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

HRID 467650Notes

Reaction equation

HRID 467650 reaction equation
C[CH2:2][N:3]=[C:4]=[N:5]CCCN(C)C.[CH:12]1[CH:13]=[CH:14][C:15]2[N:20](O)N=N[C:16]=2[CH:17]=1.[CH3:22][O:23][C:24]([C:26]1[C:30]([NH2:31])=[CH:29][N:28]([CH3:32])[N:27]=1)=[O:25].C([N:35]([CH2:38][CH3:39])[CH2:36][CH3:37])C.CN([CH:43]=[O:44])C>>[CH3:22][O:23][C:24]([C:26]1[C:30]([NH:31][C:43]([C:39]2[C:38]([NH:35][C:36]3[CH:37]=[N:5][CH:4]=[N:3][CH:2]=3)=[CH:17][CH:16]=[C:15]([CH:14]3[CH2:13][CH2:12]3)[N:20]=2)=[O:44])=[CH:29][N:28]([CH3:32])[N:27]=1)=[O:25]

Participants

6

Reactant 5

HCID 6228DimethylformamideHCID 8471TriethylamineHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 7017722methyl 4-amino-1-methyl-1H-pyrazole-3-carboxylate

Product 1

HCID 700992004-{[6-Cyclopropyl-3-(pyrimidin-5-ylamino)-pyridine-2-carbonyl]-amino}-1-methyl-1H-pyrazole-3-carboxylic acid methyl esterYield 69%

Procedure

To a stirred solution of A-2 (600 mg, 2.34 mmol) in DMF (10 ml) was added EDCI (672 mg, 3.51 mmol) and HOBt (538 mg, 3.51 mmol) at 25° C. Stirring was continued for 10 min. 4-Amino-1-methyl-1H-pyrazole-3-carboxylic acid methyl ester (362 mg, 2.35 mmol) and triethylamine (0.8 ml, 5.35 mmol) were subsequently added to the above solution. The reaction mixture was stirred at 25° C. overnight, then quenched with water (8 ml), and extracted with CH2Cl2. The combined organic layers were washed with brine, dried (Na2SO4), filtered, and evaporated. The crude product thus obtained was purified by column chromatography over silica gel (2% MeOH/CH2Cl2) to provide the title compound (642 mg, 69%) as yellow sticky solid.

Workup

  1. stirringThe reaction mixture was stirred at 25° C. overnight
  2. customquenched with water (8 ml)
  3. extractionextracted with CH2Cl2
  4. washThe combined organic layers were washed with brine
  5. dry with materialdried (Na2SO4)
  6. filtrationfiltered
  7. customevaporated
  8. customThe crude product thus obtained
  9. customwas purified by column chromatography over silica gel (2% MeOH/CH2Cl2)

Sources & evidence

ORD record
ord-b78b5a48fed941d9a5eb2eba81dbeeb9
Source dataset
uspto-grants-2014_01
Patent number
US08623866B2

Reaction notes

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