Trifluoroacetic acid → 10-(1-Isopropylpiperidin-4-ylsulfinyl)-2-(3-methylpyridin-2-yl)-5,6-dihydrobenzo[f]imidazo[1,2-d][1,4]oxazepine

HRID 1530594Notes

Reaction equation

HRID 1530594 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[C:29]([CH3:30])=[CH:28][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[CH2:9][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[CH:19]=[C:18]([C:24]5[C:29]([CH3:30])=[CH:28][CH:27]=[CH:26][N:25]=5)[N:17]=[C:16]4[C:15]=3[CH:31]=2)=[O:33])[CH2:6][CH2:5]1)([CH3:3])[CH3:2]

Participants

5

Reactant 3

HCID 6422Trifluoroacetic acidHCID 70297m-Chloroperbenzoic acidHCID 683131209-(1-Isopropylpiperidin-4-ylsulfanyl)-2-(3-methylpyridin-2-yl)-4,5-dihydro-6-oxa-1,3a-diazabenzo[e]azulene

Product 1

HCID 6655917310-(1-Isopropylpiperidin-4-ylsulfinyl)-2-(3-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-(3-methylpyridin-2-yl)-4,5-dihydro-6-oxa-1,3a-diazabenzo[e]azulene from Example 7 (70 mg, 0.161 mmol) in DCM (10 mL) was added TFA (62 μL, 0.805 mmol) followed by a solution of m-CPBA (31 mg, 0.177 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 was eluted with 0.5M NH3 in MeOH affording 204 as a pale orange foam (65 mg, 90%). LCMS: RT1.92 min [M+H]+ 451.1. 1H NMR (DMSO, 400 MHz): δ 8.66 (1H, d, J=2.27 Hz), 8.40 (1H, dd, J=4.69, 1.63 Hz), 7.89 (1H, s), 7.64 (1H, ddd, J=7.65, 1.72, 0.84 Hz), 7.49 (1H, dd, J=8.50, 2.30 Hz), 7.23 (1H, d, J=8.72 Hz), 7.18 (1H, dd, J=7.96, 4.16 Hz), 4.60-4.53 (4H, m), 2.85-2.77 (2H, m), 2.73-2.59 (5H, m), 2.13-2.02 (2H, m), 1.76 (1H, bd, J=12.29 Hz), 1.58 (1H, bd, J=12.37 Hz), 1.52-1.38 (2H, m), 0.90 (6H, d, J=6.54 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 was eluted with 0.5M NH3 in MeOH affording 204 as a pale orange foam (65 mg, 90%)

Sources & evidence

ORD record
ord-d701f4ff66194e559af95ca3aaafc52a
Source dataset
uspto-grants-2015_07
Patent number
US09090628B2

Reaction notes

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