{3-[3-(2-cyano-benzyl)-5-methyl-4-oxo-4,5-dihydro-3H-1,3,5,6-tetraaza-cyclopenta[a]naphthalen-2-yl]-cyclohexyl}-carbamic acid benzyl ester → 2-[2-(3-Amino-cyclohexyl)-5-methyl-4-oxo-4,5-dihydro-1,3,5,6-tetraaza-cyclopenta[a]naphthalen-3-ylmethyl]-benzonitrile

HRID 2244815Notes

Reaction equation

HRID 2244815 reaction equation
C(OC(=O)[NH:10][CH:11]1[CH2:16][CH2:15][CH2:14][CH:13]([C:17]2[N:18]([CH2:32][C:33]3[CH:38]=[CH:37][CH:36]=[CH:35][C:34]=3[C:39]#[N:40])[C:19]3[C:28](=[O:29])[N:27]([CH3:30])[C:26]4[C:21](=[CH:22][CH:23]=[CH:24][N:25]=4)[C:20]=3[N:31]=2)[CH2:12]1)C1C=CC=CC=1>[Pd].CCO.C1COCC1>[NH2:10][CH:11]1[CH2:16][CH2:15][CH2:14][CH:13]([C:17]2[N:18]([CH2:32][C:33]3[CH:38]=[CH:37][CH:36]=[CH:35][C:34]=3[C:39]#[N:40])[C:19]3[C:28](=[O:29])[N:27]([CH3:30])[C:26]4[C:21](=[CH:22][CH:23]=[CH:24][N:25]=4)[C:20]=3[N:31]=2)[CH2:12]1

Participants

4

Reactant 1

HCID 16045626{3-[3-(2-cyano-benzyl)-5-methyl-4-oxo-4,5-dihydro-3H-1,3,5,6-tetraaza-cyclopenta[a]naphthalen-2-yl]-cyclohexyl}-carbamic acid benzyl ester

Product 1

HCID 160456862-[2-(3-Amino-cyclohexyl)-5-methyl-4-oxo-4,5-dihydro-1,3,5,6-tetraaza-cyclopenta[a]naphthalen-3-ylmethyl]-benzonitrileYield 72.7%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 21873804Tetrahydrofuran ethanolSolvent

Procedure

A solution of {3-[3-(2-cyano-benzyl)-5-methyl-4-oxo-4,5-dihydro-3H-1,3,5,6-tetraaza-cyclopenta[a]naphthalen-2-yl]-cyclohexyl}-carbamic acid benzyl ester (55 mg, 0.10 mmol) in 1:1 EtOH/THF (8 mL) was hydrogenated at 1 atm over 10% Pd/C (54 mg, 0.05 mmol) at room temperature. After 90 min, the reaction vessel was purged with nitrogen, and the catalyst was removed by filtration, rinsing with MeOH to provide 2-[2-(3-amino-cyclohexyl)-5-methyl-4-oxo-4,5-dihydro-1,3,5,6-tetraaza-cyclopenta[a]naphthalen-3-ylmethyl]-benzonitrile (30 mg, 72% yield). The crude amine was taken up in 2 mL of EtOAc and a minimum amount of EtOH, and was treated with 0.2 mL of 1N HCl in diethyl ether. The solvent was removed to give the corresponding HCl salt as a white solid. 1H-NMR (DMSO): δ 8.65 (m, 1H), 8.53 (dd, 1H, J=7.6, 1.6 Hz), 8.11 (m, 2H), 7.95 (m, 1H), 7.59 (t, 1H, J=7.6 Hz), 7.49 (m, 1H), 7.42 (m, 1H), 6.68 (d, 1H, J=7.6 Hz), 6.04 (m, 2H), 4.61 (m, 1H), 3.70 (s, 3H), 3.17 (m, 1H), 2.18 (m, 1H), 1.97 (m, 2H), 1.82 (m, 1H), 1.71 (m, 2H), 1.51 (m, 1H), 1.41 (m, 1H). MS: calculated for C24H24N6O+H. 413.2; found: 413.3.

Workup

  1. customthe reaction vessel was purged with nitrogen
  2. customthe catalyst was removed by filtration
  3. washrinsing with MeOH

Sources & evidence

ORD record
ord-0d9c88a4049a4a17ab6bdc9f21973af4
Source dataset
uspto-grants-2010_03
Patent number
US07678909B1

Reaction notes

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