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Triphenylphosphine → 7-{3-[4-(2-fluoroethyl)piperazin-1-yl]propoxy}-4-[(4-fluoro-2-methyl-1H-indol-5-yl)oxy]-6-methoxyquinazoline

HRID 2068081
Notes
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Reaction equation

HRID 2068081 reaction equation
[F:1][CH2:2][CH2:3][N:4]1[CH2:9][CH2:8][N:7]([CH2:10][CH2:11][CH2:12][OH:13])[CH2:6][CH2:5]1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[F:33][C:34]1[C:42]([O:43][C:44]2[C:53]3[C:48](=[CH:49][C:50](O)=[C:51]([O:54][CH3:55])[CH:52]=3)[N:47]=[CH:46][N:45]=2)=[CH:41][CH:40]=[C:39]2[C:35]=1[CH:36]=[C:37]([CH3:57])[NH:38]2>ClCCl>[F:1][CH2:2][CH2:3][N:4]1[CH2:9][CH2:8][N:7]([CH2:10][CH2:11][CH2:12][O:13][C:50]2[CH:49]=[C:48]3[C:53]([C:44]([O:43][C:42]4[C:34]([F:33])=[C:35]5[C:39](=[CH:40][CH:41]=4)[NH:38][C:37]([CH3:57])=[CH:36]5)=[N:45][CH:46]=[N:47]3)=[CH:52][C:51]=2[O:54][CH3:55])[CH2:6][CH2:5]1
ParticipantsProcedureWorkupSources & evidenceReaction notes

Participants

5

Reactant 3

HCID 11776TriphenylphosphineHCID 451157673-[4-(2-Fluoroethyl)piperazin-1-YL]propan-1-OLHCID 1355308324-((4-Fluoro-2-methyl-1H-indol-5-yl)oxy)-6-methoxyquinazolin-7-ol

Product 1

HCID 101960587-{3-[4-(2-fluoroethyl)piperazin-1-yl]propoxy}-4-[(4-fluoro-2-methyl-1H-indol-5-yl)oxy]-6-methoxyquinazolineYield 83.2%

Reagents, catalysts & solvents 1

HCID 6344
Dichloromethane
Solvent

Procedure

Diisopropyl azadicarboxylate (230 μl, 1.17 mmol) was added dropwise to a solution of 3-[4-(2-fluoroethyl)piperazin-1-yl]propan-1-ol (203 mg, 1.07 mmol), triphenylphosphine (357 mg, 1.36 mmol) and 4-[(4-fluoro-2-methyl-1H-indol-5-yl)oxy]-7-hydroxy-6-methoxyquinazoline (330 mg, 0.97 mmol), (prepared as described for the starting material in Example 7), in dichloromethane (8.5 ml). The reaction mixture was stirred at ambient temperature for 1.5 hours and then loaded directly onto a silica column, eluting with a mixture of methanol in methylene chloride (11/89) to give 7-{3-[4-(2-fluoroethyl)piperazin-1-yl]propoxy}-4-[(4-fluoro-2-methyl-1H-indol-5-yl)oxy]-6-methoxyquinazoline (413 mg, 83%) as a white solid.

Workup

  1. custom(prepared
  2. washeluting with a mixture of methanol in methylene chloride (11/89)

Sources & evidence

ORD record
ord-75b52c1ec9254511809c229f0b3c777b
Source dataset
uspto-grants-2012_10
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US08293902B2

Reaction notes

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On this pageParticipantsProcedureWorkupSources & evidenceReaction notes