Triphenylphosphine → 4-(4-chloro-2-fluoroanilino)-7-(2-(N-(2,6-dimethyl-4-pyridyl)-N-methylamino)ethoxy)-6-methoxyquinazoline

HRID 1737540Notes

Reaction equation

HRID 1737540 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[CH:60]=[C:59]([N:61]([CH2:63][CH2:64]O)[CH3:62])[CH:58]=[C:57]([CH3:66])[N:56]=1.[O-2].[Al+3].[O-2].[O-2].[Al+3]>C(Cl)Cl.CO>[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][CH2:64][CH2:63][N:61]([C:59]4[CH:58]=[C:57]([CH3:66])[N:56]=[C:55]([CH3:54])[CH:60]=4)[CH3:62])=[C:26]([O:29][CH3:30])[CH:27]=3)[N:22]=[CH:21][N:20]=2)=[C:16]([F:34])[CH:15]=1

Participants

8

Reactant 5

HCID 11776TriphenylphosphineHCID 220568ethyl N-ethoxycarbonyliminocarbamateHCID 9989226AluminaHCID 226250732-(N-(2,6-dimethyl-4-pyridyl)-N-methylamino)ethanolHCID 1355137204-(4-Chloro-2-fluorophenylamino)-7-hydroxy-6-methoxyquinazoline

Product 1

HCID 226249914-(4-chloro-2-fluoroanilino)-7-(2-(N-(2,6-dimethyl-4-pyridyl)-N-methylamino)ethoxy)-6-methoxyquinazolineYield 70.5%

Reagents, catalysts & solvents 2

HCID 887MethanolCatalystHCID 6344DichloromethaneSolvent

Procedure

Diethyl azodicarboxylate (261 mg, 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, 1.5 mmol) and 2-(N-(2,6-dimethyl-4-pyridyl)-N-methylamino)ethanol (125 mg, 0.7 mmol) in methylene chloride (5 ml) and the mixture stirred for 2 hours at ambient temperature. Methanol (10 drops) was added and the mixture was poured on to a column of neutral aluminium oxide and the product was separated by elution with methylene chloride/acetonitrile/methanol (60/35/35). The purified solid product was triturated with ether and collected by filtration. The solid was dissolved in methylene chloride/methanol and a solution of 3M ethereal hydrogen chloride (1 ml) was added. The solid was collected by filtration, washed with ether and dried under vacuum to give 4-(4-chloro-2-fluoroanilino)-7-(2-(N-(2,6-dimethyl-4-pyridyl)-N-methylamino)ethoxy)-6-methoxyquinazoline (170 mg, 61%).

Workup

  1. custom(prepared
  2. customthe product was separated by elution with methylene chloride/acetonitrile/methanol (60/35/35)
  3. customThe purified solid product was triturated with ether
  4. filtrationcollected by filtration
  5. dissolutionThe solid was dissolved in methylene chloride/methanol
  6. additiona solution of 3M ethereal hydrogen chloride (1 ml) was added
  7. filtrationThe solid was collected by filtration
  8. washwashed with ether
  9. customdried under vacuum

Sources & evidence

ORD record
ord-dc6d6a354fe844c1b901fa599344ac51
Source dataset
uspto-grants-1999_10
Patent number
US05962458

Reaction notes

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