:27][CH2:26]5)=[CH:19][C:16]=43)[CH:10]=2)=[N:7][C:6]([CH3:34])=[N:5]1)([CH3:3])[CH3:2].C(O)(C(F)(F)F)=[O:36].C1C=C(Cl)C=C(C(OO)=O)C=1>C(Cl)Cl>[CH:1]([N:4]1[C:8]([C:9]2[N:18]=[C:17]3[C:16]4[CH:19]=[C:20]([S:24]([CH:25]5[CH2:26][CH2:27][N:28]([CH:31]([CH3:33])[CH3:32])[CH2:29][CH2:30]5)=[O:36])[C:21]([CH3:23])=[CH:22][C:15]=4[O:14][CH2:13][CH2:12][N:11]3[CH:10]=2)=[N:7][C:6]([CH3:34])=[N:5]1)([CH3:2])[CH3:3]

Participants

5

Reactant 3

HCID 6422Trifluoroacetic acidHCID 70297m-Chloroperbenzoic acidHCID 683132282-(2-Isopropyl-5-methyl-2H-[1,2,4]triazol-3-yl)-9-(1-isopropylpiperidin-4-ylsulfanyl)-8-methyl-4,5-dihydro-6-oxa-1,3a-diazabenzo[e]azulene

Product 1

HCID 665586802-(1-isopropyl-3-methyl-1H-1,2,4-triazol-5-yl)-10-(1-isopropylpiperidin-4-ylsulfinyl)-9-methyl-5,6-dihydrobenzo[f]imidazo[1,2-d][1,4]oxazepine

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
0 °C

Procedure

To an ice-cooled solution of 2-(2-isopropyl-5-methyl-2H-[1,2,4]triazol-3-yl)-9-(1-isopropylpiperidin-4-ylsulfanyl)-8-methyl-4,5-dihydro-6-oxa-1,3a-diazabenzo[e]azulene from Example 32 (112 mg, 0.233 mmol) in DCM (10 mL) was added TFA (90 μL, 1.165 mmol) followed by a solution of m-CPBA (44 mg, 0.256 mmol) in DCM (2 mL). The resulting mixture was stirred for 20 min at 0° C. then volatiles were removed under reduced pressure. The crude material 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 affording 225 as a white solid (100 mg, 87%). LCMS: RT 2.60 min [M+H]+ 497.1. 1H NMR (DMSO, 400 MHz): δ 8.72 (1H, s), 7.89 (1H, s), 7.00 (1H, s), 5.72-5.60 (1H, m), 4.62-4-47 (4H, m), 2.80 (2H, t, J=11.82 Hz), 2.72-2.57 (2H, m), 2.33 (3H, s), 2.25 (3H, s), 2.18-2.00 (2H, m), 1.81 (1H, bd, J=12.17 Hz), 1.63-1.38 (9H, m), 0.89 (6H, d, J=6.54 Hz)

Workup

  1. customwere removed under reduced pressure
  2. customThe crude material was purified by column chromatography (C18, gradient 20-50% MeOH in 0.5% TFA/H2O)
  3. washThe cartridge was washed with MeOH
  4. washthe product eluted with 0.5M NH3 in MeOH affording 225 as a white solid (100 mg, 87%)

Sources & evidence

ORD record
ord-75f9d285fa02477aa78b6fb34cc10eb0
Source dataset
uspto-grants-2015_07
Patent number
US09090628B2

Reaction notes

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