Sodium hydride → HCID 10196736, compound

HRID 2245826Notes

Reaction equation

HRID 2245826 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]2[C:9](=[C:10]([CH3:12])[CH:11]=1)[NH:8][C:7](=[O:13])[N:6]([CH:14]([CH3:16])[CH3:15])[C:5]2=[O:17].[H-].[Na+].[Br:20][C:21]1[CH:25]=[C:24]([C:26](O)=[O:27])[N:23]([C:29]2[C:34]([Cl:35])=[CH:33][CH:32]=[CH:31][N:30]=2)[N:22]=1.C(Cl)(=O)C(Cl)=O>CN(C)C=O.ClCCl>[Br:1][C:2]1[CH:3]=[C:4]2[C:9](=[C:10]([CH3:12])[CH:11]=1)[N:8]([C:26]([C:24]1[N:23]([C:29]3[C:34]([Cl:35])=[CH:33][CH:32]=[CH:31][N:30]=3)[N:22]=[C:21]([Br:20])[CH:25]=1)=[O:27])[C:7](=[O:13])[N:6]([CH:14]([CH3:15])[CH3:16])[C:5]2=[O:17]

Participants

8

Reactant 4

HCID 24758Sodium hydrideHCID 65578Oxalyl chlorideHCID 115875353-Bromo-1-(3-chloropyridin-2-yl)-1H-pyrazole-5-carboxylic acidHCID 68545554HCID 68545554, compound

Product 1

HCID 10196736HCID 10196736, compound

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideCatalystHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of the quinazolinedione of Step G (245 mg, 0.825 mmol) in dimethylformamide (5 mL) was added sodium hydride (60% oil dispersion, 36 mg, 0.90 mmol) and the reaction was allowed to stir at room temperature. In a separate reaction flask containing a solution of the pyrazole acid of Step D (500 mg, 1.65 mmol) in dichloromethane (10 mL) was added oxalyl chloride (0.17 mL, 1.95 mmol) and one drop of DMF. This mixture was stirred for 2 hours, then concentrated and placed under vacuum. The acid chloride was divided into two equal portions. One of these portions was taken up in 5 mL of DMF and added to the quinazolinedione/NaH reaction mixture and the resulting mixture was stirred at room temperature for 3 hours. The reaction was partitioned between ethyl acetate and water, washed twice with water, then with brine and dried over sodium sulfate. The crude product was purified by chromatography on silica gel with 99:1 chloroform/acetone as eluent to afford the title compound, a compound of the present invention.

Workup

  1. customIn a separate reaction flask
  2. stirringThis mixture was stirred for 2 hours
  3. concentrationconcentrated
  4. additionadded to the quinazolinedione/NaH reaction mixture
  5. stirringthe resulting mixture was stirred at room temperature for 3 hours
  6. customThe reaction was partitioned between ethyl acetate and water
  7. washwashed twice with water
  8. dry with materialwith brine and dried over sodium sulfate
  9. customThe crude product was purified by chromatography on silica gel with 99:1 chloroform/acetone as eluent

Sources & evidence

ORD record
ord-ced5035526ee43a8ac950ee79a167ecc
Source dataset
uspto-grants-2010_03
Patent number
US07683201B2

Reaction notes

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