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

HRID 1755262Notes

Reaction equation

HRID 1755262 reaction equation
Cl.[N:2]1[N: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:23]=[CH:22][C:21]([N:24]2[CH:28]=[N:27][C:26]([C:29](O)=[O:30])=[N:25]2)=[CH:20][CH:19]=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>[N:2]1[N:3]=[CH:4][N:5]2[CH:10]=[CH:9][N:8]=[C:7]([N:11]3[CH2:15][CH2:14][C@H:13]([NH:16][C:29]([C:26]4[N:27]=[CH:28][N:24]([C:21]5[CH:22]=[CH:23][C:18]([F:17])=[CH:19][CH:20]=5)[N:25]=4)=[O:30])[CH2:12]3)[C:6]=12

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 838201611-(4-Fluorophenyl)-1,2,4-triazole-3-carboxylic acidHCID 86720539(S)-1-([1,2,4]triazolo[4,3-a]pyrazin-8-yl)pyrrolidin-3-amine hydrochloride salt

Product 1

HCID 86720540(S)-N-(1-([1,2,4]triazolo[4,3-a]pyrazin-8-yl)pyrrolidin-3-yl)-1-(4-fluorophenyl)-1H-1,2,4-triazole-3-carboxamideYield 40.7%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a suspension of (S)-1-([1,2,4]triazolo[4,3-a]pyrazin-8-yl)pyrrolidin-3-amine hydrochloride salt (63 mg, 0.23 mmol), 1-(4-fluorophenyl)-1H-1,2,4-triazole-3-carboxylic acid (42 mg, 0.2 mmol) in DMF (5 mL) was added diethylisopropyl amine (650 mg, 5 mmol), followed by HATU (76 mg, 0.2 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 32 mg of the title compound (40% 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-c2f8272317b84e3f92f9f2b3b3c9b79b
Source dataset
uspto-grants-2015_10
Patent number
US09169261B2

Reaction notes

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