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

HRID 1530595Notes

Reaction equation

HRID 1530595 reaction equation
[CH:1]([N:4]1[CH2:9][CH2:8][CH:7]([S:10]([C:12]2[CH:13]=[CH:14][C:15]3[O:21][CH2:20][CH2:19][N:18]4[CH:22]=[C:23]([C:25]5[C:30]([CH3:31])=[CH:29][CH:28]=[CH:27][N:26]=5)[N:24]=[C:17]4[C:16]=3[CH:32]=2)=[O:11])[CH2:6][CH2:5]1)([CH3:3])[CH3:2].C(O)(C(F)(F)F)=[O:34].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:12]2[CH:13]=[CH:14][C:15]3[O:21][CH2:20][CH2:19][N:18]4[CH:22]=[C:23]([C:25]5[C:30]([CH3:31])=[CH:29][CH:28]=[CH:27][N:26]=5)[N:24]=[C:17]4[C:16]=3[CH:32]=2)(=[O:34])=[O:11])[CH2:6][CH2:5]1)([CH3:3])[CH3:2]

Participants

5

Reactant 3

HCID 6422Trifluoroacetic acidHCID 70297m-Chloroperbenzoic acidHCID 6655917310-(1-Isopropylpiperidin-4-ylsulfinyl)-2-(3-methylpyridin-2-yl)-5,6-dihydrobenzo[f]imidazo[1,2-d][1,4]oxazepine

Product 1

HCID 6655917410-(1-Isopropylpiperidin-4-ylsulfonyl)-2-(3-methylpyridin-2-yl)-5,6-dihydrobenzo[f]imidazo[1,2-d][1,4]oxazepineYield 68.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To an ice-cooled solution of 9-(1-isopropylpiperidine-4-sulfinyl)-2-(3-methylpyridin-2-yl)-4,5-dihydro-6-oxa-1,3a-diazabenzo[e]azulene 204 (40 mg, 0.088 mmol) in DCM (10 mL) was added TFA (34 μL, 0.44 mmol) followed by a slow addition of a solution of m-CPBA (23 mg, 0.132 mmol) in DCM (2 mL) and the resulting mixture was stirred for 1 h at RT. Volatiles were removed under reduced pressure and the resulting residue 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. Further purification by column chromatography (Si-PCC, gradient 2-8% 2M NH3/MeOH in DCM) afforded 205 as a white solid (28 mg, 68%). LCMS: RT 2.04 min [M+H]+ 467.1. 1H NMR (DMSO, 400 MHz): δ 8.94 (1H, d, J=2.41 Hz), 8.42 (1H, dd, J=4.69, 1.62 Hz), 7.93 (1H, s), 7.70-7.63 (2H, m), 7.29 (1H, d, J=8.61 Hz), 7.20 (1H, dd, J=7.64, 4.66 Hz), 4.67-4.56 (4H, m), 3.21-3.11 (1H, m), 2.86-2.78 (2H, m), 2.72 (3H, s), 2.69-2.60 (1H, m), 2.09 (2H, bt, J=11.50 Hz), 1.89 (2H, bd, J=12.09 Hz), 1.50-1.38 (2H, m), 0.90 (6H, d, J=6.55 Hz)

Workup

  1. customVolatiles were removed under reduced pressure
  2. customthe resulting residue 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
  5. customFurther purification by column chromatography (Si-PCC, gradient 2-8% 2M NH3/MeOH in DCM)

Sources & evidence

ORD record
ord-90ebe97f2a0e4a799753a8ad631185b8
Source dataset
uspto-grants-2015_07
Patent number
US09090628B2

Reaction notes

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