2-(2-Bromoethoxy)-4-nitrobenzonitrile → 2-(2-((2-(2-chloro-7-(4-fluorophenyl)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-ylamino)ethyl)(methyl)amino)ethoxy)-4-nitrobenzonitrile

HRID 474265Notes

Reaction equation

HRID 474265 reaction equation
[Cl:1][C:2]1[N:3]=[C:4]([NH:18][CH2:19][CH2:20][NH:21][CH3:22])[C:5]2[CH2:10][CH2:9][CH:8]([C:11]3[CH:16]=[CH:15][C:14]([F:17])=[CH:13][CH:12]=3)[C:6]=2[N:7]=1.Br[CH2:24][CH2:25][O:26][C:27]1[CH:34]=[C:33]([N+:35]([O-:37])=[O:36])[CH:32]=[CH:31][C:28]=1[C:29]#[N:30]>CN(C=O)C>[Cl:1][C:2]1[N:3]=[C:4]([NH:18][CH2:19][CH2:20][N:21]([CH3:22])[CH2:24][CH2:25][O:26][C:27]2[CH:34]=[C:33]([N+:35]([O-:37])=[O:36])[CH:32]=[CH:31][C:28]=2[C:29]#[N:30])[C:5]2[CH2:10][CH2:9][CH:8]([C:11]3[CH:16]=[CH:15][C:14]([F:17])=[CH:13][CH:12]=3)[C:6]=2[N:7]=1

Participants

4

Reactant 2

HCID 666658762-(2-Bromoethoxy)-4-nitrobenzonitrileHCID 86668110N1-(2-chloro-7-(4-fluorophenyl)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)-N2-methylethane-1,2-diamine

Product 1

HCID 866681132-(2-((2-(2-chloro-7-(4-fluorophenyl)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-ylamino)ethyl)(methyl)amino)ethoxy)-4-nitrobenzonitrileYield 37.68%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of N1-(2-chloro-7-(4-fluorophenyl)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)-N2-methylethane-1,2-diamine {Preparation Sd Step (1), 0.5 g, 1.56 mmol} in DMF (5 mL) was added TEA (0.234 g, 2.34 mmol) followed by 2-(2-bromoethoxy)-4-nitrobenzonitrile (0.423 g, 1.56 mmol) at room temperature. The reaction mixture was stirred at room temperature for 18 h. The solvent was removed under reduced pressure and the residue was taken in dichloromethane (5 mL) and silica (1 g). The resultant slurry of the compound in silica was subjected to flash chromatography using a Teledyne Isco instrument (12 g RediSep silica column, 10% methanol in chloroform) to get 2-(2-((2-(2-chloro-7-(4-fluorophenyl)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-ylamino)ethyl)(methyl)amino)ethoxy)-4-nitrobenzonitrile (0.3 g, 37.68%) as a dark brown solid. LC-MS (M+H)+=511.2. 1H NMR (400 MHz, CDCl3) δ ppm 7.91-7.89 (1H, m), 7.85 (1H, s), 7.72-7.70 (1H, m), 7.14-7.10 (2H, m), 6.98-6.96 (2H, m), 4.42-4.39 (2H, m), 4.17-4.15 (1H, m), 3.66-3.56 (2H, m), 3.49 (3H, s), 3.35-3.26 (2H, m), 3.18-3.12 (4H, m), 2.78-2.63 (1H, m), 1.99-1.98 (1H, m).

Workup

  1. customThe solvent was removed under reduced pressure

Sources & evidence

ORD record
ord-863f58eba0da4624bd2b0c3b4bfc02ea
Source dataset
uspto-grants-2014_01
Patent number
US08637523B2

Reaction notes

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