Iodoacetamide → HCID 10218048, compound

HRID 2068115Notes

Reaction equation

HRID 2068115 reaction equation
[F:1][C:2]1[C:10]([O:11][C:12]2[C:21]3[C:16](=[CH:17][C:18]([O:24][CH2:25][CH2:26][CH2:27][N:28]4[CH2:33][CH2:32][NH:31][CH2:30][CH2:29]4)=[C:19]([O:22][CH3:23])[CH:20]=3)[N:15]=[CH:14][N:13]=2)=[CH:9][CH:8]=[C:7]2[C:3]=1[CH:4]=[C:5]([CH3:34])[NH:6]2.I[CH2:36][C:37]([NH2:39])=[O:38]>C(#N)C>[C:37]([CH2:36][N:31]1[CH2:32][CH2:33][N:28]([CH2:27][CH2:26][CH2:25][O:24][C:18]2[CH:17]=[C:16]3[C:21]([C:12]([O:11][C:10]4[C:2]([F:1])=[C:3]5[C:7](=[CH:8][CH:9]=4)[NH:6][C:5]([CH3:34])=[CH:4]5)=[N:13][CH:14]=[N:15]3)=[CH:20][C:19]=2[O:22][CH3:23])[CH2:29][CH2:30]1)(=[O:38])[NH2:39]

Participants

4

Reactant 2

HCID 3727IodoacetamideHCID 58960233HCID 58960233, compound

Product 1

HCID 10218048HCID 10218048, compoundYield 32%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

A mixture of 4-[(4-fluoro-2-methyl-1H-indol-5-yl)oxy]-6-methoxy-7-(3-piperazin-1-ylpropoxy)quinazoline (370 mg, 0.8 mmol), (prepared as described for the starting material in Example 15), iodoacetamide (162 mg, 0.88 mmol) and N,N-diisopropylethylanmine (230 mg, 1.80 mmol) in acetonitrile (10 ml) was stirred at reflux for 1 hour and allowed to cool to ambient temperature. The solvent was removed under vacuum and the residue purified by column chromatography eluting with methylene chloride/methanol (saturated with ammonia) (92/8) solvent. The relevant fractions were combined and evaporated under vacuum to give a solid which was triturated with acetone, filtered and dried to give 7-[3-(4-carbamoylmethylpiperazin-1-yl)propoxy]-4-[(4-fluoro-2-methyl-1H-indol-5-yl)oxy]-6-methoxyquinazoline (132 mg, 32%).

Workup

  1. custom(prepared
  2. temperatureat reflux for 1 hour
  3. customThe solvent was removed under vacuum
  4. customthe residue purified by column chromatography
  5. washeluting with methylene chloride/methanol (saturated with ammonia) (92/8) solvent
  6. customevaporated under vacuum
  7. customto give a solid which
  8. customwas triturated with acetone
  9. filtrationfiltered
  10. customdried

Sources & evidence

ORD record
ord-1ca230a8c0014712871d52bd727240a8
Source dataset
uspto-grants-2012_10
Patent number
US08293902B2

Reaction notes

Loading…