Diisopropylethylamine → 2-chloro-7-(2,4-difluorophenyl)-N-(5-(2-(3-methyl-1H-1,2,4-triazol-1-yl)-5-nitrophenoxy)pentan-2-yl)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-amine

HRID 474271Notes

Reaction equation

HRID 474271 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][C:14]([F:17])=[CH:13][C:12]=3[F:18])[C:6]=2[N:7]=1.C(N(C(C)C)CC)(C)C.[CH3:29][C:30]1[N:34]=[CH:33][N:32]([C:35]2[CH:47]=[CH:46][C:45]([N+:48]([O-:50])=[O:49])=[CH:44][C:36]=2[O:37][CH2:38][CH2:39][CH2:40][CH:41]([NH2:43])[CH3:42])[N:31]=1>C(#N)C>[Cl:1][C:2]1[N:3]=[C:4]([NH:43][CH:41]([CH2:40][CH2:39][CH2:38][O:37][C:36]2[CH:44]=[C:45]([N+:48]([O-:50])=[O:49])[CH:46]=[CH:47][C:35]=2[N:32]2[CH:33]=[N:34][C:30]([CH3:29])=[N:31]2)[CH3:42])[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

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 580755852,4-Dichloro-7-(2,4-difluorophenyl)-6,7-dihydro-5H-cyclopenta[D]pyrimidineHCID 666655155-(2-(3-methyl-1H-1,2,4-triazol-1-yl)-5-nitrophenoxy)pentan-2-amine

Product 1

HCID 866681162-chloro-7-(2,4-difluorophenyl)-N-(5-(2-(3-methyl-1H-1,2,4-triazol-1-yl)-5-nitrophenoxy)pentan-2-yl)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-amineYield 37.9%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

To a solution of 2,4-dichloro-7-(2,4-difluorophenyl)-6,7-dihydro-5H-cyclopenta[d]pyrimidine (907 mg, 3.01 mmol) in acetonitrile (150 mL) was added diisopropylethylamine (1.05 g, 6.03 mmol) followed by 5-(2-(3-methyl-1H-1,2,4-triazol-1-yl)-5-nitrophenoxy)pentan-2-amine (920 mg, 3.01 mmol) at room temperature. The reaction mixture was stirred at rt for 18 h while monitoring by LC-MS. The solvent was removed under reduced pressure and the residue was purified by column chromatography (60-120 mesh silica) using 2-3% of methanol in chloroform to give 2-chloro-7-(2,4-difluorophenyl)-N-(5-(2-(3-methyl-1H-1,2,4-triazol-1-yl)-5-nitrophenoxy)pentan-2-yl)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-amine as a yellow solid (650 mg, 1.140 mmol, 37.8% yield). LC-MS (M+H)+=570.0. 1H NMR: (400 MHz, CDCl3) δ ppm 8.85 (1H, s), 8.07 (1H, d, J=8.4 Hz), 8.00-7.96 (2H, m), 7.00-6.97 (1H, m), 6.81-6.78 (2H, m), 4.47-4.31 (5H, m), 2.72-2.64 (3H, m), 2.50 (3H, s), 2.04-1.98 (3H, m), 1.78-1.74 (2H, m), 1.32-1.25 (3H, m).

Workup

  1. customThe solvent was removed under reduced pressure
  2. customthe residue was purified by column chromatography (60-120 mesh silica)

Sources & evidence

ORD record
ord-31314192d9e2474287e83dd25f80b29f
Source dataset
uspto-grants-2014_01
Patent number
US08637523B2

Reaction notes

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