Sodium Hydroxide → 4-{[6-Cyclopropyl-3-(pyrimidin-5-ylamino)-pyridine-2-carbonyl]-amino}-1-methyl-1H-pyrazole-3-carboxylic acid

HRID 2368271Notes

Reaction equation

HRID 2368271 reaction equation
C[O:2][C:3]([C:5]1[C:9]([NH:10][C:11]([C:13]2[C:18]([NH:19][C:20]3[CH:21]=[N:22][CH:23]=[N:24][CH:25]=3)=[CH:17][CH:16]=[C:15]([CH:26]3[CH2:28][CH2:27]3)[N:14]=2)=[O:12])=[CH:8][N:7]([CH3:29])[N:6]=1)=[O:4].[OH-].[Na+]>CO.O>[CH:26]1([C:15]2[N:14]=[C:13]([C:11]([NH:10][C:9]3[C:5]([C:3]([OH:4])=[O:2])=[N:6][N:7]([CH3:29])[CH:8]=3)=[O:12])[C:18]([NH:19][C:20]3[CH:25]=[N:24][CH:23]=[N:22][CH:21]=3)=[CH:17][CH:16]=2)[CH2:28][CH2:27]1

Participants

5

Reactant 2

HCID 14798Sodium HydroxideHCID 700992004-{[6-Cyclopropyl-3-(pyrimidin-5-ylamino)-pyridine-2-carbonyl]-amino}-1-methyl-1H-pyrazole-3-carboxylic acid methyl ester

Product 1

HCID 701164844-{[6-Cyclopropyl-3-(pyrimidin-5-ylamino)-pyridine-2-carbonyl]-amino}-1-methyl-1H-pyrazole-3-carboxylic acidYield 49.3%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 962WaterSolvent

Procedure

To a stirred solution of 4-{[6-cyclopropyl-3-(pyrimidin-5-ylamino)-pyridine-2-carbonyl]-amino}-1-methyl-1H-pyrazole-3-carboxylic acid methyl ester (example 27, step 4; 300 mg, 0.76 mmol) in MeOH (7 ml) was added a solution of NaOH (49 mg, 1.2 mmol) in water (2 ml) while keeping the internal bath temperature below 5° C. The reaction mixture was stirred for 12 h at rt, then concentrated. The residue was dissolved in water (10 ml), and the aqueous layer was washed with EtOAc. The aqueous phase was acidified with aqueous 1N HCl solution (pH˜4-5), then saturated with sodium chloride, and extracted with EtOAc. Combined organic layers were washed with brine, dried (Na2SO4), and filtered. The organic layer was concentrated to give the title compound (142 mg, 45%) as yellowish sticky solid, which was directly used for next step.

Workup

  1. customthe internal bath temperature below 5° C
  2. concentrationconcentrated
  3. dissolutionThe residue was dissolved in water (10 ml)
  4. washthe aqueous layer was washed with EtOAc
  5. extractionsaturated with sodium chloride, and extracted with EtOAc
  6. washCombined organic layers were washed with brine
  7. dry with materialdried (Na2SO4)
  8. filtrationfiltered
  9. concentrationThe organic layer was concentrated

Sources & evidence

ORD record
ord-84a66df6effc4704af7ea39241a33526
Source dataset
uspto-grants-2014_04
Patent number
US08703768B2

Reaction notes

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