1,1'-Carbonyldiimidazole → N3-(3-ethyl-1-((6-methylpyridin-2-yl)methyl)-1H-indazol-4-yl)-N7-(pyrrolidin-3-yl)imidazo[1,2-a]pyridine-3,7-dicarboxamide

HRID 79356Notes

Reaction equation

HRID 79356 reaction equation
[CH2:1]([C:3]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][C:10]=2[NH:12][C:13]([C:15]2[N:19]3[CH:20]=[CH:21][C:22]([C:24](O)=[O:25])=[CH:23][C:18]3=[N:17][CH:16]=2)=[O:14])[N:5]([CH2:27][C:28]2[CH:33]=[CH:32][CH:31]=[C:30]([CH3:34])[N:29]=2)[N:4]=1)[CH3:2].N1(C(N2C=CN=C2)=O)C=CN=C1.[NH2:47][CH:48]1[CH2:52][CH2:51][N:50](C(OC(C)(C)C)=O)[CH2:49]1>CN(C=O)C>[CH2:1]([C:3]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][C:10]=2[NH:12][C:13]([C:15]2[N:19]3[CH:20]=[CH:21][C:22]([C:24]([NH:47][CH:48]4[CH2:52][CH2:51][NH:50][CH2:49]4)=[O:25])=[CH:23][C:18]3=[N:17][CH:16]=2)=[O:14])[N:5]([CH2:27][C:28]2[CH:33]=[CH:32][CH:31]=[C:30]([CH3:34])[N:29]=2)[N:4]=1)[CH3:2]

Participants

5

Reactant 3

HCID 682631,1'-CarbonyldiimidazoleHCID 27563701-Boc-3-aminopyrrolidineHCID 672601493-(3-ethyl-1-((6-methylpyridin-2-yl)methyl)-1H-indazol-4-ylcarbamoyl)imidazo[1,2-a]pyridine-7-carboxylic acid

Product 1

HCID 67259833N3-(3-ethyl-1-((6-methylpyridin-2-yl)methyl)-1H-indazol-4-yl)-N7-(pyrrolidin-3-yl)imidazo[1,2-a]pyridine-3,7-dicarboxamideYield 33.6%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To 3-(3-ethyl-1-((6-methylpyridin-2-yl)methyl)-1H-indazol-4-ylcarbamoyl) imidazo[1,2-a]pyridine-7-carboxylic acid (26 mg, 0.057 mmol; prepared as in Example 28, step A) in DMF (2 mL) was added di(1H-imidazol-1-yl)methanone (14 mg, 0.086 mmol). The reaction mixture was stirred at ambient temperature for 1 hour. tert-Butyl 3-aminopyrrolidine-1-carboxylate (32 mg, 0.17 mmol) was added to the reaction mixture. The mixture was sealed and heated at 70° C. for 2 hours and cooled to ambient temperature. DMF was removed under reduced pressure. The residue was triturated with Et2O. The resulting tan solid was dissolved in DCM (1 mL). TFA (1 mL) was added to the DCM solution. The reaction mixture was stirred for 30 minutes and then concentrated under reduced pressure. The residue was purified by silica gel chromatography (DCM/MeOH/NH4OH 10:1:0.1) to provide the final product (10 mg). MS (ES+APCI) m/z=523 (M+H).

Workup

  1. customThe mixture was sealed
  2. temperatureheated at 70° C. for 2 hours
  3. temperaturecooled to ambient temperature
  4. customDMF was removed under reduced pressure
  5. customThe residue was triturated with Et2O
  6. dissolutionThe resulting tan solid was dissolved in DCM (1 mL)
  7. additionTFA (1 mL) was added to the DCM solution
  8. stirringThe reaction mixture was stirred for 30 minutes
  9. concentrationconcentrated under reduced pressure
  10. customThe residue was purified by silica gel chromatography (DCM/MeOH/NH4OH 10:1:0.1)

Sources & evidence

ORD record
ord-868d519c42074148adddc6ee677cdd82
Source dataset
uspto-grants-2014_09
Patent number
US08841455B2

Reaction notes

Loading…