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

HRID 1755264Notes

Reaction equation

HRID 1755264 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]=[C:26]([C:28](O)=[O:29])[N:25]=[CH: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:26]4[N:25]=[CH:24][N:23]([C:17]5[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=5)[CH:27]=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 234450471-Phenyl-1H-imidazole-4-carboxylic acidHCID 86720539(S)-1-([1,2,4]triazolo[4,3-a]pyrazin-8-yl)pyrrolidin-3-amine hydrochloride salt

Product 1

HCID 75202556(S)-N-(1-([1,2,4]triazolo[4,3-a]pyrazin-8-yl)pyrrolidin-3-yl)-1-phenyl-1H-imidazole-4-carboxamideYield 67%

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 (109 mg, 0.4 mmol) and 1-phenyl-1H-imidazole-4-carboxylic acid (76 mg, 04 mmol) in DMF (5 mL) was added diethylisopropyl amine (650 mg, 5 mmol), followed by HATU (160 mg, 0.41 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 100 mg of the title compound (67% yield) as a white solid. MS: (ES) m/z found 375.1.

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-648e477903a745b3b7515e6bf3421fc0
Source dataset
uspto-grants-2015_10
Patent number
US09169261B2

Reaction notes

Loading…