Isobutyryl chloride → 4-[(4-fluoro-2-methyl-1H-indol-5-yl)oxy]-7-[(1-isobutyrylpiperidin-4-yl)methoxy]-6-methoxyquinazoline

HRID 916432Notes

Reaction equation

HRID 916432 reaction equation
C(N(C(C)C)CC)(C)C.[C:10](Cl)(=[O:14])[CH:11]([CH3:13])[CH3:12].[F:16][C:17]1[C:25]([O:26][C:27]2[C:36]3[C:31](=[CH:32][C:33]([O:39][CH2:40][CH:41]4[CH2:46][CH2:45][NH:44][CH2:43][CH2:42]4)=[C:34]([O:37][CH3:38])[CH:35]=3)[N:30]=[CH:29][N:28]=2)=[CH:24][CH:23]=[C:22]2[C:18]=1[CH:19]=[C:20]([CH3:47])[NH:21]2>C(Cl)Cl>[F:16][C:17]1[C:25]([O:26][C:27]2[C:36]3[C:31](=[CH:32][C:33]([O:39][CH2:40][CH:41]4[CH2:46][CH2:45][N:44]([C:10](=[O:14])[CH:11]([CH3:13])[CH3:12])[CH2:43][CH2:42]4)=[C:34]([O:37][CH3:38])[CH:35]=3)[N:30]=[CH:29][N:28]=2)=[CH:24][CH:23]=[C:22]2[C:18]=1[CH:19]=[C:20]([CH3:47])[NH:21]2

Participants

5

Reactant 3

HCID 62325Isobutyryl chlorideHCID 81531DiisopropylethylamineHCID 589602204-[(4-fluoro-2-methyl-1H-indol-5-yl)oxy]-6-methoxy-7-(piperidin-4-ylmethoxy)quinazoline

Product 1

HCID 102178804-[(4-fluoro-2-methyl-1H-indol-5-yl)oxy]-7-[(1-isobutyrylpiperidin-4-yl)methoxy]-6-methoxyquinazolineYield 52.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

Diisopropylethylamine (72 μl, 0.41 mmol) and isobutyryl chloride (44 mg, 0.41 mmol), in methylene chloride (0.5 ml) were added to a suspension of 4-[(4-fluoro-2-methyl-1H-indol-5-yl)oxy]-6-methoxy-7-(piperidin-4-ylmethoxy)quinazoline (150 mg, 0.34 mmol), (prepared as described for the starting material in Example 11), in methylene chloride (4 ml). After a few minutes all the material had gone into solution. The mixture was stirred for 3 hours at ambient temperature, washed with saturated sodium hydrogen carbonate solution, dried (MgSO4) and concentrated under reduced pressure. Column chromatography of the residue, eluting with 2% methanol/methylene chloride gave 4-[(4-fluoro-2-methyl-1H-indol-5-yl)oxy]-7-[(1-isobutyrylpiperidin-4-yl)methoxy]-6-methoxyquinazoline (90 mg, 52%).

Workup

  1. custom(prepared
  2. waitAfter a few minutes all the material had gone into solution
  3. washwashed with saturated sodium hydrogen carbonate solution
  4. dry with materialdried (MgSO4)
  5. concentrationconcentrated under reduced pressure
  6. washColumn chromatography of the residue, eluting with 2% methanol/methylene chloride

Sources & evidence

ORD record
ord-98d41ae789d44cbea019a003d685e270
Source dataset
uspto-grants-2007_09
Patent number
US07268230B2

Reaction notes

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