Sodium Hydroxide → HCID 136344410, compound

HRID 1022444Notes

Reaction equation

HRID 1022444 reaction equation
C([O:3][C:4](=[O:28])[C:5]1[CH:10]=[CH:9][C:8]([N:11]2[CH2:16][CH2:15][N:14]([C:17]3[NH:18][C:19](=[O:27])[C:20]4[CH:25]=[CH:24][N:23]([CH3:26])[C:21]=4[N:22]=3)[CH2:13][CH2:12]2)=[CH:7][CH:6]=1)C.[OH-].[Na+]>O1CCCC1.CO.O>[CH3:26][N:23]1[C:21]2[N:22]=[C:17]([N:14]3[CH2:15][CH2:16][N:11]([C:8]4[CH:9]=[CH:10][C:5]([C:4]([OH:28])=[O:3])=[CH:6][CH:7]=4)[CH2:12][CH2:13]3)[NH:18][C:19](=[O:27])[C:20]=2[CH:25]=[CH:24]1

Participants

6

Reactant 2

HCID 14798Sodium Hydroxide2×HCID 136247063HCID 136247063, compound

Product 1

HCID 136344410HCID 136344410, compoundYield 128%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

A solution of 4-[4-(7-methyl-4-oxo-4,7-dihydro-3H-pyrrolo[2,3-d]pyrimidin-2-yl)-piperazin-1-yl]-benzoic acid ethyl ester (163 mg, 427 μmol) in tetrahydrofuran (1.6 mL) and methanol (0.8 mL) was treated with a 1N aqueous sodium hydroxide solution (748 μL, 748 μmol). The resulting yellow solution was stirred for 3 h at room temperature. At this point, another aliquot of a 1N aqueous sodium hydroxide solution (748 μL, 748 μmol) was added. At this time, the reaction was heated to 75° C. where it was stirred for 1.5 h. The reaction was then diluted with water (10 mL) and extracted with ethyl acetate (20 mL). The aqueous layer was acidified to pH 2 with a 1N aqueous hydrochloric acid solution and further extracted with ethyl acetate (20 mL). The organic layer was washed with a saturated aqueous sodium chloride solution (10 mL). Since product was not soluble in the organic layer, all of the layers were combined and concentrated in vacuo and dried to afford 4-(4-(7-methyl-4-oxo-4,7-dihydro-3H-pyrrolo[2,3-d]pyrimidin-2-yl)piperazin-1-yl)benzoic acid (193 mg, 128%) as a light grey solid. 1H NMR (300 MHz, DMSO-d6) δ ppm 3.41 (br. s., 4H) 3.57 (s, 3H) 3.71 (br. s., 4H) 6.25 (d, J=3.39 Hz, 1H) 6.78 (d, J=3.39 Hz, 1H) 7.02 (d, J=9.23 Hz, 2H) 7.79 (d, J=8.85 Hz, 2H) 10.89 (s, 1H) 12.29 (s, 1H). LC-MS calcd. for C18H20N5O3 [(M+H)+] 354, obsd. 354.1.

Workup

  1. temperatureAt this time, the reaction was heated to 75° C. where it
  2. stirringwas stirred for 1.5 h
  3. extractionextracted with ethyl acetate (20 mL)
  4. extractionfurther extracted with ethyl acetate (20 mL)
  5. washThe organic layer was washed with a saturated aqueous sodium chloride solution (10 mL)
  6. concentrationconcentrated in vacuo
  7. customdried

Sources & evidence

ORD record
ord-19b84da43e0348d59a21b31091af905f
Source dataset
uspto-grants-2014_05
Patent number
US08722661B2

Reaction notes

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