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

HRID 474264Notes

Reaction equation

HRID 474264 reaction equation
[Cl:1][C:2]1[N:3]=[C:4]([NH:18][CH2:19][CH2:20][NH2:21])[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[CH2:23][CH2:24][O:25][C:26]1[CH:33]=[C:32]([N+:34]([O-:36])=[O:35])[CH:31]=[CH:30][C:27]=1[C:28]#[N:29]>CN(C=O)C>[Cl:1][C:2]1[N:3]=[C:4]([NH:18][CH2:19][CH2:20][NH:21][CH2:23][CH2:24][O:25][C:26]2[CH:33]=[C:32]([N+:34]([O-:36])=[O:35])[CH:31]=[CH:30][C:27]=2[C:28]#[N:29])[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 86668112N1-(2-chloro-7-(4-fluorophenyl)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)ethane-1,2-diamine

Product 1

HCID 866681112-(2-(2-(2-chloro-7-(4-fluorophenyl)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-ylamino)ethylamino)ethoxy)-4-nitrobenzonitrileYield 21.7%

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)ethane-1,2-diamine {Preparation Sc Step (1), 1.0 g, 3.265 mmol} in DMF (5 mL) was added TEA (0.495 g, 4.89 mmol) followed by 2-(2-bromoethoxy)-4-nitrobenzonitrile (Preparation N, 1.05 g, 3.91 mmol) at room temperature. The reaction mixture was stirred at rt 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)ethylamino)ethoxy)-4-nitrobenzonitrile (0.35 g, 21.7%) as a light yellow solid. LC-MS (M+H)+=497.2. 1H NMR (400 MHz, CDCl3) δ ppm 7.93-7.91 (1H, d, J=6.8 Hz), 7.90 (1H, s), 7.86-7.85 (1H, m), 7.12-7.00 (2H, m), 6.98-6.96 (2H, m), 5.30 (1H, br s), 4.34-4.32 (2H, m), 4.26-4.24 (1H, m), 3.70-3.66 (2H, m), 3.21-3.19 (2H, m), 3.04-3.02 (2H, m), 2.78-2.63 (3H, m), 1.99-1.98 (1H, m).

Workup

  1. customThe solvent was removed under reduced pressure

Sources & evidence

ORD record
ord-283b586d9fb749a78ebe23db805d2259
Source dataset
uspto-grants-2014_01
Patent number
US08637523B2

Reaction notes

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