Triphenylphosphine → HCID 22624953, compound

HRID 1384678Notes

Reaction equation

HRID 1384678 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%). 1H NMR Spectrum: (DMSOd6; CF3COOD) 4.02(s, 3H); 4.66(t, 2H); 4.85(t, 2H); 7.41(s, 1H); 7.46(dd, 1H); 7.62(t, 1H); 7.69(dd, 1H); 8.11(s, 1H); 8.89(s, 1H); 9.55 (s, 2H) MS-ESI: 415 [MH]+

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-73ff32da2f8a4ba79613612af29b7e96
Source dataset
uspto-grants-2001_07
Patent number
US06258951B1

Reaction notes

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