Sulfuric Acid → N2-(4-(4-chloro-1H-imidazol-1-yl)-3-methoxyphenyl)-N4-cyclobutyl-7-phenyl-6,7-dihydro-5H-cyclopenta[d]pyrimidine-2,4-diamine

HRID 451154Notes

Reaction equation

HRID 451154 reaction equation
Cl[C:2]1[N:3]=[C:4]([NH:17][CH:18]2[CH2:21][CH2:20][CH2:19]2)[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:22][C:23]1[N:24]=[CH:25][N:26]([C:28]2[CH:34]=[CH:33][C:31]([NH2:32])=[CH:30][C:29]=2[O:35][CH3:36])[CH:27]=1.OS(O)(=O)=O.CCOC(C)=O>CN1C(=O)CCC1>[Cl:22][C:23]1[N:24]=[CH:25][N:26]([C:28]2[CH:34]=[CH:33][C:31]([NH:32][C:2]3[N:3]=[C:4]([NH:17][CH:18]4[CH2:19][CH2:20][CH2:21]4)[C:5]4[CH2:10][CH2:9][CH:8]([C:11]5[CH:12]=[CH:13][CH:14]=[CH:15][CH:16]=5)[C:6]=4[N:7]=3)=[CH:30][C:29]=2[O:35][CH3:36])[CH:27]=1

Participants

6

Reactant 4

HCID 1118Sulfuric AcidHCID 8857Ethyl AcetateHCID 580753022-chloro-N-cyclobutyl-7-phenyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-amineHCID 580757574-(4-chloro-1H-imidazol-1-yl)-3-methoxyaniline

Product 1

HCID 50913785N2-(4-(4-chloro-1H-imidazol-1-yl)-3-methoxyphenyl)-N4-cyclobutyl-7-phenyl-6,7-dihydro-5H-cyclopenta[d]pyrimidine-2,4-diamineYield 71.6%

Reagents, catalysts & solvents 1

HCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
97 °C

Procedure

To a mixture of 2-chloro-N-cyclobutyl-7-phenyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-amine (165 mg, 0.55 mmol) and 4-(4-chloro-1H-imidazol-1-yl)-3-methoxyaniline (135 mg, 0.605 mmol) in NMP (2 mL) was added Conc. H2SO4 (0.041 mL, 0.771 mmol). The mixture was stirred at 97° C. for 20 hours. After cooled down to room temperature, 100 mL of EtOAc was added, washed with saturated NaHCO3/water and water, dried over Na2SO4, and finally removed. The residue was purified via Biotage (12 g, hexanes-80% EtOAc) to give N2-(4-(4-chloro-1H-imidazol-1-yl)-3-methoxyphenyl)-N4-cyclobutyl-7-phenyl-6,7-dihydro-5H-cyclopenta[d]pyrimidine-2,4-diamine (202 mg, 0.394 mmol, 71.6% yield). LC-MS (M+H)+=487.14. 1H NMR (500 MHz, CDCl3) δ ppm 7.92 (1H, d, J=1.8 Hz), 7.51 (1H, d, J=1.2 Hz), 7.28-7.33 (2H, m), 7.18-7.24 (3H, m), 7.13 (1H, s), 7.03 (1H, d, J=8.5 Hz), 7.01 (1H, d, J=1.2 Hz), 6.74 (1H, dd, J=8.5, 2.1 Hz), 4.64-4.80 (2H, m), 4.17-4.23 (1H, m), 3.49 (3H, s), 2.72-2.81 (1H, m), 2.61-2.71 (2H, m), 2.43-2.53 (2H, m), 2.09 (1H, td, J=8.0, 2.3 Hz), 1.92-2.04 (2H, m), 1.70-1.88 (2H, m).

Workup

  1. temperatureAfter cooled down to room temperature
  2. washwashed with saturated NaHCO3/water and water
  3. dry with materialdried over Na2SO4
  4. customfinally removed
  5. customThe residue was purified via Biotage (12 g, hexanes-80% EtOAc)

Sources & evidence

ORD record
ord-b83a888fca074797b066bbb1bbe21afe
Source dataset
uspto-grants-2013_07
Patent number
US08486952B2

Reaction notes

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