Triphenylphosphine → HCID 22624953, compound

HRID 1737629Notes

Reaction equation

HRID 1737629 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.[N:35]1[N:36]=[CH:37][N:38]([CH2:40][CH2:41]O)[CH:39]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=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][CH2:41][CH2:40][N:38]4[CH:37]=[N:36][N:35]=[CH:39]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 11776Triphenylphosphine2×HCID 1818441,2,4-triazole, 4-(-hydroxyethyl)-2×HCID 220568ethyl N-ethoxycarbonyliminocarbamate2×HCID 1355137204-(4-Chloro-2-fluorophenylamino)-7-hydroxy-6-methoxyquinazoline

Product 1

HCID 22624953HCID 22624953, compoundYield 87.7%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Diethyl azodicarboxylate (220 μl, 1.4 mmol) was added dropwise to a solution of 4-(4-chloro-2-fluoroanilino)-7-hydroxy-6-methoxyquinazoline (150 mg, 0.47 mmol), (prepared as described for the starting material in Example 24), 2-(1,2,4-triazol-4-yl)ethanol (64 mg, 0.56 mmol) and triphenylphosphine (369 mg, 1.4 mmol) in methylene chloride (5 ml) and the mixture stirred for 30 minutes at ambient temperature. Further 2-(1,2,4-triazol-4-yl)ethanol (16 mg, 0.14 mmol), triphenylphosphine (37 mg, 0.14 mmol) and diethyl azodicarboxylate (22 μl, 0.14 mmol) was added and the mixture stirred for 1 hour at ambient temperature. The precipitated solid was collected by filtration, washed with methylene chloride and methanol and dried under vacuum. The solid was dissolved in methylene chloride/methanol and ethereal hydrogen chloride (1.5 ml of a 2.2M solution) was added. The volatiles were removed by evaporation, the solid residue was suspended in ether, collected by filtration, washed with ether and dried under vacuum to give 4-(4-chloro-2-fluoroanilino)-6-methoxy-7-(2-(1,2,4-triazol-4-yl)ethoxy)quinazoline hydrochloride (93 mg, 40%).

Workup

  1. custom(prepared
  2. stirringthe mixture stirred for 1 hour at ambient temperature
  3. filtrationThe precipitated solid was collected by filtration
  4. washwashed with methylene chloride and methanol
  5. customdried under vacuum
  6. dissolutionThe solid was dissolved in methylene chloride/methanol
  7. additionethereal hydrogen chloride (1.5 ml of a 2.2M solution) was added
  8. customThe volatiles were removed by evaporation
  9. filtrationcollected by filtration
  10. washwashed with ether
  11. customdried under vacuum

Sources & evidence

ORD record
ord-78a33a586e8a48848d0d2bbf2e5ecc2f
Source dataset
uspto-grants-1999_10
Patent number
US05962458

Reaction notes

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