Water → HCID 58931319, compound

HRID 387936Notes

Reaction equation

HRID 387936 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([NH:8][C:9]([NH:11][C:12]2[CH:17]=[CH:16][C:15]([O:18][C:19]3[C:20]4[CH:27]=[C:26]([C:28]5[CH:33]=[CH:32][C:31]([OH:34])=[CH:30][CH:29]=5)[NH:25][C:21]=4[N:22]=[CH:23][N:24]=3)=[CH:14][CH:13]=2)=[O:10])[CH:5]=[CH:6][CH:7]=1.Cl.Cl[CH2:37][CH2:38][N:39]([CH2:42][CH3:43])[CH2:40][CH3:41].C(=O)(O)[O-].[K+].O>CN(C)C=O>[CH2:38]([N:39]([CH2:42][CH3:43])[CH2:40][CH2:41][O:34][C:31]1[CH:30]=[CH:29][C:28]([C:26]2[NH:25][C:21]3[N:22]=[CH:23][N:24]=[C:19]([O:18][C:15]4[CH:14]=[CH:13][C:12]([NH:11][C:9]([NH:8][C:4]5[CH:5]=[CH:6][CH:7]=[C:2]([F:1])[CH:3]=5)=[O:10])=[CH:17][CH:16]=4)[C:20]=3[CH:27]=2)=[CH:33][CH:32]=1)[CH3:37]

Participants

6

Reactant 4

HCID 962WaterHCID 133631-Chloro-2-(diethylamine)ethane hydrochloride2×HCID 516893Potassium Bicarbonate2×HCID 58930969HCID 58930969, compound

Product 1

HCID 58931319HCID 58931319, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Conditions

Temperature
55 °C

Procedure

After dissolving 114 mg of 1-(3-fluorophenyl)-3-{-4-[6-(4-hydroxyphenyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yloxy]phenyl}urea in 2 ml of dimethylformamide, there were added 44 mg (ca. 1 equivalent) of 2-chloroethyldiethylamine hydrochloride and 63 mg (2.5 equivalents) of potassium bicarbonate, and the mixture was stirred at 50-60° C. for 16 hours. There were then added 17 mg of 2-chloroethyldiethylamine hydrochloride, 20 mg of potassium bicarbonate and 1 ml of dimethylformamide, and the mixture was stirred overnight at the same temperature. It was then returned to room temperature, water was added, and liquid separation and extraction were performed with ethyl acetate-tetrahydrofuran. The organic layer was washed with water and saturated saline, concentrated and subjected to NH silica gel column chromatography (hexane-ethyl acetate) to obtain 33 mg of a crude solid containing the title compound. This was washed with ethyl acetate to obtain 5 mg of the title compound.

Workup

  1. stirringthe mixture was stirred overnight at the same temperature
  2. customwas then returned to room temperature
  3. customliquid separation and extraction
  4. washThe organic layer was washed with water and saturated saline
  5. concentrationconcentrated
  6. customto obtain 33 mg of a crude solid

Sources & evidence

ORD record
ord-7883d8bd04de473292765f3ea868188f
Source dataset
uspto-grants-2013_02
Patent number
US08372981B2

Reaction notes

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