Ethyl isocyanate → HCID 67975475, compound

HRID 45804Notes

Reaction equation

HRID 45804 reaction equation
Cl.[NH2:2][CH:3]1[CH2:8][CH2:7][CH:6]([N:9]2[C:21]3[C:20]4[N:19]=[C:18]([S:22][CH3:23])[N:17]=[CH:16][C:15]=4[CH:14]=[CH:13][C:12]=3[C:11]([C:24]([NH2:26])=[O:25])=[N:10]2)[CH2:5][CH2:4]1.[CH2:27]([N:29]=[C:30]=[O:31])[CH3:28].CCN(C(C)C)C(C)C.C([O-])(O)=O.[Na+]>CN(C)C=O.C(OCC)(=O)C>[CH2:27]([NH:29][C:30]([NH:2][CH:3]1[CH2:8][CH2:7][CH:6]([N:9]2[C:21]3[C:20]4[N:19]=[C:18]([S:22][CH3:23])[N:17]=[CH:16][C:15]=4[CH:14]=[CH:13][C:12]=3[C:11]([C:24]([NH2:26])=[O:25])=[N:10]2)[CH2:5][CH2:4]1)=[O:31])[CH3:28]

Participants

7

Reactant 4

HCID 8022Ethyl isocyanateHCID 81531DiisopropylethylamineHCID 516892Sodium BicarbonateHCID 67975581HCID 67975581, compound

Product 1

HCID 67975475HCID 67975475, compoundYield 11.1%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
100 °C

Procedure

30 mg (0.084 mmol) of 1-(4-aminocyclohexyl)-8-(methylsulfanyl)-1H-pyrazolo[4,3-h]quinazoline-3-carboxamide hydrochloride were dissolved in 2 ml of dimethylformamide. To the obtained solution 32 μl (0.42 mmol) of ethylisocyanate, 60 μl (0.336 mmol) of DIPEA, were added. The mixture was stirred at 100° C. for 18 hours, the solution was portioned between ethyl acetate and saturated aqueous solution of NaHCO3, and the organic layer was washed with brine, dried over Na2SO4 and evaporated under vacuum. The crude was purified by silica gel chromatography (DCM/MeOH/NH4OH 95/5/1) to provide 1-{4-[(ethylcarbamoyl)amino]cyclohexyl}-8-(methylsulfanyl)-1H-pyrazolo[4,3-h]quinazoline-3-carboxamide 4 mg (11%) as a white solid. LC/MS (254) HPLC method 2 Rt 4.38 min. 1H NMR (401 MHz, DMSO-d6) δ 9.47 (s, 1H), 8.27 (d, J=8.67 Hz, 1H), 7.74 (d, J=8.67 Hz, 1H), 7.59 (s, 2H), 6.06 (d, J=7.08 Hz, 1H), 5.89-6.02 (m, 1H), 5.81 (t, J=5.49 Hz, 1H), 3.78-3.88 (m, 1H), 3.00-3.07 (m, 2H), 2.71-2.74 (m, 3H), 2.15-2.29 (m, 2H), 1.99-2.11 (m, 3H), 1.90 (dd, J=3.54, 13.67 Hz, 2H), 1.65-1.79 (m, 2H), 1.01 (t, J=7.20 Hz, 3H). HRMS (ESI) calcd for C20H25N7O2S [M+H]+ 428.1863 found 428.1852.

Workup

  1. washthe organic layer was washed with brine
  2. dry with materialdried over Na2SO4
  3. customevaporated under vacuum
  4. customThe crude was purified by silica gel chromatography (DCM/MeOH/NH4OH 95/5/1)

Sources & evidence

ORD record
ord-be75089198f94cfabbc6c1ce3b37938b
Source dataset
uspto-grants-2013_09
Patent number
US08541576B2

Reaction notes

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