Triethylamine → 3-(2-Fluorophenyl)-5-{4-[2-(pyrrolidin-1-yl)ethyl]piperazin-1-yl}-[1,2,3]triazolo[1,5-a]quinazoline

HRID 1581636Notes

Reaction equation

HRID 1581636 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[N:9]=[N:10][N:11]2[C:20]3[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=3)[C:14]([N:21]3[CH2:26][CH2:25][NH:24][CH2:23][CH2:22]3)=[N:13][C:12]=12.Cl.Cl[CH2:29][CH2:30][N:31]1[CH2:35][CH2:34][CH2:33][CH2:32]1.C(N(CC)CC)C>CN(C)C=O.O>[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[N:9]=[N:10][N:11]2[C:20]3[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=3)[C:14]([N:21]3[CH2:22][CH2:23][N:24]([CH2:29][CH2:30][N:31]4[CH2:35][CH2:34][CH2:33][CH2:32]4)[CH2:25][CH2:26]3)=[N:13][C:12]=12

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 816681-(2-Chloroethyl)pyrrolidine hydrochlorideHCID 700325103-(2-Fluorophenyl)-5-(piperazin-1-yl)-[1,2,3]triazolo[1,5-a]quinazoline

Product 1

HCID 102973393-(2-Fluorophenyl)-5-{4-[2-(pyrrolidin-1-yl)ethyl]piperazin-1-yl}-[1,2,3]triazolo[1,5-a]quinazolineYield 47.5%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

3-(2-Fluorophenyl)-5-(piperazin-1-yl)-[1,2,3]triazolo[1,5-α]quinazoline (0.10 g, 0.26 mmol), 1-(2-chloroethyl)pyrrolidine hydrochloride (0.088 g, 0.52 mmol) and triethylamine (0.18 ml, 1.3 mmol) were dissolved in N,N-dimethylformamide (4 ml) and stirred at 80° C. under nitrogen for 18 h. The mixture was cooled, then diluted with water (20 ml) and extracted with CH2Cl2 (2×50 ml). The combined organics were washed with brine (20 ml), dried over MgSO4 and evaporated to give a brown oil. Purification by preparative thin layer chromatography eluting with CH2Cl2:MeOH:NH3(c) (92:8:0.8) gave 3-(2-fluorophenyl)-5-{4-[2-(pyrrolidin-1-yl)ethyl]piperazin-1-yl}-[1,2,3]triazolo[1,5-α]quinazoline as a white solid (0.055 g, 47%). Oxalate salt (EtOH): δH (400 MHz; DMSO) 1.87-1.98 (4H, m), 2.49-2.52 (6H, m, partly obscured by DMSO peak), 2.66-2.78 (6H, m), 3.30-3.35 (2H, m, partly obscured by H20 peak), 3.60-3.72 (2H, m), 7.33-7.39 (2H, m), 7.43-7.49 (1H, m), 7.77 (1H, ddd, J=8, 8 and 1), 8.05-8.13 (2H, m), 8.19 (1H, d, J=8), 8.59 (1H, dd, J=8 and 1); m/z (ES+) 446 (M+H+).

Workup

  1. temperatureThe mixture was cooled
  2. extractionextracted with CH2Cl2 (2×50 ml)
  3. washThe combined organics were washed with brine (20 ml)
  4. dry with materialdried over MgSO4
  5. customevaporated
  6. customto give a brown oil
  7. customPurification by preparative thin layer chromatography
  8. washeluting with CH2Cl2:MeOH:NH3(c) (92:8:0.8)

Sources & evidence

ORD record
ord-67df2380ef314029971c2e062595c292
Source dataset
uspto-grants-2004_05
Patent number
US06730681B2

Reaction notes

Loading…