Water → ethyl 6-(4-{5-[3-({[N-(tert-butoxycarbonyl)glycyl](methyl)amino}methyl)phenyl]pyrimidin-2-yl}piperazin-1-yl)nicotinate

HRID 2403577Notes

Reaction equation

HRID 2403577 reaction equation
[CH3:1][N:2]([CH2:14][C:15]1[CH:20]=[CH:19][CH:18]=[C:17]([C:21]2[CH:22]=[N:23][C:24]([N:27]3[CH2:32][CH2:31][NH:30][CH2:29][CH2:28]3)=[N:25][CH:26]=2)[CH:16]=1)[C:3](=[O:13])[CH2:4][NH:5][C:6](=[O:12])[O:7][C:8]([CH3:11])([CH3:10])[CH3:9].Cl[C:34]1[CH:44]=[CH:43][C:37]([C:38]([O:40][CH2:41][CH3:42])=[O:39])=[CH:36][N:35]=1.C(N(CCCC)CCCC)CCC.O>CN1C(=O)CCC1>[C:8]([O:7][C:6]([NH:5][CH2:4][C:3]([N:2]([CH2:14][C:15]1[CH:16]=[C:17]([C:21]2[CH:22]=[N:23][C:24]([N:27]3[CH2:32][CH2:31][N:30]([C:34]4[CH:44]=[CH:43][C:37]([C:38]([O:40][CH2:41][CH3:42])=[O:39])=[CH:36][N:35]=4)[CH2:29][CH2:28]3)=[N:25][CH:26]=2)[CH:18]=[CH:19][CH:20]=1)[CH3:1])=[O:13])=[O:12])([CH3:11])([CH3:9])[CH3:10]

Participants

6

Reactant 4

HCID 962WaterHCID 7622TributylamineHCID 2799611Ethyl 6-chloronicotinateHCID 70570767HCID 70570767, compound

Product 1

HCID 68106649ethyl 6-(4-{5-[3-({[N-(tert-butoxycarbonyl)glycyl](methyl)amino}methyl)phenyl]pyrimidin-2-yl}piperazin-1-yl)nicotinateYield 37.4%

Reagents, catalysts & solvents 1

HCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
100 °C

Procedure

tert-Butyl (2-{methyl[3-(2-piperazin-1-ylpyrimidin-5-yl)benzyl]amino}-2-oxoethyl)carbamate (200 mg) and ethyl 6-chloronicotinate (169 mg) were dissolved in NMP (4 ml), and N,N-dibutylbutan-1-amine (252 mg) was added thereto, followed by stirring at 100° C. overnight. To the reaction mixture was added water, followed by extraction with EtOAc. The organic layer was washed with saturated brine and dried over MgSO4, and then the solvent was evaporated under reduced pressure. The obtained residue was purified by silica gel column chromatography (0% to 8% CHCl3/MeOH) to obtain ethyl 6-(4-{5-[3-({[N-(tert-butoxycarbonyl)glycyl](methyl)amino}methyl)phenyl]pyrimidin-2-yl}piperazin-1-yl)nicotinate (100 mg).

Workup

  1. extractionfollowed by extraction with EtOAc
  2. washThe organic layer was washed with saturated brine
  3. dry with materialdried over MgSO4
  4. customthe solvent was evaporated under reduced pressure
  5. customThe obtained residue was purified by silica gel column chromatography (0% to 8% CHCl3/MeOH)

Sources & evidence

ORD record
ord-a31082a9ebd74b10b9e6eed1a5233123
Source dataset
uspto-grants-2014_08
Patent number
US08802679B2

Reaction notes

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