HCID 9842794, compound → HCID 23299452, compound

HRID 1952728Notes

Reaction equation

HRID 1952728 reaction equation
[CH3:1][Mg]Cl.[CH:4]([S:7]([N:10]1[C:14]2[CH:15]=[C:16]([C:19](=[O:28])[C:20]3[CH:25]=[C:24]([F:26])[CH:23]=[CH:22][C:21]=3[F:27])[CH:17]=[CH:18][C:13]=2[N:12]=[C:11]1[NH2:29])(=[O:9])=[O:8])([CH3:6])[CH3:5]>O1CCCC1>[NH2:29][C:11]1[N:10]([S:7]([CH:4]([CH3:6])[CH3:5])(=[O:8])=[O:9])[C:14]2[CH:15]=[C:16]([C:19]([C:20]3[CH:25]=[C:24]([F:26])[CH:23]=[CH:22][C:21]=3[F:27])([CH3:1])[OH:28])[CH:17]=[CH:18][C:13]=2[N:12]=1

Participants

4

Reactant 2

HCID 9842794HCID 9842794, compoundHCID 178418332HCID 178418332, compound2×

Product 1

HCID 23299452HCID 23299452, compoundYield 101.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Methyl magnesium chloride (929 mL, 2.79 mol, 3M in tetrahydrofuran) was added slowly over 30 minutes to a solution of 1-isopropylsulfonyl-2-amino-6-(2,5-difluorobenzoyl)benzimidazole (352.7 g, 0.929 mol) in tetrahydrofuran while maintaining the temperature between -20° C. and -30° C. When the addition was complete, the reaction mixture was warmed slowly to room temperature over 2 hours. Additional 3M methyl magnesium chloride (186 mL, followed by 46.5 mL) was added until less than 1% ketone starting material remained by HPLC analysis. The reaction was quenched by the sequential addition of ethyl acetate (4.2 L) and 1N hydrochloric acid (4.2 L) and the mixture stirred for 1 hour. The phases were separated and the aqueous phase extracted with ethyl acetate (2.0 L). The combined organic fractions were washed with brine (4.0 L) and dried over magnesium sulfate. After filtration, removal of the solvent by rotary evaporation afforded 373 g of the title compound as a beige foam (93% purity, 94% yield).

Workup

  1. temperaturewhile maintaining the temperature between -20° C. and -30° C
  2. additionWhen the addition
  3. customThe reaction was quenched by the sequential addition of ethyl acetate (4.2 L) and 1N hydrochloric acid (4.2 L)
  4. customThe phases were separated
  5. extractionthe aqueous phase extracted with ethyl acetate (2.0 L)
  6. washThe combined organic fractions were washed with brine (4.0 L)
  7. dry with materialdried over magnesium sulfate
  8. filtrationAfter filtration, removal of the solvent
  9. customby rotary evaporation

Sources & evidence

ORD record
ord-322460d252b143b58c85137ec681de19
Source dataset
uspto-grants-2000_09
Patent number
US06114327

Reaction notes

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