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

HRID 475878Notes

Reaction equation

HRID 475878 reaction equation
Cl[C:2]1[N:3]=[C:4]([NH:17][CH3:18])[C:5]2[CH2:10][CH2:9][CH:8]([C:11]3[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=3)[C:6]=2[N:7]=1.[Cl:19][C:20]1[N:21]=[CH:22][N:23]([C:25]2[CH:31]=[CH:30][C:28]([NH2:29])=[CH:27][C:26]=2[O:32][CH3:33])[CH:24]=1>C1COCC1.C(O)(=O)C>[Cl:19][C:20]1[N:21]=[CH:22][N:23]([C:25]2[CH:31]=[CH:30][C:28]([NH:29][C:2]3[N:3]=[C:4]([NH:17][CH3:18])[C:5]4[CH2:10][CH2:9][CH:8]([C:11]5[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=5)[C:6]=4[N:7]=3)=[CH:27][C:26]=2[O:32][CH3:33])[CH:24]=1

Participants

5

Reactant 2

HCID 580752952-chloro-N-methyl-7-phenyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-amineHCID 580757574-(4-chloro-1H-imidazol-1-yl)-3-methoxyaniline

Product 1

HCID 50913637N2-(4-(4-chloro-1H-imidazol-1-yl)-3-methoxyphenyl)-N4-methyl-7-phenyl-6,7-dihydro-5H-cyclopenta[d]pyrimidine-2,4-diamine

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 8028TetrahydrofuranSolvent

Procedure

A solution of 2-chloro-N-methyl-7-phenyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-amine (833 mg, 3.21 mmol) and 4-(4-chloro-1H-imidazol-1-yl)-3-methoxyaniline (717.9 mg, 3.21 μmol) in THF (5.6 mL) and acetic acid (5.6 mL) was heated at 85° C. in a 350 mL high-pressure vessel overnight. The solvent was removed in vacuum and the residue was dissolved in dichloromethane and washed with saturated aqueous sodium bicarbonate solution. The organic phase was separated and the aqueous phase was extracted with dichloromethane. The combined organic extracts were dried over anhydrous magnesium sulfate and filtered. The solvent was removed in vacuum and the residue was purified by column chromatography on silica gel to give N2-(4-(4-chloro-1H-imidazol-1-yl)-3-methoxyphenyl)-N4-methyl-7-phenyl-6,7-dihydro-5H-cyclopenta[d]pyrimidine-2,4-diamine, which was contaminated with 4-(4-chloro-1H-imidazol-1-yl)-3-methoxyaniline. The material was triturated with methanol, cooled in the freezer and filtered. The residue was washed with freezing cold methanol and dried to give pure N2-(4-(4-chloro-1H-imidazol-1-yl)-3-methoxyphenyl)-N4-methyl-7-phenyl-6,7-dihydro-5H-cyclopenta[d]pyrimidine-2,4-diamine (673.5 mg, 47%) as light brown solid. LC-MS (M+H)+=446.9. 1H NMR (500 MHz, CDCl3) δ ppm 7.99 (1H, d, J=1.8 Hz), 7.48 (1H, s), 7.27-7.33 (2H, m), 7.16-7.24 (3H, m), 6.96-7.07 (3H, m), 6.71 (1H, dd, J=8.4, 1.7 Hz), 4.50 (1H, br s), 4.20 (1H, s), 3.48 (3H, s), 3.11 (3H, d, J=4.9 Hz), 2.59-2.79 (3H, m), 2.01-2.13 (1H, m).

Workup

  1. customThe solvent was removed in vacuum
  2. dissolutionthe residue was dissolved in dichloromethane
  3. washwashed with saturated aqueous sodium bicarbonate solution
  4. customThe organic phase was separated
  5. extractionthe aqueous phase was extracted with dichloromethane
  6. dry with materialThe combined organic extracts were dried over anhydrous magnesium sulfate
  7. filtrationfiltered
  8. customThe solvent was removed in vacuum
  9. customthe residue was purified by column chromatography on silica gel

Sources & evidence

ORD record
ord-bf25643ac2a1451d93c2bc43ac801bab
Source dataset
uspto-grants-2014_01
Patent number
US08637525B2

Reaction notes

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