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

HRID 475914Notes

Reaction equation

HRID 475914 reaction equation
Cl[C:2]1[N:3]=[C:4]([NH:19][CH3:20])[C:5]2[CH2:10][CH2:9][CH:8]([C:11]3[CH:16]=[CH:15][C:14]([F:17])=[CH:13][C:12]=3[F:18])[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>C1COCC1.C(O)(=O)C>[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:19][CH3:20])[C:5]4[CH2:10][CH2:9][CH:8]([C:11]5[CH:16]=[CH:15][C:14]([F:17])=[CH:13][C:12]=5[F:18])[C:6]=4[N:7]=3)=[CH:29][C:28]=2[O:34][CH3:35])[CH:26]=1

Participants

5

Reactant 2

HCID 580757472-chloro-7-(2,4-difluorophenyl)-N-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-amineHCID 580757574-(4-chloro-1H-imidazol-1-yl)-3-methoxyaniline

Product 1

HCID 58075702N2-(4-(4-chloro-1H-imidazol-1-yl)-3-methoxyphenyl)-7-(2,4-difluorophenyl)-N4-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidine-2,4-diamineYield 59.6%

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 8028TetrahydrofuranSolvent

Procedure

A solution of 2-chloro-7-(2,4-difluorophenyl)-N-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-amine (184.6 mg, 0.624 mmol) and 4-(4-chloro-1H-imidazol-1-yl)-3-methoxyaniline (140 mg, 0.624 mmol) in THF (1095 μL) and acetic acid (1095 μL) was heated 80° C. in a capped vial overnight. The solvent was evaporated in vacuum and the residue was partitioned between aqueous sodium bicarbonate solution and dichloromethane. The organic layer was separated and the aqueous layer 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)-7-(2,4-difluorophenyl)-N4-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidine-2,4-diamine (179.6 mg, 0.372 mmol, 59.6% yield) as brown solid. LC-MS (M+H)+=483.1. 1H NMR (500 MHz, CDCl3) δ ppm 7.97 (1H, d, J=2.1 Hz), 7.49 (1H, d, J=1.5 Hz), 7.01-7.10 (2H, m), 7.00 (1H, d, J=1.5 Hz), 6.73-6.84 (3H, m), 4.44 (1H, s), 3.61 (3H, s), 3.11 (3H, d, J=4.9 Hz), 2.59-2.77 (2H, m), 1.95-2.05 (2H, m).

Workup

  1. customThe solvent was evaporated in vacuum
  2. customthe residue was partitioned between aqueous sodium bicarbonate solution and dichloromethane
  3. customThe organic layer was separated
  4. extractionthe aqueous layer was extracted with dichloromethane
  5. dry with materialthe combined organic extracts were dried over anhydrous magnesium sulfate
  6. filtrationfiltered
  7. customThe solvent was removed in vacuum
  8. customthe residue was purified by column chromatography on silica gel

Sources & evidence

ORD record
ord-99711ed016f94f26ac71440398d8dd50
Source dataset
uspto-grants-2014_01
Patent number
US08637525B2

Reaction notes

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