Trifluoroacetic acid → HCID 66559087, compound

HRID 1530588Notes

Reaction equation

HRID 1530588 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]=[CH:29][CH:28]=[CH:27][N:26]=5)[N:24]=[C:17]4[C:16]=3[CH:31]=2)=[O:11])[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: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]=[CH:29][CH:28]=[CH:27][N:26]=5)[N:24]=[C:17]4[C:16]=3[CH:31]=2)(=[O:33])=[O:11])[CH2:6][CH2:5]1)([CH3:3])[CH3:2]

Participants

5

Reactant 3

HCID 6422Trifluoroacetic acidHCID 70297m-Chloroperbenzoic acidHCID 66559085HCID 66559085, compound

Product 1

HCID 66559087HCID 66559087, compoundYield 75.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To an ice-cooled solution of 9-(1-isopropylpiperidine-4-sulfinyl)-2-pyridin-2-yl-4,5-dihydro-6-oxa-1,3a-diazabenzo[e]azulene 198 (50 mg, 0.1145 mmol) in DCM (10 mL) was added TFA (44 μL, 0.573 mmol) followed by a slow addition of a solution of m-CPBA (30 mg, 0.172 mmol) in DCM (1 mL). The resulting mixture was stirred for 2 h at RT. Volatiles were removed under reduced pressure and the resulting residue was purified by column chromatography (C18, gradient 5-35% 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 200 as a white solid (39 mg, 75%). LCMS: RT 2.05 min [M+H]+ 453.1. 1H NMR (DMSO, 400 MHz): δ 8.95 (1H, d, J=2.41 Hz), 8.53 (1H, ddd, J=4.81, 1.80, 0.93 Hz), 8.00-7.95 (2H, m), 7.84 (1H, td, J=7.69, 1.84 Hz), 7.69 (1H, dd, J=8.62, 2.43 Hz), 7.30-7.22 (2H, m), 4.65-4.54 (4H, m), 3.23-3.13 (1H, m), 2.82 (2H, bd, J=11.14 Hz), 2.68-2.59 (1H, m), 2.08 (2H, bt, J=11.51 Hz), 1.87 (2H, bd, J=12.10 Hz), 1.51-1.40 (2H, m), 0.89 (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 5-35% 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-505e166c318843d5b4c704cce3fcb996
Source dataset
uspto-grants-2015_07
Patent number
US09090628B2

Reaction notes

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