1,8-Diazabicyclo(5.4.0)undec-7-ene → 3-[(7-fluoroimidazo[1,2-a]quinoxalin-4-yl)amino]propyl (2R)-2-[(tert-butoxycarbonyl)amino]propanoate

HRID 1893494Notes

Reaction equation

HRID 1893494 reaction equation
[F:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]1[CH:12]=[CH:13][N:14]=[C:7]1[C:6]([NH:15][CH2:16][CH2:17][CH2:18][OH:19])=[N:5]2.N12CCCN=C1CCCCC2.O=C1CCC(=O)N1[O:38][C:39](=O)[C@H:40]([NH:42][C:43](=[O:49])[O:44][C:45]([CH3:48])([CH3:47])[CH3:46])[CH3:41]>CN(C)C=O.O>[C:45]([O:44][C:43]([NH:42][C@H:40]([CH3:41])[C:39]([O:19][CH2:18][CH2:17][CH2:16][NH:15][C:6]1[C:7]2[N:8]([CH:12]=[CH:13][N:14]=2)[C:9]2[C:4]([N:5]=1)=[CH:3][C:2]([F:1])=[CH:11][CH:10]=2)=[O:38])=[O:49])([CH3:48])([CH3:47])[CH3:46]

Participants

6

Reactant 3

HCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 43293623-[(7-Fluoroimidazo[1,2-a]quinoxalin-4-yl)amino]propan-1-olHCID 11580086N-[(1,1-Dimethylethoxy)carbonyl]-D-alanine 2,5-dioxo-1-pyrrolidinyl ester

Product 1

HCID 593333143-[(7-fluoroimidazo[1,2-a]quinoxalin-4-yl)amino]propyl (2R)-2-[(tert-butoxycarbonyl)amino]propanoateYield 12%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent2×

Conditions

Temperature
60 °C

Procedure

To a solution of commercially available (Peakdale) 3-[(7-fluoroimidazo[1,2-a]quinoxalin-4-yl)amino]propan-1-ol (20 mg, 0.08 mmol) and 1,8-diazabicyclo[5.4.0]undec-7-ene (12 μL, 0.08 mmol) in anhydrous dimethylformamide (600 μL) under argon was added dropwise a solution of tert-butyl {(1R)-2-[(2,5-dioxopyrrolidin-1-yl)oxy]-1-methyl-2-oxoethyl}carbamate (22 mg, 0.08 mmol) in anhydrous dimethylformamide (200 μL). The mixture was stirred at 60° C. for 65 h, then diluted with cold water and extracted four times with chloroform and once with chloroform/isopropanol (5:1). The combined organic layers were washed with brine, dried over sodium sulfate, filtered and evaporated. The crude product was purified by preparative TLC (silica, dichloromethane/methanol 20/1) to afford the title compound as a colorless oil (4 mg, 12%).

Workup

  1. extractionextracted four times with chloroform
  2. washThe combined organic layers were washed with brine
  3. dry with materialdried over sodium sulfate
  4. filtrationfiltered
  5. customevaporated
  6. customThe crude product was purified by preparative TLC (silica, dichloromethane/methanol 20/1)

Sources & evidence

ORD record
ord-84aa437415f64c03aef66361a8453af1
Source dataset
uspto-grants-2013_08
Patent number
US08513250B2

Reaction notes

Loading…