Trifluoroacetic acid → 2-(4-(9-fluoro-2-(1-isopropyl-3-methyl-1H-1,2,4-triazol-5-yl)-5,6-dihydrobenzo[f]imidazo[1,2-d][1,4]oxazepin-10-ylsulfinyl)piperidin-1-yl)-2-methylpropanamide

HRID 1530613Notes

Reaction equation

HRID 1530613 reaction equation
[F:1][C:2]1[C:24]([S:25][CH:26]2[CH2:31][CH2:30][N:29]([C:32]([CH3:37])([CH3:36])[C:33]([NH2:35])=[O:34])[CH2:28][CH2:27]2)=[CH:23][C:5]2[C:6]3[N:10]([CH2:11][CH2:12][O:13][C:4]=2[CH:3]=1)[CH:9]=[C:8]([C:14]1[N:15]([CH:20]([CH3:22])[CH3:21])[N:16]=[C:17]([CH3:19])[N:18]=1)[N:7]=3.C(O)(C(F)(F)F)=[O:39].C1C=C(Cl)C=C(C(OO)=O)C=1>C(Cl)Cl>[F:1][C:2]1[C:24]([S:25]([CH:26]2[CH2:31][CH2:30][N:29]([C:32]([CH3:37])([CH3:36])[C:33]([NH2:35])=[O:34])[CH2:28][CH2:27]2)=[O:39])=[CH:23][C:5]2[C:6]3[N:10]([CH:9]=[C:8]([C:14]4[N:15]([CH:20]([CH3:22])[CH3:21])[N:16]=[C:17]([CH3:19])[N:18]=4)[N:7]=3)[CH2:11][CH2:12][O:13][C:4]=2[CH:3]=1

Participants

5

Reactant 3

HCID 6422Trifluoroacetic acidHCID 70297m-Chloroperbenzoic acidHCID 683130762-{4-[8-Fluoro-2-(2-isopropyl-5-methyl-2H-[1,2,4]triazol-3-yl)-4,5-dihydro-6-oxa-1,3a-diazabenzo[e]azulen-9-ylsulfanyl]piperidin-1-yl}isobutyramide

Product 1

HCID 665585992-(4-(9-fluoro-2-(1-isopropyl-3-methyl-1H-1,2,4-triazol-5-yl)-5,6-dihydrobenzo[f]imidazo[1,2-d][1,4]oxazepin-10-ylsulfinyl)piperidin-1-yl)-2-methylpropanamideYield 60%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
0 °C

Procedure

To an ice-cooled solution of 2-{4-[8-fluoro-2-(2-isopropyl-5-methyl-2H-[1,2,4]triazol-3-yl)-4,5-dihydro-6-oxa-1,3a-diazabenzo[e]azulen-9-ylsulfanyl]piperidin-1-yl}isobutyramide from Example 8 (96 mg, 0.183 mmol) in DCM (10 mL) was added TFA (42 μL, 0.548 mmol) followed by a solution of m-CPBA (35 mg, 0.201 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 10-50% 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. The product containing fractions were concentrated in vacuo and further purified by column chromatography (Si-PCC, gradient 2-12% MeOH in DCM) affording 220 as a white solid (59 mg, 60%). LCMS: RT 2.54 min [M+H]+ 544.1. 1H NMR (DMSO, 400 MHz): δ 8.72 (1H, d, J=7.98 Hz), 7.93 (1H, s), 7.17-7.09 (2H, m), 6.86 (1H, s), 5.68-5.56 (1H, m), 4.67-4.50 (4H, m), 2.88-2.74 (3H, m), 2.26 (3H, s), 2.19-2.04 (2H, m), 1.92-1.84 (1H, m), 1.76-1.51 (3H, m), 1.50-1.42 (6H, m), 1.03 (6H, d, J=4.44 Hz)

Workup

  1. customwere removed under reduced pressure
  2. customThe crude material was purified by column chromatography (C18, gradient 10-50% 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. additionThe product containing fractions
  6. concentrationwere concentrated in vacuo
  7. customfurther purified by column chromatography (Si-PCC, gradient 2-12% MeOH in DCM)

Sources & evidence

ORD record
ord-31f736dc5ef34dd4939f2026a5c576f9
Source dataset
uspto-grants-2015_07
Patent number
US09090628B2

Reaction notes

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