N,N-Diethyl-2-propanamine → (S)-1-(3-fluorophenyl)-N-(1-(imidazo[1,2-a]pyrazin-8-yl)pyrrolidin-3-yl)-1H-1,2,4-triazole-3-carboxamide

HRID 1755270Notes

Reaction equation

HRID 1755270 reaction equation
Cl.[N:2]1[CH:3]=[CH:4][N:5]2[CH:10]=[CH:9][N:8]=[C:7]([N:11]3[CH2:15][CH2:14][C@H:13]([NH2:16])[CH2:12]3)[C:6]=12.[F:17][C:18]1[CH:19]=[C:20]([N:24]2[CH:28]=[N:27][C:26]([C:29](O)=[O:30])=[N:25]2)[CH:21]=[CH:22][CH:23]=1.C(N(CC)C(C)C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C.C(OCC)(=O)C>[F:17][C:18]1[CH:19]=[C:20]([N:24]2[CH:28]=[N:27][C:26]([C:29]([NH:16][C@H:13]3[CH2:14][CH2:15][N:11]([C:7]4[C:6]5[N:5]([CH:4]=[CH:3][N:2]=5)[CH:10]=[CH:9][N:8]=4)[CH2:12]3)=[O:30])=[N:25]2)[CH:21]=[CH:22][CH:23]=1

Participants

7

Reactant 4

HCID 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 866882381-(3-fluorophenyl)-1H-1,2,4-triazole-3-carboxylic acidHCID 86720541(5)-1-(Imidazo[1,2-a]pyrazin-8-yl)pyrrolidin-3-amine hydrochloride salt

Product 1

HCID 75202691(S)-1-(3-fluorophenyl)-N-(1-(imidazo[1,2-a]pyrazin-8-yl)pyrrolidin-3-yl)-1H-1,2,4-triazole-3-carboxamideYield 75%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a suspension of (S)-1-(imidazo[1,2-a]pyrazin-8-yl)pyrrolidin-3-amine hydrochloride salt (84 mg, 0.3 mmol) and 1-(3-fluorophenyl)-1H-1,2,4-triazole-3-carboxylic acid (63 mg, 0.3 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 88 mg of the title compound (75% yield) as a 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-1b7506809213495d8c48cf13ee41a72c
Source dataset
uspto-grants-2015_10
Patent number
US09169261B2

Reaction notes

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