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

HRID 1755261Notes

Reaction equation

HRID 1755261 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.[C:17]1([N:23]2[CH:27]=[N:26][C:25]([C:28](O)=[O:29])=[N:24]2)[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=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:28]([C:25]4[N:26]=[CH:27][N:23]([C:17]5[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=5)[N:24]=4)=[O:29])[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 123160561-Phenyl-1H-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 75202554(S)-N-(1-([1,2,4]triazolo[4,3-a]pyrazin-8-yl)pyrrolidin-3-yl)-1-phenyl-1H-1,2,4-triazole-3-carboxamideYield 20.4%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a suspension of the above (S)-1-([1,2,4]triazolo[4,3-a]pyrazin-8-yl)pyrrolidin-3-amine hydrochloride salt (90 mg, 0.32 mmol), 1-phenyl-1H-1,2,4-triazole-3-carboxylic acid (58 mg, 0.30 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 23 mg of the title compound (20% yield) as white solid. 1H NMR (400 MHz, d6-DMSO) δ 2.10-2.38 (two sets of m, 2 H), 3.50-4.60 (br, 4 H), 4.65 (m, 1 H), 7.29 (d, J=4.4 Hz, 1 H), 7.46 (t, J=7.3 Hz, 1 H), 7.59 (t, J=7.3 Hz, 2 H), 7.75 (d, J=4.7 Hz, 1 H), 7.90 (d, J=8.0 Hz, 2 H), 9.00 (d, J=7.0H, 1 H), 9.20 (s, 1 H), 9.40 (s, 1 H). MS: (ES) m/z calculated for C18H17N9O [M+H]+ 376.2, found 376.2.

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-a51a2c2f4e7446619a772f72df316df5
Source dataset
uspto-grants-2015_10
Patent number
US09169261B2

Reaction notes

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