Triphenylphosphine → 4-(4-Chloro-2-fluoroanilino)-6-methoxy-7-(2-(6-methyl-2-pyridyl)ethoxy)quinazoline hydrochloride

HRID 1737624Notes

Reaction equation

HRID 1737624 reaction equation
N(C(OCC)=O)=NC(OCC)=O.[Cl: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][C:55]1[N:60]=[C:59]([CH2:61][CH2:62]O)[CH:58]=[CH:57][CH:56]=1>C(Cl)Cl>[ClH:13].[Cl: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][CH2:62][CH2:61][C:59]4[CH:58]=[CH:57][CH:56]=[C:55]([CH3:54])[N:60]=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 4

HCID 11776TriphenylphosphineHCID 702836-Methylpyridine-2-ethanolHCID 220568ethyl N-ethoxycarbonyliminocarbamateHCID 1355137204-(4-Chloro-2-fluorophenylamino)-7-hydroxy-6-methoxyquinazoline

Product 1

HCID 226250904-(4-Chloro-2-fluoroanilino)-6-methoxy-7-(2-(6-methyl-2-pyridyl)ethoxy)quinazoline hydrochlorideYield 81.6%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Diethyl azodicarboxylate (236 μl, 1.5 mmol) was added dropwise to a suspension of 4-(4-chloro-2-fluoroanilino)-7-hydroxy-6-methoxyquinazoline (160 mg, 0.5 mmol), (prepared as described for the starting material in Example 24), triphenylphosphine (393 mg, 115 mmol) and 2-(6-methyl-2-pyridyl)ethanol (96 mg, 0.7 mmol), (J. Chem. Soc. A, 1971, 388), in methylene chloride (6 ml) and the mixture stirred for 16 hours at ambient temperature. The mixture was poured directly on to a silica column and eluted with methylene chloride/methanol (95/5). The purified solid was dissolved in methylene chloride/methanol and ethereal hydrogen chloride (1.5 ml of a 4.5M solution) was added. The mixture was diluted with ether and the resulting precipitate was collected by filtration, washed with ether and dried under vacuum to give 4-(4-chloro-2-fluoroanilino)-6-methoxy-7-(2-(6-methyl-2-pyridyl)ethoxy)quinazoline hydrochloride (97 mg, 34%).

Workup

  1. custom(prepared
  2. additionThe mixture was poured directly on to a silica column
  3. washeluted with methylene chloride/methanol (95/5)
  4. dissolutionThe purified solid was dissolved in methylene chloride/methanol
  5. additionethereal hydrogen chloride (1.5 ml of a 4.5M solution) was added
  6. additionThe mixture was diluted with ether
  7. filtrationthe resulting precipitate was collected by filtration
  8. washwashed with ether
  9. customdried under vacuum

Sources & evidence

ORD record
ord-1ad0a00220494c14a52ed3858b7f1b12
Source dataset
uspto-grants-1999_10
Patent number
US05962458

Reaction notes

Loading…