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

HRID 475880Notes

Reaction equation

HRID 475880 reaction equation
Cl[C:2]1[N:3]=[C:4]([NH:17][CH:18]2[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:21][C:22]1[N:23]=[CH:24][N:25]([C:27]2[CH:33]=[CH:32][C:30]([NH2:31])=[CH:29][C:28]=2[O:34][CH3:35])[CH:26]=1.OS(O)(=O)=O.CCOC(C)=O>CN1C(=O)CCC1>[Cl:21][C:22]1[N:23]=[CH:24][N:25]([C:27]2[CH:33]=[CH:32][C:30]([NH:31][C:2]3[N:3]=[C:4]([NH:17][CH:18]4[CH2:20][CH2:19]4)[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:29][C:28]=2[O:34][CH3:35])[CH:26]=1

Participants

6

Reactant 4

HCID 1118Sulfuric AcidHCID 8857Ethyl AcetateHCID 580757574-(4-chloro-1H-imidazol-1-yl)-3-methoxyanilineHCID 580758182-chloro-N-cyclopropyl-7-phenyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-amine

Product 1

HCID 50913638N2-(4-(4-chloro-1H-imidazol-1-yl)-3-methoxyphenyl)-N4-cyclopropyl-7-phenyl-6,7-dihydro-5H-cyclopenta[d]pyrimidine-2,4-diamineYield 69.1%

Reagents, catalysts & solvents 1

HCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
97 °C

Procedure

To a mixture of 2-chloro-N-cyclopropyl-7-phenyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-amine (175 mg, 0.612 mmol) and 4-(4-chloro-1H-imidazol-1-yl)-3-methoxyaniline (151 mg, 0.674 mmol) in NMP (2 mL) was added Conc. H2SO4 (0.046 mL, 0.857 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-cyclopropyl-7-phenyl-6,7-dihydro-5H-cyclopenta[d]pyrimidine-2,4-diamine (200 mg, 0.423 mmol, 69.1% yield). LC-MS (M+H)+=473.10. 1H NMR (500 MHz, CDCl3) δ ppm 7.81 (1H, d, J=1.8 Hz), 7.51 (1H, d, J=1.5 Hz), 7.44 (1H, s), 7.27-7.35 (2H, m), 7.19-7.25 (3H, m), 6.99-7.06 (2H, m), 6.95 (1H, d, J=8.2 Hz), 4.89 (1H, br. s.), 4.20 (1H, t, J=8.2 Hz), 3.45 (3H, s), 2.92 (1H, td, J=6.7, 3.1 Hz), 2.76-2.86 (1H, m), 2.59-2.75 (2H, m), 2.07-2.14 (1H, m), 0.85-0.91 (2H, m), 0.63-0.70 (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-212d41b2fbb048738f5a1832cadcf173
Source dataset
uspto-grants-2014_01
Patent number
US08637525B2

Reaction notes

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