Phenyl 5-cyanopyrazin-2-ylcarbamate → Tert-butyl 4-(4-((tert-butoxycarbonyl (2-chloro-4-(3-(5-cyanopyrazin-2-yl) ureido)-5-methoxy-phenethyl)amino)methyl)phenyl)piperazine-1-carboxylate

HRID 1019781Notes

Reaction equation

HRID 1019781 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([C:14]2[CH:19]=[CH:18][C:17]([CH2:20][N:21]([CH2:29][CH2:30][C:31]3[CH:36]=[C:35]([O:37][CH3:38])[C:34]([NH2:39])=[CH:33][C:32]=3[Cl:40])[C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])=[CH:16][CH:15]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[C:41]([C:43]1[N:44]=[CH:45][C:46]([NH:49][C:50](=O)[O:51]C2C=CC=CC=2)=[N:47][CH:48]=1)#[N:42]>CN(C=O)C.O>[C:25]([O:24][C:22]([N:21]([CH2:20][C:17]1[CH:18]=[CH:19][C:14]([N:11]2[CH2:12][CH2:13][N:8]([C:6]([O:5][C:1]([CH3:2])([CH3:3])[CH3:4])=[O:7])[CH2:9][CH2:10]2)=[CH:15][CH:16]=1)[CH2:29][CH2:30][C:31]1[CH:36]=[C:35]([O:37][CH3:38])[C:34]([NH:39][C:50]([NH:49][C:46]2[CH:45]=[N:44][C:43]([C:41]#[N:42])=[CH:48][N:47]=2)=[O:51])=[CH:33][C:32]=1[Cl:40])=[O:23])([CH3:26])([CH3:28])[CH3:27]

Participants

5

Reactant 2

HCID 22064357Phenyl 5-cyanopyrazin-2-ylcarbamateHCID 67465937Tert-butyl-4-(4-(((4-amino-2-chloro-5-methoxyphenethyl)(tert-butoxycarbonyl)amino)methyl)phenyl)piperazine-1-carboxylate

Product 1

HCID 67465989Tert-butyl 4-(4-((tert-butoxycarbonyl (2-chloro-4-(3-(5-cyanopyrazin-2-yl) ureido)-5-methoxy-phenethyl)amino)methyl)phenyl)piperazine-1-carboxylateYield 54.2%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

A stirred solution of tert-butyl-4-(4-(((4-amino-2-chloro-5-methoxyphenethyl)(tert-butoxycarbonyl)amino)methyl)phenyl)piperazine-1-carboxylate (0.46 g, 0.800 mmol) and phenyl 5-cyanopyrazin-2-ylcarbamate (0.153 g, 0.64 mmol) in DMF (18 mL) was heated to 100° C. for 1.5 hours. The mixture was allowed to cool to room temperature, diluted with water (40 mL) and extracted with EtOAc (2×30 mL). The combined organic extracts were washed with water (3×15 mL), brine (10 mL), dried (Na2SO4) and concentrated under reduced pressure. The residue was purified with column chromatography on neutral silica gel using 1.5% methanol in DCM to give the title compound (0.25 g, 43%).

Workup

  1. extractionextracted with EtOAc (2×30 mL)
  2. washThe combined organic extracts were washed with water (3×15 mL), brine (10 mL)
  3. dry with materialdried (Na2SO4)
  4. concentrationconcentrated under reduced pressure
  5. customThe residue was purified with column chromatography on neutral silica gel using 1.5% methanol in DCM

Sources & evidence

ORD record
ord-e1e45a53c6d1456bb2befa121013f5bf
Source dataset
uspto-grants-2014_05
Patent number
US08716287B2

Reaction notes

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