Dichloromethane → HCID 18753482, compound

HRID 547225Notes

Reaction equation

HRID 547225 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[CH2:55][CH2:56][N:57]1[CH2:61][CH2:60][CH2:59][C:58]1=[O:62].C(Cl)[Cl:64]>>[ClH:64].[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][CH2:55][CH2:56][N:57]4[CH2:61][CH2:60][CH2:59][C:58]4=[O:62])=[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 769801-(2-Hydroxyethyl)-2-pyrrolidinoneHCID 220568ethyl N-ethoxycarbonyliminocarbamateHCID 1355038524-[(4-Bromo-2-fluorophenyl)amino]-6-methoxy-7-quinazolinol

Product 1

HCID 18753482HCID 18753482, compoundYield 60%

Procedure

Diethyl azodicarboxylate (283 μl, 1.8 mmol) was added dropwise to a mixture of 4-(4-bromo-2-fluoroanilino)-7-hydroxy-6-methoxyquinazoline (218 mg, 0.6 mmol), (prepared as described for the starting material in Example 48), triphenylphosphine (95 μl, 0.84 mmol) and 1-(2-hydroxyethyl)-2-pyrrolidinone (95 μl, 0.84 mmol) in methylene chloride (8 ml) under nitrogen. The mixture was stirred for 4 hours at ambient temperature, and then purified by pouring it directly on to a column of silica and eluting with methylene chloride/acetonitrile/methanol (60/32.5/7.5). The purified product was triturated with ether and collected by filtration. The solid was dissolved in methylene chloride/methanol (1/1) and 2M ethereal hydrogen chloride (1 ml) was added. The volatiles were removed by evaporation, the residue was triturated with ether, collected by filtration and dried under vacuum to give 4-(4-bromo-2-fluoroanilino)-6-methoxy-7-(2-(2-oxopyrrolidin-1-yl)ethoxy)quinazoline hydrochloride (182 mg, 60%).

Workup

  1. custom(prepared
  2. custompurified
  3. additionby pouring it directly on to a column of silica
  4. washeluting with methylene chloride/acetonitrile/methanol (60/32.5/7.5)
  5. customThe purified product was triturated with ether
  6. filtrationcollected by filtration
  7. dissolutionThe solid was dissolved in methylene chloride/methanol (1/1)
  8. addition2M ethereal hydrogen chloride (1 ml) was added
  9. customThe volatiles were removed by evaporation
  10. customthe residue was triturated with ether
  11. filtrationcollected by filtration
  12. customdried under vacuum

Sources & evidence

ORD record
ord-937b7619a78d480e891f2addacdb0a87
Source dataset
uspto-grants-2011_05
Patent number
USRE042353E1

Reaction notes

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