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

HRID 2368247Notes

Reaction equation

HRID 2368247 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-6b304fbbf41143e4a8d89bfb90870d6f
Source dataset
uspto-grants-2014_04
Patent number
US08703768B2

Reaction notes

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