[2-[2-[1-[[4-[5-[(Ethylamino)carbonyl]-2-methylphenyl]-3,4-dihydro-3-oxopyrazinyl]amino]-1-methylethyl]phenoxy]ethyl]methyl-carbamic acid phenylmethyl ester → N-Ethyl-4-methyl-3-[3-[[1-methyl-1-[2-[2-(methylamino)ethoxy]phenyl]ethyl]amino]-2-oxo-1(2H)-pyrazinyl]-benzamide

HRID 1697337Notes

Reaction equation

HRID 1697337 reaction equation
C1(CO[C:9](=O)[N:10]([CH2:12][CH2:13][O:14][C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=2[C:21]([NH:24][C:25]2[C:30](=[O:31])[N:29]([C:32]3[CH:37]=[C:36]([C:38]([NH:40][CH2:41][CH3:42])=[O:39])[CH:35]=[CH:34][C:33]=3[CH3:43])[CH:28]=[CH:27][N:26]=2)([CH3:23])[CH3:22])C)C=CC=CC=1>[Pd].C(O)C>[CH2:41]([NH:40][C:38](=[O:39])[C:36]1[CH:35]=[CH:34][C:33]([CH3:43])=[C:32]([N:29]2[CH:28]=[CH:27][N:26]=[C:25]([NH:24][C:21]([CH3:22])([C:16]3[CH:17]=[CH:18][CH:19]=[CH:20][C:15]=3[O:14][CH2:13][CH2:12][NH:10][CH3:9])[CH3:23])[C:30]2=[O:31])[CH:37]=1)[CH3:42]

Participants

4

Reactant 1

HCID 66689896[2-[2-[1-[[4-[5-[(Ethylamino)carbonyl]-2-methylphenyl]-3,4-dihydro-3-oxopyrazinyl]amino]-1-methylethyl]phenoxy]ethyl]methyl-carbamic acid phenylmethyl ester

Product 1

HCID 66690353N-Ethyl-4-methyl-3-[3-[[1-methyl-1-[2-[2-(methylamino)ethoxy]phenyl]ethyl]amino]-2-oxo-1(2H)-pyrazinyl]-benzamideYield 0.2%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 702EthanolSolvent

Procedure

To [2-[2-[1-[[4-[5-[(ethylamino)carbonyl]-2-methylphenyl]-3,4-dihydro-3-oxopyrazinyl]amino]-1-methylethyl]phenoxy]ethyl]methyl-carbamic acid phenylmethyl ester (Example 220d, 1.10 g) was added ethanol (10 mL) and this was pumped through a Pd/C cartridge at 1 mL/min under max H2 at 50° C. on an H-Cube hydrogenator. The solvents were removed in vacuo and the residue then taken up in acetonitrile. Purification by preparative HPLC (ACE column, 0.2% TFA:acetonitrile eluent) followed by treatment with SCX resin (eluting with methanol (discarded) followed by 7N NH3 in methanol and collected the basic fractions) and trituration with diethyl ether afforded the title product (2 mg).

Workup

  1. customThe solvents were removed in vacuo
  2. customPurification by preparative HPLC (ACE column, 0.2% TFA:acetonitrile eluent)
  3. washeluting with methanol (discarded)
  4. customcollected the basic fractions) and trituration with diethyl ether

Sources & evidence

ORD record
ord-568725e1f91640d2bf3499a16b966fe2
Source dataset
uspto-grants-2012_04
Patent number
US08163905B2

Reaction notes

Loading…