Triphenylphosphine → 4-Chloro-6-methoxy-7-[3-(4-prop-2-yn-1-ylpiperazin-1-yl)propoxy]quinazoline

HRID 2068125Notes

Reaction equation

HRID 2068125 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.[CH2:34]([N:37]1[CH2:42][CH2:41][N:40]([CH2:43][CH2:44][CH2:45]O)[CH2:39][CH2:38]1)[C:35]#[CH:36]>ClCCl>[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][C:8]([O:14][CH2:45][CH2:44][CH2:43][N:40]3[CH2:39][CH2:38][N:37]([CH2:34][C:35]#[CH:36])[CH2:42][CH2:41]3)=[C:9]([O:12][CH3:13])[CH:10]=2)[N:5]=[CH:4][N:3]=1

Participants

5

Reactant 3

HCID 11776TriphenylphosphineHCID 450998243-(4-Prop-2-YN-1-ylpiperazin-1-YL)propan-1-OLHCID 1357422514-Chloro-6-methoxyquinazolin-7-ol

Product 1

HCID 589602354-Chloro-6-methoxy-7-[3-(4-prop-2-yn-1-ylpiperazin-1-yl)propoxy]quinazolineYield 77%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

4-Chloro-7-hydroxy-6-methoxyquinazoline (300 mg, 1.42 mmol), (prepared as described for the starting material in Example 4), was suspended in dichloromethane (15 ml). Triphenylphosphine (523 mg, 2 mmol) and 3-(4-prop-2-yn-1-ylpiperazin-1-yl)propan-1-ol (267 mg, 1.46 mmol) were added. Diisopropyl azadicarboxylate (340 μl, 1.71 mmol) was then added dropwise. The reaction mixture was stirred for 1.25 hours at ambient temperature and then loaded directly onto a silica column, and eluted with methylene chloride/methanol (90/8 followed by 90/10) to give 4-chloro-6-methoxy-7-[3-(4-prop-2-yn-1-ylpiperazin-1-yl)propoxy]quinazoline (409 mg, 77%).

Workup

  1. additionDiisopropyl azadicarboxylate (340 μl, 1.71 mmol) was then added dropwise
  2. washeluted with methylene chloride/methanol (90/8 followed by 90/10)

Sources & evidence

ORD record
ord-4ac9bb9ccf034c2d9476593e58eafda8
Source dataset
uspto-grants-2012_10
Patent number
US08293902B2

Reaction notes

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