Triphenylphosphine → 7-(3-(4-Acetylpiperazin-1-yl)propoxy)-4-chloro-6-methoxyquinazoline

HRID 916406Notes

Reaction equation

HRID 916406 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.[C:15]([N:18]1[CH2:23][CH2:22][N:21]([CH2:24][CH2:25][CH2:26]O)[CH2:20][CH2:19]1)(=[O:17])[CH3:16].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OC(C)C)=O)=NC(OC(C)C)=O>ClCCl>[CH3:8][CH2:7][CH2:6][CH:11]([CH3:2])[CH3:10].[C:15]([N:18]1[CH2:23][CH2:22][N:21]([CH2:24][CH2:25][CH2:26][O:14][C:8]2[CH:7]=[C:6]3[C:11]([C:2]([Cl:1])=[N:3][CH:4]=[N:5]3)=[CH:10][C:9]=2[O:12][CH3:13])[CH2:20][CH2:19]1)(=[O:17])[CH3:16]

Participants

7

Reactant 4

HCID 11776TriphenylphosphineHCID 75555Diisopropyl diazene-1,2-dicarboxylateHCID 114467711-(4-(3-Hydroxypropyl)piperazin-1-yl)ethan-1-oneHCID 1357422514-Chloro-6-methoxyquinazolin-7-ol

Product 2

HCID 78922-MethylpentaneHCID 589602297-(3-(4-Acetylpiperazin-1-yl)propoxy)-4-chloro-6-methoxyquinazolineYield 147.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

4-Chloro-7-hydroxy-6-methoxyquinazoline (3 g, 14.2 mmol), (prepared as described for the starting material in Example 4), 3-(4-acetylpiperazin-1-yl)propan-1-ol (3.2 g, 17.1 mmol), (prepared as described for the starting material in this example hereinbefore), and triphenylphosphine (4.5 g, 17.1 mmol) were stirred together in dichloromethane (140 ml). Diisopropyl azodicarboxylate (3.4 ml, 17.1 mmol) was added dropwise and an ice/water bath used to keep the temperature of the reaction mixture below 10° C. After the addition, the reaction mixture was allowed to warm to ambient temperature and stirred overnight. The mixture was concentrated under reduced pressure. Column chromatography of the residue (2:1 iso-hexane:ethyl acetate then 3%-5% methanol/dichloromethane) gave 7-[3-(4-acetylpiperazin-1-yl)propoxy]-4-chloro-6-methoxyquinazoline (3.96 g, 74%) as a white solid.

Workup

  1. custom(prepared
  2. customan ice/water bath used
  3. customthe temperature of the reaction mixture below 10° C
  4. additionAfter the addition
  5. concentrationThe mixture was concentrated under reduced pressure

Sources & evidence

ORD record
ord-4afea6315ae542f1bd3f35b77daa2c33
Source dataset
uspto-grants-2007_09
Patent number
US07268230B2

Reaction notes

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