4-(4-chloro-1H-imidazol-1-yl)-3-methoxyaniline → N2-(4-(4-chloro-1H-imidazol-1-yl)-3-methoxyphenyl)-7-(4-fluorophenyl)-N4-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidine-2,4-diamine

HRID 451156

Reaction equation

HRID 451156 reaction equation
Cl[C:2]1[N:3]=[C:4]([NH:18][CH3:19])[C:5]2[CH2:10][CH2:9][CH:8]([C:11]3[CH:16]=[CH:15][C:14]([F:17])=[CH:13][CH:12]=3)[C:6]=2[N:7]=1.[Cl:20][C:21]1[N:22]=[CH:23][N:24]([C:26]2[CH:32]=[CH:31][C:29]([NH2:30])=[CH:28][C:27]=2[O:33][CH3:34])[CH:25]=1>C1COCC1.C(O)(=O)C>[Cl:20][C:21]1[N:22]=[CH:23][N:24]([C:26]2[CH:32]=[CH:31][C:29]([NH:30][C:2]3[N:3]=[C:4]([NH:18][CH3:19])[C:5]4[CH2:10][CH2:9][CH:8]([C:11]5[CH:16]=[CH:15][C:14]([F:17])=[CH:13][CH:12]=5)[C:6]=4[N:7]=3)=[CH:28][C:27]=2[O:33][CH3:34])[CH:25]=1

Participants

5

Reactant 2

HCID 580757574-(4-chloro-1H-imidazol-1-yl)-3-methoxyanilineHCID 580758122-chloro-7-(4-fluorophenyl)-N-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-amine

Product 1

HCID 50913787N2-(4-(4-chloro-1H-imidazol-1-yl)-3-methoxyphenyl)-7-(4-fluorophenyl)-N4-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidine-2,4-diamineYield 40.4%

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 8028TetrahydrofuranSolvent

Procedure

A solution of 2-chloro-7-(4-fluorophenyl)-N-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-amine (307.5 mg, 1.107 mmol) and 4-(4-chloro-1H-imidazol-1-yl)-3-methoxyaniline (248 mg, 1.107 mmol) in THF (3 mL) and acetic acid (3.00 mL) was heated at 80° C. overnight. The solvent was removed in vacuum and the residue was triturated with methanol, cooled in the freezer and filtered. The precipitate was thoroughly washed with methanol and dried to give N2-(4-(4-chloro-1H-imidazol-1-yl)-3-methoxyphenyl)-7-(4-fluorophenyl)-N4-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidine-2,4-diamine (207.9 mg, 0.447 mmol, 40.4% yield) as off-white solid. LC-MS (M+H)+=465.0. 1H NMR (500 MHz, CDCl3) δ ppm 9.18 (1H, s), 8.15 (1H, d, J=1.8 Hz), 7.73 (1H, d, J=1.5 Hz), 7.41 (1H, d, J=1.5 Hz), 7.18-7.26 (2H, m), 7.07-7.18 (2H, m), 6.88-7.00 (1H, m), 4.12-4.20 (1H, m), 4.04-4.12 (1H, br s), 3.60 (3H, s), 3.17 (1H, s), 2.96 (3H, d, J=4.6 Hz), 2.71-2.81 (1H, m), 2.52-2.66 (2H, m), 1.83-1.96 (1H, m).

Workup

  1. customThe solvent was removed in vacuum
  2. customthe residue was triturated with methanol
  3. temperaturecooled in the freezer
  4. filtrationfiltered
  5. washThe precipitate was thoroughly washed with methanol
  6. customdried

Sources & evidence

ORD record
ord-3466279d65b34aaebfbd6f590840aea3
Source dataset
uspto-grants-2013_07
Patent number
US08486952B2

Linked notes

Loading…