Dichloromethane → HCID 22478225, compound

HRID 1838607Notes

Reaction equation

HRID 1838607 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.[O:54]1[CH2:59][CH2:58][N:57]([CH2:60][CH2:61][O:62][CH2:63][CH2:64]O)[CH2:56][CH2:55]1.C(Cl)[Cl:67]>>[ClH:67].[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][CH2:64][CH2:63][O:62][CH2:61][CH2:60][N:57]4[CH2:58][CH2:59][O:54][CH2:55][CH2:56]4)=[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 11776TriphenylphosphineHCID 220568ethyl N-ethoxycarbonyliminocarbamateHCID 4584644-(2-(2-Hydroxyethoxy)ethyl)morpholineHCID 1355038524-[(4-Bromo-2-fluorophenyl)amino]-6-methoxy-7-quinazolinol

Product 1

HCID 22478225HCID 22478225, compoundYield 49%

Procedure

Diethyl azodicarboxylate (378 μl, 2.4 mmol) was added dropwise to a mixture of 4-(4-bromo-2-fluoroanilino)-7-hydroxy-6-methoxyquinazoline (292 mg, 0.8 mmol), (prepared as described for the starting material in Example 48), triphenylphosphine (629 mg, 2.4 mmol) and 2-(2-morpholinoethoxy)ethanol (196 mg, 1.12 mmol), (prepared as described for the starting material in Example 53), in methylene chloride (10 ml) under nitrogen. The mixture was stirred for 3.5 hours at ambient temperature and the mixture was purified by pouring it directly on to a column of silica and eluting with methylene chloride/acetonitrile/methanol (6/3/1). The purified product was dissolved in methylene chloride/methanol and the insolubles were removed by filtration. 2M Ethereal hydrogen chloride (1 ml) was added to the filtrate and the volatiles were removed by evaporation. The residue was triturated with ether, collected by filtration, washed with ether and dried under vacuum to give 4-(4-bromo-2-fluoroanilino)-6-methoxy-7-(2-(2-morpholinoethoxy)ethoxy)quinazoline hydrochloride (232 mg, 49%).

Workup

  1. custom(prepared
  2. custom(prepared
  3. customthe mixture was purified
  4. additionby pouring it directly on to a column of silica
  5. washeluting with methylene chloride/acetonitrile/methanol (6/3/1)
  6. dissolutionThe purified product was dissolved in methylene chloride/methanol
  7. customthe insolubles were removed by filtration
  8. addition2M Ethereal hydrogen chloride (1 ml) was added to the filtrate
  9. customthe volatiles were removed by evaporation
  10. customThe residue was triturated with ether
  11. filtrationcollected by filtration
  12. washwashed with ether
  13. customdried under vacuum

Sources & evidence

ORD record
ord-ffdc6fc9d83e467e930337c1d635bdfb
Source dataset
uspto-grants-2004_01
Patent number
US06673803B2

Reaction notes

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