Acetic Acid → 1-(2-methoxy-4-(4-(methylamino)-7-phenyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-ylamino)phenyl)-1H-imidazole-4-carbonitrile

HRID 451195Notes

Reaction equation

HRID 451195 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.[NH2:19][C:20]1[CH:25]=[CH:24][C:23]([N:26]2[CH:30]=[C:29]([C:31]#[N:32])[N:28]=[CH:27]2)=[C:22]([O:33][CH3:34])[CH:21]=1.CC(O)=O.[OH-].[Na+]>O1CCOCC1>[CH3:34][O:33][C:22]1[CH:21]=[C:20]([NH:19][C:2]2[N:3]=[C:4]([NH:17][CH3:18])[C:5]3[CH2:10][CH2:9][CH:8]([C:11]4[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=4)[C:6]=3[N:7]=2)[CH:25]=[CH:24][C:23]=1[N:26]1[CH:30]=[C:29]([C:31]#[N:32])[N:28]=[CH:27]1

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 14798Sodium HydroxideHCID 580752952-chloro-N-methyl-7-phenyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-amineHCID 667086684-(4-cyano-1H-imidazol-1-yl)-3-methoxyaniline

Product 1

HCID 509129111-(2-methoxy-4-(4-(methylamino)-7-phenyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-ylamino)phenyl)-1H-imidazole-4-carbonitrileYield 22.56%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

To a solution of 2-chloro-N-methyl-7-phenyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-amine (Preparation Ga) (150 mg, 0.578 mmol) in Dioxane (Ratio: 1, Volume: 1013 μl) was added 1-(4-amino-2-methoxyphenyl)-1H-imidazole-4-carbonitrile (Preparation AA) (124 mg, 0.578 mmol), and AcOH (Ratio: 1.000, Volume: 1013 μl). The resulting mixture was brought to 100° C. in a sealed vial and stirred overnight. The mixture was brought to pH 8 by the addition of 1 N aqueous sodium Hydroxide. The resulting mixture was extracted with EtOAc (3×1 mL). The combined extracts were dried over MgSO4, filtered and concentrated in vacuo. Purification by prep HPLC (Waters Sunfire C18, 50×250 mm, acetonitrile/H2O/ammonium acetate) gave 1-(2-methoxy-4-(4-(methylamino)-7-phenyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-ylamino)phenyl)-1H-imidazole-4-carbonitrile (57 mg, 0.130 mmol, 22.56% yield). LC-MS (M+H)+=438.2. 1H NMR (500 MHz, MeOD) δ ppm 8.02-8.08 (2H, m), 7.90-7.94 (1H, m), 7.31 (2H, t, J=7.63 Hz), 7.16-7.24 (4H, m), 6.99 (1H, dd, J=8.55, 2.14 Hz), 4.18 (1H, t, J=8.09 Hz), 3.56 (3H, s), 3.07 (3H, s), 2.76-2.84 (1H, m), 2.59-2.74 (2H, m), 1.98-2.05 (1H, m). The racemic mixture was separated by chiral chromatography to afford the enantiomers Example 204A and 204B.

Workup

  1. customwas brought to 100° C.
  2. extractionThe resulting mixture was extracted with EtOAc (3×1 mL)
  3. dry with materialThe combined extracts were dried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customPurification by prep HPLC (Waters Sunfire C18, 50×250 mm, acetonitrile/H2O/ammonium acetate)

Sources & evidence

ORD record
ord-9537ed9214054a88af0c23ea41639044
Source dataset
uspto-grants-2013_07
Patent number
US08486952B2

Reaction notes

Loading…