Trifluoroacetic acid → 2-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

HRID 1530586Notes

Reaction equation

HRID 1530586 reaction equation
[CH3:1][C:2]([N:6]1[CH2:11][CH2:10][CH:9]([S:12][C:13]2[CH:14]=[CH:15][C:16]3[O:25][CH2:24][CH2:23][N:22]4[C:18](=[N:19][C:20]([C:26]5[CH:31]=[CH:30][CH:29]=[CH:28][N:27]=5)=[CH:21]4)[C:17]=3[CH:32]=2)[CH2:8][CH2:7]1)([CH3:5])[CH2:3][OH:4].C(O)(C(F)(F)F)=[O:34].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:13]2[CH:14]=[CH:15][C:16]3[O:25][CH2:24][CH2:23][N:22]4[CH:21]=[C:20]([C:26]5[CH:31]=[CH:30][CH:29]=[CH:28][N:27]=5)[N:19]=[C:18]4[C:17]=3[CH:32]=2)=[O:34])[CH2:10][CH2:11]1)([CH3:1])[CH2:3][OH:4]

Participants

5

Reactant 3

HCID 6422Trifluoroacetic acidHCID 70297m-Chloroperbenzoic acidHCID 683130312-Methyl-2-[4-(2-pyridin-2-yl-4,5-dihydro-6-oxa-1,3a-diazabenzo[e]azulen-9-ylsulfanyl)piperidin-1-yl]propan-1-ol

Product 1

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-olYield 52.7%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
0 °C

Procedure

To an ice-cooled solution of 2-methyl-2-[4-(2-pyridin-2-yl-4,5-dihydro-6-oxa-1,3a-diazabenzo[e]azulen-9-ylsulfanyl)piperidin-1-yl]propan-1-ol from Example 3 (187 mg, 0.415 mmol) in DCM (20 mL) was added TFA (160 μL, 2.075 mmol) followed by a solution of m-CPBA (79 mg, 0.456 mmol) in DCM (2 mL). The resulting mixture was stirred for 30 min at 0° C. then volatiles were removed under reduced pressure. The crude material was purified by column chromatography (C18, gradient 10-30% 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. Further purification by column chromatography (Si-PCC, gradient 2-17% 2M NH3/MeOH in DCM) afforded 197 as a light brown foam (102 mg, 52%). LCMS: RT1.87 min [M+H]+ 467.1. 1H NMR (DMSO, 400 MHz): δ 8.71 (1H, d, J=2.27 Hz), 8.53 (1H, ddd, J=4.81, 1.82, 0.94 Hz), 8.00 (1H, dt, J=7.92, 1.08 Hz), 7.95 (1H, s), 7.83 (1H, td, J=7.70, 1.85 Hz), 7.50 (1H, dd, J=8.51, 2.30 Hz), 7.26-7.21 (2H, m), 4.58-4.52 (4H, m), 4.18 (1H, t, J=5.42 Hz), 3.21 (2H, d, J=5.19 Hz), 3.07-2.98 (2H, m), 2.72-2.62 (1H, m), 2.17-2.04 (2H, m), 1.78-1.72 (1H, m), 1.48-1.41 (3H, m), 0.89 (6H, s)

Workup

  1. customwere removed under reduced pressure
  2. customThe crude material was purified by column chromatography (C18, gradient 10-30% MeOH in 0.5% TFA/H2O)
  3. washThe cartridge was washed with MeOH
  4. washthe product was eluted with 0.5M NH3 in MeOH
  5. customFurther purification by column chromatography (Si-PCC, gradient 2-17% 2M NH3/MeOH in DCM)

Sources & evidence

ORD record
ord-2839e2fafe034ca19d74d16b09a7e439
Source dataset
uspto-grants-2015_07
Patent number
US09090628B2

Reaction notes

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