Sodium hydride → HCID 89996303, compound

HRID 1480842Notes

Reaction equation

HRID 1480842 reaction equation
[CH3:1][C:2]1[CH:7]=[C:6]([C:8]2[CH:9]=[N:10][N:11]([CH3:13])[CH:12]=2)[CH:5]=[CH:4][C:3]=1[NH:14][CH:15]=O.[H-].[Na+].[Cl:19][C:20]1[C:25]2[N:26]=C(S(C)(=O)=O)[N:28]=[CH:29][C:24]=2[CH:23]=[CH:22][N:21]=1>C1COCC1>[Cl:19][C:20]1[C:25]2[N:26]=[C:15]([NH:14][C:3]3[CH:4]=[CH:5][C:6]([C:8]4[CH:9]=[N:10][N:11]([CH3:13])[CH:12]=4)=[CH:7][C:2]=3[CH3:1])[N:28]=[CH:29][C:24]=2[CH:23]=[CH:22][N:21]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 89996157HCID 89996157, compoundHCID 89996299HCID 89996299, compound

Product 1

HCID 89996303HCID 89996303, compoundYield 121.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a cooled (0° C.) suspension of N-(2-methyl-4-(1-methyl-1H-pyrazol-4-yl)phenyl)formamide (Preparation 99, 40 mg, 0.186 mmol) in THF (4 mL) was added NaH (60% dispersion in oil, 12 mg, 0.297 mmol). The reaction mixture was stirred at room temperature for 10 minutes. The reaction mixture was cooled to 0° C. and 8-chloro-2-(methylsulfonyl)pyrido[3,4-d]pyrimidine (Preparation 97, 59 mg, 0.242 mmol) was added. The reaction mixture was stirred for 18 hours, whilst slowly warming to room temperature. The reaction mixture was concentrated in vacuo. The residue was partitioned between EtOAc (30 mL) and water (30 mL). The aqueous layer was extracted with EtOAc (30 mL) and DCM (30 mL). The combined organic layers were washed with water (30 mL) and brine (30 mL), dried (MgSO4) and concentrated in vacuo. The residue was purified by silica gel column chromatography eluting with 0-5% MeOH in EtOAc to give the title compound (79 mg, 97%).

Workup

  1. temperatureTo a cooled
  2. temperatureThe reaction mixture was cooled to 0° C.
  3. stirringThe reaction mixture was stirred for 18 hours
  4. temperaturewhilst slowly warming to room temperature
  5. concentrationThe reaction mixture was concentrated in vacuo
  6. customThe residue was partitioned between EtOAc (30 mL) and water (30 mL)
  7. extractionThe aqueous layer was extracted with EtOAc (30 mL) and DCM (30 mL)
  8. washThe combined organic layers were washed with water (30 mL) and brine (30 mL)
  9. dry with materialdried (MgSO4)
  10. concentrationconcentrated in vacuo
  11. customThe residue was purified by silica gel column chromatography
  12. washeluting with 0-5% MeOH in EtOAc

Sources & evidence

ORD record
ord-4e2b4f11041d4625b1a1313e3572b111
Source dataset
uspto-grants-2016_08
Patent number
US09409907B2

Reaction notes

Loading…