Trifluoroacetic acid → 2-(4-(2-(1-isopropyl-1H-1,2,4-triazol-5-yl)-5,6-dihydrobenzo[f]imidazo[1,2-d][1,4]oxazepin-10-ylsulfinyl)piperidin-1-yl)-2-methylpropan-1-ol

HRID 1530578Notes

Reaction equation

HRID 1530578 reaction equation
[CH:1]([N:4]1[C:8]([C:9]2[N:18]=[C:17]3[N:11]([CH2:12][CH2:13][O:14][C:15]4[CH:22]=[CH:21][C:20]([S:23][CH:24]5[CH2:29][CH2:28][N:27]([C:30]([CH3:34])([CH3:33])[CH2:31][OH:32])[CH2:26][CH2:25]5)=[CH:19][C:16]=43)[CH:10]=2)=[N:7][CH:6]=[N:5]1)([CH3:3])[CH3:2].C(O)(C(F)(F)F)=[O:36].C1C=C(Cl)C=C(C(OO)=O)C=1>C(Cl)Cl>[CH:1]([N:4]1[C:8]([C:9]2[N:18]=[C:17]3[C:16]4[CH:19]=[C:20]([S:23]([CH:24]5[CH2:25][CH2:26][N:27]([C:30]([CH3:34])([CH3:33])[CH2:31][OH:32])[CH2:28][CH2:29]5)=[O:36])[CH:21]=[CH:22][C:15]=4[O:14][CH2:13][CH2:12][N:11]3[CH:10]=2)=[N:7][CH:6]=[N:5]1)([CH3:3])[CH3:2]

Participants

5

Reactant 3

HCID 6422Trifluoroacetic acidHCID 70297m-Chloroperbenzoic acidHCID 683128922-{4-[2-(2-Isopropyl-2H-[1,2,4]triazol-3-yl)-4,5-dihydro-6-oxa-1,3a-diazabenzo[e]azulen-9-ylsulfanyl]piperidin-1-yl}-2-methylpropan-1-ol

Product 1

HCID 665589162-(4-(2-(1-isopropyl-1H-1,2,4-triazol-5-yl)-5,6-dihydrobenzo[f]imidazo[1,2-d][1,4]oxazepin-10-ylsulfinyl)piperidin-1-yl)-2-methylpropan-1-ol

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
0 °C

Procedure

To an ice-cooled solution of 2-{4-[2-(2-isopropyl-2H-[1,2,4]triazol-3-yl)-4,5-dihydro-6-oxa-1,3a-diazabenzo[e]azulen-9-ylsulfanyl]piperidin-1-yl}-2-methylpropan-1-ol from Example 1 (229 mg, 0.474 mmol) in DCM (10 mL) was added TFA (110 μL, 1.42 mmol) followed by a solution of m-CPBA (82 mg, 0.474 mmol) in DCM (2 mL). The resulting mixture was stirred for 1 h at 0° C. then volatiles were removed under reduced pressure. The crude material was purified by column chromatography (C18, gradient 10-35% MeOH in 0.5% TFA/H2O) and then loaded onto an Isolute® SCX-2 cartridge. The cartridge was washed with MeOH and the product was eluted with 0.5M NH3 in MeOH affording 186 as a white solid (177 mg, 75%). LCMS: RT 2.45 min [M+H]+ 499.2. 1H NMR (DMSO, 400 MHz): δ 8.59 (1H, d, J=2.26 Hz), 7.97 (1H, s), 7.93 (1H, s), 7.53 (1H, dd, J=8.53, 2.28 Hz), 7.25 (1H, d, J=8.53 Hz), 5.80-5.67 (1H, m), 4.61-4.43 (4H, m), 4.22-4.16 (1H, m), 3.21 (2H, d, J=4.59 Hz), 3.06-2.96 (2H, m), 2.73-2.63 (1H, m), 2.17-2.05 (2H, m), 1.77 (1H, bd, J=12.25 Hz), 1.59 (1H, bd, J=12.59 Hz), 1.52-1.34 (8H, m), 0.88 (6H, s)

Workup

  1. customwere removed under reduced pressure
  2. customThe crude material was purified by column chromatography (C18, gradient 10-35% MeOH in 0.5% TFA/H2O)
  3. washThe cartridge was washed with MeOH
  4. washthe product was eluted with 0.5M NH3 in MeOH affording 186 as a white solid (177 mg, 75%)

Sources & evidence

ORD record
ord-d18682e2fd774987bde50acd1365c3cc
Source dataset
uspto-grants-2015_07
Patent number
US09090628B2

Reaction notes

Loading…