Acetyl chloride → 6-[(1-acetylpiperidin-4-yl)methoxy]-4-[(4-fluoro-1H-indol-5-yl)oxy]-7-methoxyquinazoline

HRID 2068107Notes

Reaction equation

HRID 2068107 reaction equation
[F:1][C:2]1[C:10]([O:11][C:12]2[C:21]3[C:16](=[CH:17][C:18]([O:30][CH3:31])=[C:19]([O:22][CH2:23][CH:24]4[CH2:29][CH2:28][NH:27][CH2:26][CH2:25]4)[CH:20]=3)[N:15]=[CH:14][N:13]=2)=[CH:9][CH:8]=[C:7]2[C:3]=1[CH:4]=[CH:5][NH:6]2.C(N(C(C)C)CC)(C)C.[C:41](Cl)(=[O:43])[CH3:42]>ClCCl>[C:41]([N:27]1[CH2:28][CH2:29][CH:24]([CH2:23][O:22][C:19]2[CH:20]=[C:21]3[C:16](=[CH:17][C:18]=2[O:30][CH3:31])[N:15]=[CH:14][N:13]=[C:12]3[O:11][C:10]2[C:2]([F:1])=[C:3]3[C:7](=[CH:8][CH:9]=2)[NH:6][CH:5]=[CH:4]3)[CH2:25][CH2:26]1)(=[O:43])[CH3:42]

Participants

5

Reactant 3

HCID 6367Acetyl chlorideHCID 81531DiisopropylethylamineHCID 589602244-[(4-fluoro-1H-indol-5-yl)oxy]-7-methoxy-6-(piperidin-4-ylmethoxy)quinazoline

Product 1

HCID 102885866-[(1-acetylpiperidin-4-yl)methoxy]-4-[(4-fluoro-1H-indol-5-yl)oxy]-7-methoxyquinazolineYield 63%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

4-[(4-Fluoro-1H-indol-5-yl)oxy]-7-methoxy-6-(piperidin-4-ylmethoxy)quinazoline (210 mg, 0.50 mmol) was suspended in dichloromethane (7 ml) and diisopropylethylamine (104 μl, 0.60 mmol) and acetyl chloride (42 μl, 0.60 mmol) were added. All solid material went into solution. The mixture was stirred at ambient temperature overnight. The mixture was washed with brine, followed by saturated aqueous sodium hydrogen carbonate, dried (MgSO4) and concentrated under reduced pressure. The residue was purified by column chromatography eluting with methylene chloride/methanol (98/2) to give 6-[(1-acetylpipendin-4-yl)methoxy]-4-[(4-fluoro-1H-indol-5-yl)oxy]-7-methoxyquinazoline (146 mg, 63%) as a white foam.

Workup

  1. washThe mixture was washed with brine
  2. dry with materialdried (MgSO4)
  3. concentrationconcentrated under reduced pressure
  4. customThe residue was purified by column chromatography
  5. washeluting with methylene chloride/methanol (98/2)

Sources & evidence

ORD record
ord-46ca776c652f49478ef108304d627c72
Source dataset
uspto-grants-2012_10
Patent number
US08293902B2

Reaction notes

Loading…