N-methyl-2-pyrrolidone → 4-[4-({3-chloro-4-[(3-fluorobenzyl)oxy]phenyl}amino)-5H-pyrrolo[3,2-d]pyrimidin-6-yl]benzoic acid hydrochloride

HRID 1926028Notes

Reaction equation

HRID 1926028 reaction equation
Cl.[Cl:2][C:3]1[C:4]2[NH:11][C:10]([C:12]3[CH:22]=[CH:21][C:15]([C:16]([O:18]CC)=[O:17])=[CH:14][CH:13]=3)=[CH:9][C:5]=2[N:6]=[CH:7][N:8]=1.[Cl:23][C:24]1[CH:25]=[C:26]([CH:28]=[CH:29][C:30]=1[O:31][CH2:32][C:33]1[CH:38]=[CH:37][CH:36]=[C:35]([F:39])[CH:34]=1)[NH2:27].CN1CCCC1=O.C(=O)([O-])O.[Na+]>O>[ClH:2].[Cl:23][C:24]1[CH:25]=[C:26]([NH:27][C:3]2[C:4]3[NH:11][C:10]([C:12]4[CH:13]=[CH:14][C:15]([C:16]([OH:18])=[O:17])=[CH:21][CH:22]=4)=[CH:9][C:5]=3[N:6]=[CH:7][N:8]=2)[CH:28]=[CH:29][C:30]=1[O:31][CH2:32][C:33]1[CH:38]=[CH:37][CH:36]=[C:35]([F:39])[CH:34]=1

Participants

6

Reactant 4

HCID 13387N-methyl-2-pyrrolidoneHCID 516892Sodium BicarbonateHCID 70592633-Chloro-4-(3-fluorobenzyloxy)anilineHCID 86615760ethyl 4-(4-chloro-5H-pyrrolo[3,2-d]pyrimidin-6-yl)benzoate hydrochloride

Product 1

HCID 675206604-[4-({3-chloro-4-[(3-fluorobenzyl)oxy]phenyl}amino)-5H-pyrrolo[3,2-d]pyrimidin-6-yl]benzoic acid hydrochlorideYield 62%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
140 °C

Procedure

A mixture of ethyl 4-(4-chloro-5H-pyrrolo[3,2-d]pyrimidin-6-yl)benzoate hydrochloride (517 mg), 3-chloro-4-[(3-fluorobenzyl)oxy]aniline (462 mg) and 1-methyl-2-pyrrolidinone (8 mL) was stirred at 140° C. for 5 hrs, poured into water (40 mL), and adjusted to pH 8 with saturated aqueous sodium hydrogen carbonate. The precipitated solid was collected by filtration, washed with water and suspended in methanol (15 mL). After stirring at room temperature for 30 min, the solid was collected by filtration and dried under reduced pressure at 60° C. The obtained solid was suspended in ethanol (10 mL) and 1N aqueous sodium hydroxide solution (1.5 mL) was added. After stirring at room temperature for 6.5 hrs, and at 60° C. for 3.5 hrs, the mixture was cooled to room temperature. 1N Hydrochloric acid (155 mL) was added, and the precipitated solid was collected by filtration, washed with water and dried under reduced pressure at 60° C. to give the title compound (498 mg).

Workup

  1. filtrationThe precipitated solid was collected by filtration
  2. washwashed with water
  3. stirringAfter stirring at room temperature for 30 min
  4. filtrationthe solid was collected by filtration
  5. customdried under reduced pressure at 60° C
  6. addition1N aqueous sodium hydroxide solution (1.5 mL) was added
  7. stirringAfter stirring at room temperature for 6.5 hrs
  8. waitat 60° C. for 3.5 hrs
  9. temperaturethe mixture was cooled to room temperature
  10. addition1N Hydrochloric acid (155 mL) was added
  11. filtrationthe precipitated solid was collected by filtration
  12. washwashed with water
  13. customdried under reduced pressure at 60° C.

Sources & evidence

ORD record
ord-5359cf9495684a5db3b9d56e610b38ce
Source dataset
uspto-grants-2012_05
Patent number
US08178543B2

Reaction notes

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