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

HRID 1530615Notes

Reaction equation

HRID 1530615 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[CH:30]=[C:29]([CH3:31])[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[CH2:5][CH2:6][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[CH:30]=[C:29]([CH3:31])[CH:28]=[CH:27][N:26]=5)[N:24]=[C:17]4[C:16]=3[CH:32]=2)(=[O:34])=[O:11])[CH2:8][CH2:9]1)([CH3:3])[CH3:2]

Participants

5

Reactant 3

HCID 6422Trifluoroacetic acidHCID 70297m-Chloroperbenzoic acidHCID 6655867810-(1-Isopropylpiperidin-4-ylsulfinyl)-2-(4-methylpyridin-2-yl)-5,6-dihydrobenzo[f]imidazo[1,2-d][1,4]oxazepine

Product 1

HCID 6655867910-(1-Isopropylpiperidin-4-ylsulfonyl)-2-(4-methylpyridin-2-yl)-5,6-dihydrobenzo[f]imidazo[1,2-d][1,4]oxazepineYield 77.8%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
0 °C

Procedure

To an ice-cooled solution of 9-(1-isopropylpiperidine-4-sulfinyl)-2-(4-methylpyridin-2-yl)-4,5-dihydro-6-oxa-1,3a-diazabenzo[e]azulene 223 (86 mg, 0.19 mmol) in DCM (7 mL) was added TFA (74 μL, 0.953 mmol) followed by a slow addition of a solution of m-CPBA (43 mg, 0.248 mmol) in DCM (2 mL) and the resulting mixture was stirred for 3 h at 0° C. 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 column chromatography purification (Si-PCC, gradient 2-8% 2M NH3/MeOH in DCM) afforded 224 as a white solid (69 mg, 77%). LCMS: RT 2.08 min [M+H]+ 467.1. 1H NMR (DMSO, 400 MHz): δ 8.95 (1H, d, J=2.41 Hz), 8.40 (1H, d, J=4.98 Hz), 7.96 (1H, s), 7.80 (1H, s), 7.70 (1H, dd, J=8.62, 2.44 Hz), 7.29 (1H, d, J=8.62 Hz), 7.09 (1H, dd, J=5.05, 1.56 Hz), 4.65-4.55 (4H, m), 3.24-3.15 (1H, m), 2.83 (2H, bd, J=11.14 Hz), 2.70-2.60 (1H, m), 2.41 (3H, s), 2.09 (2H, t, J=11.51 Hz), 1.88 (2H, d, J=12.14 Hz), 1.54-1.41 (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 column chromatography purification (Si-PCC, gradient 2-8% 2M NH3/MeOH in DCM)

Sources & evidence

ORD record
ord-dcfcd55ab8c140fdb07a0e015e51442b
Source dataset
uspto-grants-2015_07
Patent number
US09090628B2

Reaction notes

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