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

HRID 2068072Notes

Reaction equation

HRID 2068072 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 bad 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 bad 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-bd148fd7a3084223a3e92602265bf32f
Source dataset
uspto-grants-2012_10
Patent number
US08293902B2

Reaction notes

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