Phenyl 5-cyanopyrazin-2-ylcarbamate → 4-(4-{(S)-1-[tert-Butoxycarbonyl-(2-{2-chloro-4-[3-(5-cyano-pyrazin-2-yl)-ureido]-5-methoxy-phenyl}-ethyl)-amino]-ethyl}-phenyl)-piperazine-1-carboxylic acid tert-butyl ester

HRID 1019777Notes

Reaction equation

HRID 1019777 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]([C@@H:20]([N:22]([CH2:30][CH2:31][C:32]3[CH:37]=[C:36]([O:38][CH3:39])[C:35]([NH2:40])=[CH:34][C:33]=3[Cl:41])[C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])[CH3:21])=[CH:16][CH:15]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[C:42]([C:44]1[N:45]=[CH:46][C:47]([NH:50][C:51](=O)[O:52]C2C=CC=CC=2)=[N:48][CH:49]=1)#[N:43]>CN(C=O)C.O>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([C:14]2[CH:19]=[CH:18][C:17]([C@@H:20]([N:22]([C:23]([O:25][C:26]([CH3:28])([CH3:29])[CH3:27])=[O:24])[CH2:30][CH2:31][C:32]3[CH:37]=[C:36]([O:38][CH3:39])[C:35]([NH:40][C:51]([NH:50][C:47]4[CH:46]=[N:45][C:44]([C:42]#[N:43])=[CH:49][N:48]=4)=[O:52])=[CH:34][C:33]=3[Cl:41])[CH3:21])=[CH:16][CH:15]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:2])([CH3:3])[CH3:4]

Participants

5

Reactant 2

HCID 22064357Phenyl 5-cyanopyrazin-2-ylcarbamateHCID 674689714-[4-((S)-1-{[2-(4-amino-2-chloro-5-methoxy-phenyl)-ethyl]-tert-butoxycarbonyl-amino}ethyl)-phenyl]piperazine-1-carboxylic acid tert-butyl ester

Product 1

HCID 674691764-(4-{(S)-1-[tert-Butoxycarbonyl-(2-{2-chloro-4-[3-(5-cyano-pyrazin-2-yl)-ureido]-5-methoxy-phenyl}-ethyl)-amino]-ethyl}-phenyl)-piperazine-1-carboxylic acid tert-butyl esterYield 57.3%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

A stirred solution of 4-[4-((S)-1-{[2-(4-amino-2-chloro-5-methoxy-phenyl)-ethyl]-tert-butoxycarbonyl-amino}ethyl)-phenyl]piperazine-1-carboxylic acid tert-butyl ester (0.28 g, 0.475 mmol) and phenyl 5-cyanopyrazin-2-ylcarbamate (0.091 g, 0.38 mmol) in DMF (18 mL) was heated to 100° C. for 1 hour. The mixture was allowed to cool to room temperature, diluted with water (50 mL) and extracted with EtOAc (2×40 mL). The combined organic extracts were washed with water (3×40 mL), brine (40 mL), dried (Na2SO4) and concentrated under reduced pressure. The residue was purified with column chromatography on neutral silica gel using 25% EtOAc in hexane to give the title compound (0.16 g, 46%).

Workup

  1. extractionextracted with EtOAc (2×40 mL)
  2. washThe combined organic extracts were washed with water (3×40 mL), brine (40 mL)
  3. dry with materialdried (Na2SO4)
  4. concentrationconcentrated under reduced pressure
  5. customThe residue was purified with column chromatography on neutral silica gel using 25% EtOAc in hexane

Sources & evidence

ORD record
ord-8a7d2d904dba4820b371a81bc58dc478
Source dataset
uspto-grants-2014_05
Patent number
US08716287B2

Reaction notes

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