Dichloromethane → HCID 18753484, compound

HRID 2227974Notes

Reaction equation

HRID 2227974 reaction equation
N(C(OCC)=O)=NC(OCC)=O.[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]([O:29][CH3:30])[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[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])=[C:26]([O:29][CH3:30])[CH:27]=3)[N:22]=[CH:21][N: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 18753484HCID 18753484, 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 triturated 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)-6-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. customThe purified product was triturated with ether
  6. filtrationcollected by filtration
  7. dissolutionThe solid was dissolved in methylene chloride/methanol
  8. addition2M ethereal hydrogen chloride (1 ml) was added
  9. concentrationThe mixture was concentrated by evaporation
  10. filtrationthe precipitate was collected by filtration
  11. washwashed with ether
  12. customdried under vacuum

Sources & evidence

ORD record
ord-dc866f0e5425454da2f7ddd1d132a77f
Source dataset
uspto-grants-2002_07
Patent number
US06414148B1

Reaction notes

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