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

HRID 916442Notes

Reaction equation

HRID 916442 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

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 6344DichloromethaneSolvent

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-da592e7fb86c4c68b4b97c18eb454af3
Source dataset
uspto-grants-2007_09
Patent number
US07268230B2

Reaction notes

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