Water → HCID 178511688, compound

HRID 2088353Notes

Reaction equation

HRID 2088353 reaction equation
COC1C=C(OC)C=CC=1C[NH:6][C@@H:7]1[CH2:12][CH2:11][C@H:10]([NH:13][S:14]([C:17]2[CH:22]=[CH:21][C:20]([C:23]3[CH:28]=[CH:27][C:26]([F:29])=[CH:25][C:24]=3[F:30])=[CH:19][CH:18]=2)(=[O:16])=[O:15])[CH2:9][CH2:8]1.O>C(#N)C.CCOC(C)=O>[NH2:6][C@@H:7]1[CH2:12][CH2:11][C@H:10]([NH:13][S:14]([C:17]2[CH:18]=[CH:19][C:20]([C:23]3[CH:28]=[CH:27][C:26]([F:29])=[CH:25][C:24]=3[F:30])=[CH:21][CH:22]=2)(=[O:16])=[O:15])[CH2:9][CH2:8]1

Participants

5

Reactant 2

HCID 962WaterHCID 178491123HCID 178491123, compound

Product 1

HCID 178511688HCID 178511688, compoundYield 25%

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
50 °C

Procedure

N-(cis-4-(2,4-Dimethoxybenzylamino)cyclohexyl)-2′,4′-difluorobiphenyl-4-sulfonamide (see ABD787a) (52 mg, 0.10 mmol) was stirred in acetonitrile (3 mL) and water (1 mL) and ceric ammonium nitrate (144 mg, 0.26 mmol) was added. The mixture was stirred at 50° C. overnight and then diluted with EtOAc (15 mL) and washed with water (2×5 mL). The washings were extracted with EtOAc (5 mL) and the combined organics were dried over MgSO4. After evaporation of the solvents, the residue was loaded onto a 1 g SCX column and eluted with MeOH and then 20% 2 M NH3/MeOH in DCM. The resulting material was further purified by chromatography (2 g (solute II cartridge), eluting with 0-10% 2 M NH3/MeOH in DCM to afford the title compound as an off-white powder (9 mg, 25%). 1H NMR (300 MHz, DMSO-d6): δ 0.86-0.98 (2H, m), 1.09-1.26 (2H, m), 1.55-1.68 (4H, m), 2.40 (1H, br s), 2.87 (1H, br s), 4.12 (1H, br s), 7.22 (1H, td, J=8 Hz, 2 Hz), 7.40 (1H, td, J=10 Hz, 2.5 Hz), 7.65 (1H, q, J=7 Hz), 7.71 (2H, d, J=9 Hz) and 7.85 (2H, d, J=9 Hz). LCMS: (MH)+=367.

Workup

  1. washwashed with water (2×5 mL)
  2. extractionThe washings were extracted with EtOAc (5 mL)
  3. dry with materialthe combined organics were dried over MgSO4
  4. customAfter evaporation of the solvents
  5. washeluted with MeOH
  6. customThe resulting material was further purified by chromatography (2 g (solute II cartridge)
  7. washeluting with 0-10% 2 M NH3/MeOH in DCM

Sources & evidence

ORD record
ord-7627cb09f0554354a16f33b18196cb45
Source dataset
uspto-grants-2013_05
Patent number
US08435968B2

Reaction notes

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