Triethylamine → N-(5-((2-(2,2-Dimethylpyrrolidin-1-yl)ethyl)carbamoyl)-2-fluorophenyl)-7-(1-methyl-1H-pyrazol-4-yl)imidazo[1,2-a]pyridine-3-carboxamide

HRID 335291Notes

Reaction equation

HRID 335291 reaction equation
[F:1][C:2]1[CH:10]=[CH:9][C:5]([C:6](O)=[O:7])=[CH:4][C:3]=1[NH:11][C:12]([C:14]1[N:18]2[CH:19]=[CH:20][C:21]([C:23]3[CH:24]=[N:25][N:26]([CH3:28])[CH:27]=3)=[CH:22][C:17]2=[N:16][CH:15]=1)=[O:13].[CH3:29][C:30]1([CH3:38])[CH2:34][CH2:33][CH2:32][N:31]1[CH2:35][CH2:36][NH2:37].C(N(CC)CC)C.C(P1(=O)OP(CCC)(=O)OP(CCC)(=O)O1)CC>CN(C=O)C.CCOC(C)=O.CO.CCOC(C)=O>[CH3:29][C:30]1([CH3:38])[CH2:34][CH2:33][CH2:32][N:31]1[CH2:35][CH2:36][NH:37][C:6]([C:5]1[CH:9]=[CH:10][C:2]([F:1])=[C:3]([NH:11][C:12]([C:14]2[N:18]3[CH:19]=[CH:20][C:21]([C:23]4[CH:24]=[N:25][N:26]([CH3:28])[CH:27]=4)=[CH:22][C:17]3=[N:16][CH:15]=2)=[O:13])[CH:4]=1)=[O:7]

Participants

8

Reactant 4

HCID 8471TriethylamineHCID 111923Propylphosphonic anhydrideHCID 451570772-(2,2-Dimethylpyrrolidin-1-yl)ethan-1-amineHCID 712830924-Fluoro-3-(7-(1-methyl-1H-pyrazol-4-yl)imidazo[1,2-a]pyridine-3-carboxamido)benzoic Acid

Product 1

HCID 71283395N-(5-((2-(2,2-Dimethylpyrrolidin-1-yl)ethyl)carbamoyl)-2-fluorophenyl)-7-(1-methyl-1H-pyrazol-4-yl)imidazo[1,2-a]pyridine-3-carboxamide

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolventHCID 21584119Ethylacetate methanolSolvent

Procedure

A solution of 4-fluoro-3-(7-(1-methyl-1H-pyrazol-4-yl)imidazo[1,2-a]pyridine-3-carboxamido)benzoic acid (step 1) (6.31 g, 16.63 mmol), 2-(2,2-dimethylpyrrolidin-1-yl)ethanamine (2.84 g, 19.96 mmol) and triethylamine (6.96 ml, 49.9 mmol) in DMF (36.9 ml) and EtOAc (2 ml) was treated dropwise with ®T3P (propylphosphonic anhydride) (50% w/w in EtOAc) (15.88 g, 24.95 mmol). The resulting mixture was stirred at RT for 16 hrs and diluted with 10% MeOH/EtOAc (62.7 ml). The mixture was washed with 0.5 M LiCl, H2O and sat. NaHCO3. The aqueous layer was back-extracted with 10% MeOH EtOAc (62.7 ml) (3×100 ml). The combined organic extracts was dried MgSO4, filtered and concentrated in vacuo. The resulting solid was triturated with EtOAc and dried at 45° C. to afford the title compound;

Workup

  1. washThe mixture was washed with 0.5 M LiCl, H2O and sat. NaHCO3
  2. extractionThe aqueous layer was back-extracted with 10% MeOH EtOAc (62.7 ml) (3×100 ml)
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo
  5. customThe resulting solid was triturated with EtOAc
  6. customdried at 45° C.

Sources & evidence

ORD record
ord-96bb6dce25bd461a89087e4805f4beb5
Source dataset
uspto-grants-2014_11
Patent number
US08883819B2

Reaction notes

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