Diisopropylethylamine → 2-chloro-N-(5-isopropyl-2-methylphenyl)-7-phenyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-amine

HRID 451031Notes

Reaction equation

HRID 451031 reaction equation
[Cl:1][C:2]1[N:3]=[C:4](Cl)[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.[CH:18]([C:21]1[CH:22]=[CH:23][C:24]([CH3:28])=[C:25]([CH:27]=1)[NH2:26])([CH3:20])[CH3:19].CCN(C(C)C)C(C)C>CN1C(=O)CCC1.CCOC(C)=O>[Cl:1][C:2]1[N:3]=[C:4]([NH:26][C:25]2[CH:27]=[C:21]([CH:18]([CH3:19])[CH3:20])[CH:22]=[CH:23][C:24]=2[CH3:28])[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

Participants

6

Reactant 3

HCID 81531DiisopropylethylamineHCID 1374142-Amino-p-cymeneHCID 580754632,4-Dichloro-7-phenyl-6,7-dihydro-5H-cyclopenta[D]pyrimidine

Product 1

HCID 580755202-chloro-N-(5-isopropyl-2-methylphenyl)-7-phenyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-amineYield 30.9%

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

To a solution of 2,4-dichloro-7-phenyl-6,7-dihydro-5H-cyclopenta[d]pyrimidine (500 mg, 1.886 mmol) in NMP (Volume: 7543 n1) was added 5-isopropyl-2-methylaniline (281 mg, 1.886 mmol) and DIPEA (329 μl, 1.886 mmol). The resulting mixture was brought to 120° C. and stirred for 2 h. The mixture was then diluted with EtOAc (25 mL), washed with water (2×10 mL), brine (10 mL), dried over MgSO4, filtered, and concentrated in vacuo. Purification by flash chromatography (Silica, Thomson 40 g, 0-35% EtOAc/Hexanes) gave 2-chloro-N-(5-isopropyl-2-methylphenyl)-7-phenyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-amine (81421-078-01) (220 mg, 0.582 mmol, 30.9% yield). LC-MS (M+H)+=378.1. 1H NMR (500 MHz, MeOD) δ ppm 7.30-7.41 (3H, m), 7.19-7.26 (3H, m), 7.16 (2H, d, J=7.93 Hz), 7.11 (1H, d, J=7.63 Hz), 4.27 (1H, t, J=7.63 Hz), 2.91 (1H, ddd, J=13.89, 6.87, 6.71 Hz), 2.77-2.86 (1H, m), 2.61-2.76 (2H, m), 2.24 (3H, s), 2.03-2.13 (1H, m), 1.27 (5H, dd, J=7.02, 1.53 Hz).

Workup

  1. customwas brought to 120° C.
  2. washwashed with water (2×10 mL), brine (10 mL)
  3. dry with materialdried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customPurification by flash chromatography (Silica, Thomson 40 g, 0-35% EtOAc/Hexanes)

Sources & evidence

ORD record
ord-03d8f7c7586e4fbf833431f506d9a871
Source dataset
uspto-grants-2013_07
Patent number
US08486952B2

Reaction notes

Loading…