Dimethylformamide → (S)-1-(4-chlorophenyl)-N-(1-(pyrrolo[1,2-a]pyrazin-1-yl)pyrrolidin-3-yl)-1H-1,2,4-triazole-3-carboxamide

HRID 1755272Notes

Reaction equation

HRID 1755272 reaction equation
C1(C2O[N:10]=[C:9]([C:12]([OH:14])=O)[N:8]=2)C=CC=CC=1.[ClH:15].N1C=N[N:19]2[C:24]([N:25]3[CH2:29][CH2:28][C@H:27]([NH2:30])[CH2:26]3)=[CH:23][N:22]=[CH:21][C:20]=12.C(N(CC)[CH:34]([CH3:36])[CH3:35])C.CN(C(ON1N=N[C:49]2[CH:50]=[CH:51][CH:52]=N[C:48]1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C[N:64]([CH:66]=O)[CH3:65]>C(OCC)(=O)C>[Cl:15][C:50]1[CH:51]=[CH:52][C:65]([N:64]2[CH:66]=[N:8][C:9]([C:12]([NH:30][C@H:27]3[CH2:28][CH2:29][N:25]([C:24]4[C:23]5[N:22]([CH:36]=[CH:34][CH:35]=5)[CH:21]=[CH:20][N:19]=4)[CH2:26]3)=[O:14])=[N:10]2)=[CH:48][CH:49]=1

Participants

7

Reactant 5

HCID 6228DimethylformamideHCID 521913N,N-Diethyl-2-propanamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 218070875-Phenyl-1,2,4-oxadiazole-3-carboxylic acidHCID 86720545(S)-1-([1,2,4]triazolo[1,5-a]pyrazin-5-yl)pyrrolidin-3-amine hydrochloride salt

Product 1

HCID 75202693(S)-1-(4-chlorophenyl)-N-(1-(pyrrolo[1,2-a]pyrazin-1-yl)pyrrolidin-3-yl)-1H-1,2,4-triazole-3-carboxamideYield 23%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

To a suspension of the above 5-phenyl-1,2,4-oxadiazole-3-carboxylic acid (58 mg, 0.3 mmol), (S)-1-([1,2,4]triazolo[1,5-a]pyrazin-5-yl)pyrrolidin-3-amine hydrochloride salt (90 mg, 0.32 mmol) in DMF (5 mL) was added diethylisopropyl amine (650 mg, 5 mmol), followed by HATU (120 mg, 0.31 mmol). The resulting solution was stirred at room temperature for 1 h. The reaction mixture was diluted with ethyl acetate and washed with saturated aqueous solutions of KH2PO4 and NaHCO3, followed by brine. The organic layer was concentrated in vacuo and the residue purified by reverse phase HPLC (acetonitrile-H2O with 0.1% TFA as eluent) to give 26 mg of the title compound (23% yield) as white solid.

Workup

  1. washwashed with saturated aqueous solutions of KH2PO4 and NaHCO3
  2. concentrationThe organic layer was concentrated in vacuo
  3. customthe residue purified by reverse phase HPLC (acetonitrile-H2O with 0.1% TFA as eluent)

Sources & evidence

ORD record
ord-4b6c9babee384915b712dd58e86abc2a
Source dataset
uspto-grants-2015_10
Patent number
US09169261B2

Reaction notes

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