Triphenylphosphine → 4-Chloro-7-{2-[4-(2-fluoroethyl)piperazin-1-yl]ethoxy}-6-methoxyquinazoline

HRID 916482Notes

Reaction equation

HRID 916482 reaction equation
[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][C:8]([OH:14])=[C:9]([O:12][CH3:13])[CH:10]=2)[N:5]=[CH:4][N:3]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[F:34][CH2:35][CH2:36][N:37]1[CH2:42][CH2:41][N:40]([CH2:43][CH2:44]O)[CH2:39][CH2:38]1>ClCCl>[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][C:8]([O:14][CH2:44][CH2:43][N:40]3[CH2:41][CH2:42][N:37]([CH2:36][CH2:35][F:34])[CH2:38][CH2:39]3)=[C:9]([O:12][CH3:13])[CH:10]=2)[N:5]=[CH:4][N:3]=1

Participants

5

Reactant 3

HCID 11776TriphenylphosphineHCID 450996492-[4-(2-Fluoroethyl)piperazin-1-YL]ethanolHCID 1357422514-Chloro-6-methoxyquinazolin-7-ol

Product 1

HCID 589602314-Chloro-7-{2-[4-(2-fluoroethyl)piperazin-1-yl]ethoxy}-6-methoxyquinazolineYield 67.6%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

4-Chloro-7-hydroxy-6-methoxyquinazoline (146 mg, 0.69 mmol), (prepared as described for the starting material in Example 4), was suspended in dichloromethane (7.5 ml). Triphenylphosphine (254 mg, 0.97 mmol) and 2-[4-(2-fluoroethyl)piperazin-1-yl]ethanol (134 mg, 0.76 mmol) were added. Diisopropyl azadicarboxylate (165 μl, 0.83 mmol) was then added dropwise. The reaction mixture was stirred for 2.25 hours at ambient temperature and then loaded directly onto a silica column and eluted with methylene chloride/methanol (92/8) to give 4-chloro-7-{2-[4-(2-fluoroethyl)piperazin-1-yl]ethoxy}-6-methoxyquinazoline (172 mg, 67%).

Workup

  1. additionDiisopropyl azadicarboxylate (165 μl, 0.83 mmol) was then added dropwise
  2. washeluted with methylene chloride/methanol (92/8)

Sources & evidence

ORD record
ord-8cc88f63dac94869950411f3a95b1cde
Source dataset
uspto-grants-2007_09
Patent number
US07268230B2

Reaction notes

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