(4-Amino-3-methoxy-benzyl)-benzyl-carbamic acid tert-butyl ester → Benzyl-{4-[3-(5-cyano-pyrazin-2-yl)-ureido]-3-methoxy-benzyl}-carbamic acid tert-butyl ester

HRID 1019754Notes

Reaction equation

HRID 1019754 reaction equation
[C:1]([O:5][C:6](=[O:25])[N:7]([CH2:15][C:16]1[CH:21]=[CH:20][C:19]([NH2:22])=[C:18]([O:23][CH3:24])[CH:17]=1)[CH2:8][C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1)([CH3:4])([CH3:3])[CH3:2].[C:26]([C:28]1[N:29]=[CH:30][C:31]([NH:34][C:35](=O)[O:36]C2C=CC=CC=2)=[N:32][CH:33]=1)#[N:27]>CN(C=O)C>[C:1]([O:5][C:6](=[O:25])[N:7]([CH2:8][C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1)[CH2:15][C:16]1[CH:21]=[CH:20][C:19]([NH:22][C:35]([NH:34][C:31]2[CH:30]=[N:29][C:28]([C:26]#[N:27])=[CH:33][N:32]=2)=[O:36])=[C:18]([O:23][CH3:24])[CH:17]=1)([CH3:4])([CH3:3])[CH3:2]

Participants

4

Reactant 2

HCID 21034184(4-Amino-3-methoxy-benzyl)-benzyl-carbamic acid tert-butyl esterHCID 22064357Phenyl 5-cyanopyrazin-2-ylcarbamate

Product 1

HCID 67469180Benzyl-{4-[3-(5-cyano-pyrazin-2-yl)-ureido]-3-methoxy-benzyl}-carbamic acid tert-butyl esterYield 67.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

(4-Amino-3-methoxy-benzyl)-benzyl-carbamic acid tert-butyl ester (0.25 g, 0.73 mmol) and phenyl 5-cyanopyrazin-2-ylcarbamate (0.21 g 0.87 mmol) (Example 10) were dissolved in DMF (2.5 mL) and heated at 80° C. for 2 hours. The mixture was allowed to cool to room temperature then partitioned between water (15 mL) and EtOAc (25 mL). The separated aqueous layer was extracted with EtOAC (25 ml), and then the combined organic extracts were washed with water (15 mL), brine (10 mL), dried (Na2SO4) and concentrated under reduced pressure. The residue was purified by column chromatography on neutral silica gel using 15-25% EtOAc in hexane to afford the title compound (0.24 g, 67%).

Workup

  1. temperatureto cool to room temperature
  2. customthen partitioned between water (15 mL) and EtOAc (25 mL)
  3. extractionThe separated aqueous layer was extracted with EtOAC (25 ml)
  4. washthe combined organic extracts were washed with water (15 mL), brine (10 mL)
  5. dry with materialdried (Na2SO4)
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was purified by column chromatography on neutral silica gel using 15-25% EtOAc in hexane

Sources & evidence

ORD record
ord-f15812e27e2e479c84682c7fa7e02bc8
Source dataset
uspto-grants-2014_05
Patent number
US08716287B2

Reaction notes

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