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

HRID 451182Notes

Reaction equation

HRID 451182 reaction equation
Cl[C:2]1[N:3]=[C:4]([NH:20][CH3:21])[C:5]2[CH2:10][CH2:9][CH:8]([C:11]3[CH:16]=[C:15]([F:17])[C:14]([F:18])=[C:13]([F:19])[CH:12]=3)[C:6]=2[N:7]=1.[F:22][C:23]1[CH:24]=[C:25]([CH:27]=[CH:28][C:29]=1[N:30]1[C:34]([CH3:35])=[N:33][CH:32]=[N:31]1)[NH2:26]>C(O)(=O)C.C1COCC1>[F:22][C:23]1[CH:24]=[C:25]([NH:26][C:2]2[N:3]=[C:4]([NH:20][CH3:21])[C:5]3[CH2:10][CH2:9][CH:8]([C:11]4[CH:16]=[C:15]([F:17])[C:14]([F:18])=[C:13]([F:19])[CH:12]=4)[C:6]=3[N:7]=2)[CH:27]=[CH:28][C:29]=1[N:30]1[C:34]([CH3:35])=[N:33][CH:32]=[N:31]1

Participants

5

Reactant 2

HCID 580756192-chloro-N-methyl-7-(3,4,5-trifluorophenyl)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-amineHCID 584144593-fluoro-4-(5-methyl-1H-1,2,4-triazol-1-yl)aniline

Product 1

HCID 58075626N2-(3-fluoro-4-(5-methyl-1H-1,2,4-triazol-1-yl)phenyl)-N4-methyl-7-(3,4,5-trifluorophenyl)-6,7-dihydro-5H-cyclopenta[d]pyrimidine-2,4-diamine

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
80 °C

Procedure

2-Chloro-N-methyl-7-(3,4,5-trifluorophenyl)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-amine (65.3 mg, 0.208 mmol) was added to a solution of 3-fluoro-4-(5-methyl-1H-1,2,4-triazol-1-yl)aniline (40 mg, 0.208 mmol) in acetic acid (2 mL) and THF (2.000 mL). The reaction mixture was heated at 80° C. overnight. Partial formation of the desired product was observed. The reaction mixture was heated at 130° C. for 6 h. The crude reaction mixture was purified by preparative HPLC. The appropriate fractions were evaporated to afford N2-(3-fluoro-4-(3-methyl-1H-1,2,4-triazol-1-yl)phenyl)-N4-methyl-7-(3,4,5-trifluorophenyl)-6,7-dihydro-5H-cyclopenta[d]pyrimidine-2,4-diamine, TFA salt (5.3 mg, 8.99 μmol, 4.32% yield). LC-MS (M+H)+=470.0. 1H NMR (500 MHz, CDCl3) δ ppm 12.17 (1H, s), 8.75 (1H, d, J=1.8 Hz), 8.05 (1H, dd, J=13.7, 2.1 Hz), 7.80 (1H, t, J=8.7 Hz), 7.44-7.65 (1H, m), 6.74-6.99 (2H, m), 5.33-5.66 (1H, m), 4.34-4.67 (1H, m), 3.42-3.74 (2H, m), 3.29 (3H, d, J=4.9 Hz), 2.70-2.99 (2H, m), 2.57 (2H, s), 2.14-2.38 (1H, m).

Sources & evidence

ORD record
ord-39546152c94f430b98e7512ea1cbf2a1
Source dataset
uspto-grants-2013_07
Patent number
US08486952B2

Reaction notes

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