Toluene → HCID 86710170, compound

HRID 705394Notes

Reaction equation

HRID 705394 reaction equation
[CH:1]1([C:4]2[C:5]([N:25]([CH2:30][CH2:31][CH2:32][C:33]([NH:35][NH2:36])=[O:34])[S:26]([CH3:29])(=[O:28])=[O:27])=[CH:6][C:7]3[O:11][C:10]([C:12]4[CH:17]=[CH:16][C:15]([F:18])=[CH:14][CH:13]=4)=[C:9]([C:19]4[NH:20][CH:21]=[CH:22][N:23]=4)[C:8]=3[CH:24]=2)[CH2:3][CH2:2]1.[C:37](Cl)(Cl)=[O:38].C1(C)C=CC=CC=1>C(Cl)(Cl)Cl.O1CCCC1>[CH:1]1([C:4]2[C:5]([N:25]([CH2:30][CH2:31][CH2:32][C:33]3[O:34][C:37](=[O:38])[NH:36][N:35]=3)[S:26]([CH3:29])(=[O:28])=[O:27])=[CH:6][C:7]3[O:11][C:10]([C:12]4[CH:17]=[CH:16][C:15]([F:18])=[CH:14][CH:13]=4)=[C:9]([C:19]4[NH:20][CH:21]=[CH:22][N:23]=4)[C:8]=3[CH:24]=2)[CH2:3][CH2:2]1

Participants

6

Reactant 3

HCID 1140TolueneHCID 6371PhosgeneHCID 86710171HCID 86710171, compound

Product 1

HCID 86710170HCID 86710170, compoundYield 71%

Reagents, catalysts & solvents 2

HCID 6212ChloroformSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
85 °C

Procedure

To a solution of N-(5-cyclopropyl-2-(4-fluorophenyl)-3-(1H-imidazol-2-yl)benzofuran-6-yl)-N-(4-hydrazinyl-4-oxobutyl)methanesulfonamide (13 mg, 0.025 mmol) in anhydrous CHCl3 (400 μL) and anhydrous tetrahydrofuran (400 μL) was added 20 wt % phosgene in toluene (66.9 μL, 0.127 mmol) under nitrogen, and the mixture was heated at reflux in an oil bath at 85° C. for 30 minutes. The reaction was cooled to room temperature and concentrated by rotary evaporation to a white solid. The crude material was purified by SiO2 flash chromatography (Alltech Extract-Clean™ column, 5 g bed) eluting with 5% methanol/CH2Cl2 to afford the title compound as a white solid (10 mg, 0.018 mmol, 71%). 1H NMR (400 MHz, DMSO-d6) δ ppm 0.50-0.60 (m, 1H), 0.80-0.93 (m, 1H), 0.99 (d, J=8.57 Hz, 2H), 1.69-1.85 (m, 2H), 2.34-2.43 (m, 1H), 2.59-2.66 (m, 2H), 3.17 (s, 3H), 3.66-3.87 (m, 2H), 7.09 (s, 1H), 7.18 (s, 1H), 7.26-7.45 (m, 3H), 7.88 (s, 1H), 8.02 (dd, J=8.89, 5.53 Hz, 2H), 11.99 (br s, 1H), 12.41 (s, 1H); MS (ESI+) m/z 538 (M+H)+, 1075 (2M+H)+; MS (ESI−) m/z 536 (M−H)−, 1073 (2M−H)−.

Workup

  1. temperaturethe mixture was heated
  2. temperatureThe reaction was cooled to room temperature
  3. concentrationconcentrated by rotary evaporation to a white solid
  4. customThe crude material was purified by SiO2 flash chromatography (Alltech Extract-Clean™ column, 5 g bed)
  5. washeluting with 5% methanol/CH2Cl2

Sources & evidence

ORD record
ord-77c7063efe094b3aa84920452f69688c
Source dataset
uspto-grants-2015_11
Patent number
US09173887B2

Reaction notes

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