Dichloromethane → HCID 178496235, compound

HRID 2182575Notes

Reaction equation

HRID 2182575 reaction equation
N(C(OCC)=O)=N[C:3](OCC)=[O:4].[Br:13][C:14]1[CH:33]=[CH:32][C:17]([NH:18][C:19]2[C:28]3[C:23](=[CH:24][C:25]([OH:31])=[C:26](OC)[CH:27]=3)[N:22]=[CH:21][N:20]=2)=[C:16]([F:34])[CH:15]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[CH3:54][O:55][CH2:56][CH2:57][O:58][CH2:59][CH2:60]O.C(Cl)[Cl:63]>>[ClH:63].[Br:13][C:14]1[CH:33]=[CH:32][C:17]([NH:18][C:19]2([O:4][CH3:3])[C:28]3[C:23](=[CH:24][C:25]([O:31][CH2:60][CH2:59][O:58][CH2:57][CH2:56][O:55][CH3:54])=[CH:26][CH:27]=3)[N:22]=[CH:21][NH:20]2)=[C:16]([F:34])[CH:15]=1

Participants

6

Reactant 5

HCID 6344DichloromethaneHCID 8134Diethylene Glycol Monomethyl EtherHCID 11776TriphenylphosphineHCID 220568ethyl N-ethoxycarbonyliminocarbamateHCID 1355038524-[(4-Bromo-2-fluorophenyl)amino]-6-methoxy-7-quinazolinol

Product 1

HCID 178496235HCID 178496235, compoundYield 34%

Procedure

Diethyl azodicarboxylate (236 μl, 1.5 mmol) was added dropwise to a mixture of 4-(4-bromo-2-fluoroanilino)-7-hydroxy-6-methoxyquinazoline (182 mg, 0.5 mmol), (prepared as described for the starting material in Example 48), triphenylphosphine (393 mg, 1.5 mmol) and 2-(2-methoxyethoxy)ethanol (84 μl, 0.7 mmol) in methylene chloride (7 ml) under nitrogen. The mixture was stirred for 4 hours at ambient temperature, the reaction mixture was purified by pouring it directly on to a column of silica and eluting with ethyl acetate/petroleum ether (9/1 followed by 10/0). The purified product was tri ed with ether and collected by filtration. The solid was dissolved in methylene chloride/methanol and 2M ethereal hydrogen chloride (1 ml) was added. The mixture was concentrated by evaporation and the precipitate was collected by filtration, washed with ether and dried under vacuum to give 4-(4-bromo-2-fluoroanilino)4-methoxy-7-(2-(2-methoxyethoxy)ethoxy)quinazoline hydrochloride (84 mg, 34%).

Workup

  1. custom(prepared
  2. customthe reaction mixture was purified
  3. additionby pouring it directly on to a column of silica
  4. washeluting with ethyl acetate/petroleum ether (9/1 followed by 10/0)
  5. filtrationcollected by filtration
  6. dissolutionThe solid was dissolved in methylene chloride/methanol
  7. addition2M ethereal hydrogen chloride (1 ml) was added
  8. concentrationThe mixture was concentrated by evaporation
  9. filtrationthe precipitate was collected by filtration
  10. washwashed with ether
  11. customdried under vacuum

Sources & evidence

ORD record
ord-669aafb7d0154d9fb2ba503ca19e01cd
Source dataset
uspto-grants-2005_05
Patent number
US06897210B2

Reaction notes

Loading…