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

HRID 2068050Notes

Reaction equation

HRID 2068050 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([O-])=O)=NC([O-])=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 114467711-(4-(3-Hydroxypropyl)piperazin-1-yl)ethan-1-oneHCID 51573101N-carboxylatoiminocarbamateHCID 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). Dbsopropyl 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-e5b7f790de064099b9c7dcb3bb8e3e78
Source dataset
uspto-grants-2012_10
Patent number
US08293902B2

Reaction notes

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