Trifluoroacetic acid → 2-Methyl-2-(4-(2-(pyridin-2-yl)-5,6-dihydrobenzo[f]imidazo[1,2-d][1,4]oxazepin-10-ylsulfonyl)piperidin-1-yl)propan-1-ol

HRID 1530587Notes

Reaction equation

HRID 1530587 reaction equation
[CH3:1][C:2]([N:6]1[CH2:11][CH2:10][CH:9]([S:12]([C:14]2[CH:15]=[CH:16][C:17]3[O:23][CH2:22][CH2:21][N:20]4[CH:24]=[C:25]([C:27]5[CH:32]=[CH:31][CH:30]=[CH:29][N:28]=5)[N:26]=[C:19]4[C:18]=3[CH:33]=2)=[O:13])[CH2:8][CH2:7]1)([CH3:5])[CH2:3][OH:4].C(O)(C(F)(F)F)=[O:35].C1C=C(Cl)C=C(C(OO)=O)C=1>C(Cl)Cl>[CH3:5][C:2]([N:6]1[CH2:7][CH2:8][CH:9]([S:12]([C:14]2[CH:15]=[CH:16][C:17]3[O:23][CH2:22][CH2:21][N:20]4[CH:24]=[C:25]([C:27]5[CH:32]=[CH:31][CH:30]=[CH:29][N:28]=5)[N:26]=[C:19]4[C:18]=3[CH:33]=2)(=[O:35])=[O:13])[CH2:10][CH2:11]1)([CH3:1])[CH2:3][OH:4]

Participants

5

Reactant 3

HCID 6422Trifluoroacetic acid2×HCID 70297m-Chloroperbenzoic acid2×HCID 665590842-Methyl-2-(4-(2-(pyridin-2-yl)-5,6-dihydrobenzo[f]imidazo[1,2-d][1,4]oxazepin-10-ylsulfinyl)piperidin-1-yl)propan-1-ol

Product 1

HCID 665590862-Methyl-2-(4-(2-(pyridin-2-yl)-5,6-dihydrobenzo[f]imidazo[1,2-d][1,4]oxazepin-10-ylsulfonyl)piperidin-1-yl)propan-1-olYield 47%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent3×

Procedure

To an ice-cooled solution of 2-methyl-2-[4-(2-pyridin-2-yl-4,5-dihydro-6-oxa-1,3a-diazabenzo[e]azulene-9-sulfinyl)piperidin-1-yl]propan-1-ol 197 (30 mg, 0.064 mmol) in DCM (2 mL) was added TFA (25 μL, 0.318 mmol) followed by a slow addition of a solution of m-CPBA (13 mg, 0.076 mmol) in DCM (0.5 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 5-30% MeOH in 0.5% TFA/H2O). To an ice-cooled solution in DCM (10 mL) of the product thus obtained was added TFA (12 μA) followed by a solution of m-CPBA (13 mg, 0.076 mmol) in DCM (0.5 mL). The mixture was stirred at RT for 1.5 h and then volatiles were removed under reduced pressure. The resulting residue was purified by column chromatography (C18, gradient 5-30% MeOH in 0.5% TFA/H2O) and then loaded onto an Isolute® SCX-2 cartridge which 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 199 as a white solid (14 mg, 47%). LCMS: RT 2.03 min [M+H]+ 483.1. 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), 8.00-7.94 (2H, m), 7.85 (1H, td, J=7.69, 1.84 Hz), 7.68 (1H, dd, J=8.62, 2.43 Hz), 7.29-7.22 (2H, m), 4.65-4.55 (4H, m), 4.21 (1H, t, J=5.42 Hz), 3.22-3.10 (3H, m), 3.07-2.99 (2H, m), 2.09 (2H, bt, J=11.55 Hz), 1.86 (2H, bd, J=12.02 Hz), 1.50-1.37 (2H, m), 0.87 (6H, s)

Workup

  1. customVolatiles were removed under reduced pressure
  2. customthe resulting residue was purified by column chromatography (C18, gradient 5-30% MeOH in 0.5% TFA/H2O)
  3. temperatureTo an ice-cooled solution in DCM (10 mL) of the product
  4. customthus obtained
  5. stirringThe mixture was stirred at RT for 1.5 h
  6. customvolatiles were removed under reduced pressure
  7. customThe resulting residue was purified by column chromatography (C18, gradient 5-30% MeOH in 0.5% TFA/H2O)
  8. washwas washed with MeOH
  9. washthe product eluted with 0.5M NH3 in MeOH
  10. customFurther purification by column chromatography (Si-PCC, gradient 2-8% 2M NH3/MeOH in DCM)

Sources & evidence

ORD record
ord-5aec781b5ccf4e80b41324ab22596c5a
Source dataset
uspto-grants-2015_07
Patent number
US09090628B2

Reaction notes

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