Sodium hydride → 6-Amino-7-(4-fluorobenzyl)-2-[3-(2-fluorobenzyl)-1H-pyrazolo[4,3-b]pyridin-1-yl]-7,9-dihydro-8H-purin-8-one

HRID 510107Notes

Reaction equation

HRID 510107 reaction equation
[NH2:1][C:2]1[C:7]([N:8]([CH2:13][C:14]2[CH:19]=[CH:18][C:17]([F:20])=[CH:16][CH:15]=2)[C:9](=O)[O:10]C)=[C:6]([NH2:21])[N:5]=[C:4]([N:22]2[C:30]3[C:25](=[N:26][CH:27]=[CH:28][CH:29]=3)[C:24]([CH2:31][C:32]3[CH:37]=[CH:36][CH:35]=[CH:34][C:33]=3[F:38])=[N:23]2)[N:3]=1.[H-].[Na+].C(=O)([O-])O.[Na+]>O1CCCC1>[NH2:1][C:2]1[N:3]=[C:4]([N:22]2[C:30]3[C:25](=[N:26][CH:27]=[CH:28][CH:29]=3)[C:24]([CH2:31][C:32]3[CH:37]=[CH:36][CH:35]=[CH:34][C:33]=3[F:38])=[N:23]2)[N:5]=[C:6]2[C:7]=1[N:8]([CH2:13][C:14]1[CH:19]=[CH:18][C:17]([F:20])=[CH:16][CH:15]=1)[C:9](=[O:10])[NH:21]2

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 516892Sodium BicarbonateHCID 57330719Methyl {4,6-diamino-2-[3-(2-fluorobenzyl)-1H-pyrazolo[4,3-b]pyridin-1-yl]pyrimidin-5-yl}(4-fluorobenzyl)carbamate

Product 1

HCID 569289446-Amino-7-(4-fluorobenzyl)-2-[3-(2-fluorobenzyl)-1H-pyrazolo[4,3-b]pyridin-1-yl]-7,9-dihydro-8H-purin-8-one

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
65 °C

Procedure

21 mg (0.04 mmol) of the compound from example 50A were initially charged in tetrahydrofuran (1.0 ml), 1.8 mg (0.04 mmol) of sodium hydride (60% in mineral oil) were added and the mixture was stirred at 65° C. for 30 min. The reaction mixture was admixed with saturated aqueous sodium hydrogencarbonate solution and extracted twice with ethyl acetate. The combined organic phases were dried over sodium sulfate, filtered and concentrated by rotary evaporation. The residue was separated by means of preparative HPLC (eluent: acetonitrile-water with 0.1% formic acid gradient) and the product fractions were concentrated. This gave 8.5 mg (44% of theory) of the title compound in solid form.

Workup

  1. extractionextracted twice with ethyl acetate
  2. dry with materialThe combined organic phases were dried over sodium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated by rotary evaporation
  5. customThe residue was separated by means of preparative HPLC (eluent: acetonitrile-water with 0.1% formic acid gradient)
  6. concentrationthe product fractions were concentrated

Sources & evidence

ORD record
ord-62178f1627f846bb9d04ba53f261a0b0
Source dataset
uspto-grants-2015_08
Patent number
US09096592B2

Reaction notes

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