Tetrahydrofuran → HCID 178464308, compound

HRID 2274393Notes

Reaction equation

HRID 2274393 reaction equation
[CH:1]([N:4]([CH2:8]C)[CH:5](C)C)(C)C.F[C:11](F)(F)[C:12]([OH:14])=O.[CH2:17]([N:19]([CH2:47][CH3:48])[C:20]([NH:22][C:23]1[C:24]([C:28]2[NH:32][C:31]3[CH:33]=[C:34]([O:38][CH2:39][CH2:40]N4CCCCC4)[C:35]([F:37])=[CH:36][C:30]=3[N:29]=2)=[N:25][NH:26][CH:27]=1)=[O:21])[CH3:18].[CH2:49]1[CH2:53]OC[CH2:50]1>>[CH3:8][N:4]([CH3:1])[CH2:5][CH2:40][CH2:39][O:38][C:34]1[C:35]([F:37])=[CH:36][C:30]2[N:29]=[C:28]([C:24]3[C:23]([NH:22][C:20](=[O:21])[N:19]([CH2:17][CH3:18])[CH2:47][CH3:48])=[CH:27][N:26]([CH:12]4[CH2:11][CH2:53][CH2:49][CH2:50][O:14]4)[N:25]=3)[NH:32][C:31]=2[CH:33]=1

Participants

4

Reactant 3

HCID 8028TetrahydrofuranHCID 81531DiisopropylethylamineHCID 178464319HCID 178464319, compound

Product 1

HCID 178464308HCID 178464308, compound

Conditions

Temperature
52 °C

Procedure

1.4 mL of diethylcarbonyl chloride and 1.8 mL of N,N-diisopropylethylamine are added to a solution of 0.9 g of intermediate 1 in 30 mL of THF. The reaction mixture is heated at 52° C. for 24 hours. The reaction medium is cooled to ambient temperature and washed with 30 mL of a saturated solution of sodium bicarbonate. The aqueous phase is extracted with three times 30 mL of EtOAc. The organic phases are dried over MgSO4, filtered and concentrated under vacuum in a rotary evaporator. 1.4 g of 3-[3-[6-(3-dimethylaminopropoxy)-5-fluoro-1H-benzimidazol-2-yl]-1-(tetrahydropyran-2-yl)-1H-pyrazol-4-yl]-1,1-diethylurea are obtained in the form of a brown oil. 1H NMR (300 MHz, DMSO-d6, δ in ppm): 1.22 (t, J=7.5 Hz, 6H); from 1.50 to 2.22 (m, 8H); 2.85 (s, 6H); 3.27 (m, 2H); from 3.31 to 3.48 (m, 4H); 3.67 (m, 1H); 3.97 (m, 1H); 4.17 (t, J=6.0 Hz, 2H); 5.47 (dd, J=2.5 and 10.0 Hz, 1H); 7.22 (d, J=8.0 Hz, 1H); 7.44 (d, J=11.0 Hz, 1H); 8.14 (s, 1H).

Workup

  1. temperatureThe reaction medium is cooled to ambient temperature
  2. washwashed with 30 mL of a saturated solution of sodium bicarbonate
  3. extractionThe aqueous phase is extracted with three times 30 mL of EtOAc
  4. dry with materialThe organic phases are dried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated under vacuum in a rotary evaporator

Sources & evidence

ORD record
ord-a9d8f2980b4148a585ffcfd09d61355f
Source dataset
uspto-grants-2015_09
Patent number
US09126969B2

Reaction notes

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