Sodium Hydroxide → HCID 89995981, compound

HRID 1480782Notes

Reaction equation

HRID 1480782 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[C:7]([C:9]2[CH:10]=[N:11][N:12]([CH3:14])[CH:13]=2)[CH:6]=[CH:5][C:4]=1[NH:15][CH:16]=O.[H-].[Na+].[Cl:20][C:21]1[C:26]2[N:27]=C(S(C)(=O)=O)[N:29]=[CH:30][C:25]=2[CH:24]=[CH:23][N:22]=1.[OH-].[Na+]>C1COCC1.CO>[Cl:20][C:21]1[C:26]2[N:27]=[C:16]([NH:15][C:4]3[CH:5]=[CH:6][C:7]([C:9]4[CH:10]=[N:11][N:12]([CH3:14])[CH:13]=4)=[CH:8][C:3]=3[O:2][CH3:1])[N:29]=[CH:30][C:25]=2[CH:24]=[CH:23][N:22]=1

Participants

7

Reactant 4

HCID 14798Sodium HydroxideHCID 24758Sodium hydrideHCID 89996157HCID 89996157, compoundHCID 89996185HCID 89996185, compound

Product 1

HCID 89995981HCID 89995981, compoundYield 79%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

A solution of N-(2-methoxy-4-(1-methyl-1H-pyrazol-4-yl)phenyl)formamide (Preparation 56, 24 mg, 0.104 mmol) in THF (1 mL) was treated with sodium hydride (7 mg, 0.175 mmol) at 0° C. After stirring for 20 minutes at room temperature the mixture was cooled to 0° C. and 8-chloro-2-(methylsulfonyl)pyrido[3,4-d]pyrimidine (Preparation 97, 33 mg, 0.135 mmol) was added. The reaction was allowed to reach room temperature and stirred for 18 hours. Aqueous NaOH (2M, 0.5 mL) and MeOH (0.5 mL) were added and the resulting mixture stirred for 1 hour. The volatiles were removed under reduced pressure and the residue was partitioned between EtOAc and water. The aqueous layer was extracted with EtOAc and the combined organic layers were washed with water, brine, dried and concentrated. The residue was purified by silica gel column chromatography eluting with 0 to 80% EtOAc in cyclohexane to give the title compound (30 mg, 79%).

Workup

  1. temperaturewas cooled to 0° C.
  2. customto reach room temperature
  3. stirringstirred for 18 hours
  4. stirringthe resulting mixture stirred for 1 hour
  5. customThe volatiles were removed under reduced pressure
  6. customthe residue was partitioned between EtOAc and water
  7. extractionThe aqueous layer was extracted with EtOAc
  8. washthe combined organic layers were washed with water, brine
  9. customdried
  10. concentrationconcentrated
  11. customThe residue was purified by silica gel column chromatography
  12. washeluting with 0 to 80% EtOAc in cyclohexane

Sources & evidence

ORD record
ord-60d6dc8a1e814cb39af9eba827c3aee2
Source dataset
uspto-grants-2016_08
Patent number
US09409907B2

Reaction notes

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