Trifluoroacetic acid → 10-(1-Isopropylpiperidin-4-ylsulfinyl)-2-(4-methylpyridin-2-yl)-5,6-dihydrobenzo[f]imidazo[1,2-d][1,4]oxazepine

HRID 1530614Notes

Reaction equation

HRID 1530614 reaction equation
[CH:1]([N:4]1[CH2:9][CH2:8][CH:7]([S:10][C:11]2[CH:12]=[CH:13][C:14]3[O:23][CH2:22][CH2:21][N:20]4[C:16](=[N:17][C:18]([C:24]5[CH:29]=[C:28]([CH3:30])[CH:27]=[CH:26][N:25]=5)=[CH:19]4)[C:15]=3[CH:31]=2)[CH2:6][CH2:5]1)([CH3:3])[CH3:2].C(O)(C(F)(F)F)=[O:33].C1C=C(Cl)C=C(C(OO)=O)C=1>C(Cl)Cl>[CH:1]([N:4]1[CH2:5][CH2:6][CH:7]([S:10]([C:11]2[CH:12]=[CH:13][C:14]3[O:23][CH2:22][CH2:21][N:20]4[CH:19]=[C:18]([C:24]5[CH:29]=[C:28]([CH3:30])[CH:27]=[CH:26][N:25]=5)[N:17]=[C:16]4[C:15]=3[CH:31]=2)=[O:33])[CH2:8][CH2:9]1)([CH3:3])[CH3:2]

Participants

5

Reactant 3

HCID 6422Trifluoroacetic acidHCID 70297m-Chloroperbenzoic acidHCID 683130359-(1-Isopropylpiperidin-4-ylsulfanyl)-2-(4-methylpyridin-2-yl)-4,5-dihydro-6-oxa-1,3a-diazabenzo[e]azulene

Product 1

HCID 6655867810-(1-Isopropylpiperidin-4-ylsulfinyl)-2-(4-methylpyridin-2-yl)-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 9-(1-isopropylpiperidin-4-ylsulfanyl)-2-(4-methylpyridin-2-yl)-4,5-dihydro-6-oxa-1,3a-diazabenzo[e]azulene from Example 12 (138 mg, 0.317 mmol) in DCM (20 mL) was added TFA (122 μL, 1.59 mmol) followed by a solution of m-CPBA (60 mg, 0.349 mmol) in DCM (2 mL). The resulting mixture was stirred for 15 min at 0° C. then volatiles were removed under reduced pressure. The crude material was purified by column chromatography (C18, gradient 5-40% 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 223 as a colorless foam (114 mg, 80%). LCMS: RT1.94 min [M+H]+ 501.0. 1H NMR (DMSO, 400 MHz): δ 8.70 (1H, d, J=2.27 Hz), 8.38 (1H, d, J=4.97 Hz), 7.92 (1H, s), 7.81 (1H, s), 7.50 (1H, dd, J=8.51, 2.30 Hz), 7.23 (1H, d, J=8.51 Hz), 7.07 (1H, d, J=5.03 Hz), 4.59-4.50 (4H, m), 2.86-2.78 (2H, m), 2.74-2.58 (2H, m), 2.39 (3H, s), 2.15-2.01 (2H, m), 1.76 (1H, bd, J=12.05 Hz), 1.59-1.43 (3H, m), 0.90 (6H, d, J=6.53 Hz)

Workup

  1. customwere removed under reduced pressure
  2. customThe crude material was purified by column chromatography (C18, gradient 5-40% MeOH in 0.5% TFA/H2O)
  3. washThe cartridge was washed with MeOH
  4. washthe product eluted with 0.5M NH3 in MeOH affording 223 as a colorless foam (114 mg, 80%)

Sources & evidence

ORD record
ord-0249acfb702a4de1834294f770a4d997
Source dataset
uspto-grants-2015_07
Patent number
US09090628B2

Reaction notes

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