Methanol → HCID 52920205, compound

HRID 1615390Notes

Reaction equation

HRID 1615390 reaction equation
C(OC[N:9]1[C:13]2[N:14]=[CH:15][N:16]=[C:17]([N:18]3[C:26]4[C:21](=[CH:22][CH:23]=[C:24]([C:27]5[CH:32]=[CH:31][CH:30]=[C:29]([NH2:33])[CH:28]=5)[CH:25]=4)[CH:20]=[CH:19]3)[C:12]=2[CH:11]=[CH:10]1)(=O)C(C)(C)C.[N:34]([C:37]1[CH:42]=[CH:41][CH:40]=[CH:39][C:38]=1[O:43][CH3:44])=[C:35]=[O:36].[OH-].[Na+].CO>C1COCC1.O.C(OCC)(=O)C>[N:14]1[C:13]2[NH:9][CH:10]=[CH:11][C:12]=2[C:17]([N:18]2[C:26]3[C:21](=[CH:22][CH:23]=[C:24]([C:27]4[CH:28]=[C:29]([NH:33][C:35]([NH:34][C:37]5[CH:42]=[CH:41][CH:40]=[CH:39][C:38]=5[O:43][CH3:44])=[O:36])[CH:30]=[CH:31][CH:32]=4)[CH:25]=3)[CH:20]=[CH:19]2)=[N:16][CH:15]=1

Participants

8

Reactant 4

HCID 887MethanolHCID 14798Sodium HydroxideHCID 69695Benzene, 1-isocyanato-2-methoxy-HCID 67203834HCID 67203834, compound

Product 1

HCID 52920205HCID 52920205, compoundYield 75%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
50 °C

Procedure

(4-(6-(3-Aminophenyl)-1H-indol-1-yl)-7H-pyrrolo[2,3-d]pyrimidin-7-yl)methyl pivalate (30 mg, 0.068 mmol) was dissolved in THF (1 mL). At room temperature, 1-isocyanato-2-methoxybenzene (32.6 μL, 0.25 mmol) was added. The reaction mixture was stirred at 50° C. for 3 hours and cooled to room temperature. After adding 1 N NaOH (1 mL) and MeOH (1 mL), the mixture solution was stirred at room temperature for 2 hours. After adding ethyl acetate and water, the organic layer was separated. The aqueous layer was extracted with ethyl acetate and the combined organic layer was washed with brine, dried with magnesium sulfate, and concentrated under reduced pressure. Purification of the residue by column chromatography (silica gel, DCM:MeOH=20:1) yielded 1-(3-(1-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-indol-6-yl)phenyl)-3-(2-methoxyphenyl)urea (24.3 mg, 0.051 mmol) as white solid.

Workup

  1. temperaturecooled to room temperature
  2. stirringthe mixture solution was stirred at room temperature for 2 hours
  3. customthe organic layer was separated
  4. extractionThe aqueous layer was extracted with ethyl acetate
  5. washthe combined organic layer was washed with brine
  6. dry with materialdried with magnesium sulfate
  7. concentrationconcentrated under reduced pressure
  8. customPurification of the residue by column chromatography (silica gel, DCM:MeOH=20:1)

Sources & evidence

ORD record
ord-c940721ae92047938fd73b230ae75198
Source dataset
uspto-grants-2014_07
Patent number
US08765749B2

Reaction notes

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