Triphenylphosphine → HCID 178493968, compound

HRID 1737623Notes

Reaction equation

HRID 1737623 reaction equation
N(C(OCC)=O)=N[C:3](OCC)=[O:4].[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](OC)[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.[N:54]1[CH:59]=[CH:58][CH:57]=[C:56]([CH2:60][CH2:61]O)[CH:55]=1>C(Cl)Cl>[ClH:13].[Cl:13][C:14]1[CH:33]=[CH:32][C:17]([NH:18][C:19]2([O:4][CH3:3])[C:28]3[C:23](=[CH:24][C:25]([O:31][CH2:61][CH2:60][C:56]4[CH:55]=[N:54][CH:59]=[CH:58][CH:57]=4)=[CH:26][CH:27]=3)[N:22]=[CH:21][NH:20]2)=[C:16]([F:34])[CH:15]=1

Participants

6

Reactant 4

HCID 11776TriphenylphosphineHCID 805153-PyridineethanolHCID 220568ethyl N-ethoxycarbonyliminocarbamateHCID 1355137204-(4-Chloro-2-fluorophenylamino)-7-hydroxy-6-methoxyquinazoline

Product 1

HCID 178493968HCID 178493968, compoundYield 132.9%

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, 1.5 mmol) and 2-(3-pyridyl)ethanol (86 mg, 0.7 mmol), (J. Heterocycl. Chem. 1992, 29, 1663), in methylene chloride (6 ml) and the mixture stirred for 4 hours at ambient temperature. The mixture was poured directly on to a silica column and eluted with methylene chloride/acetonitrile/methanol (60/35/5). The purified solid was dissolved in methylene chloride/methanol and ethereal hydrogen chloride (1.5 ml of a 4.5M solution) was added. The 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)4-methoxy-7-(2-(3-pyridyl)ethoxy)quinazoline hydrochloride (154 mg, 52%).

Workup

  1. custom(prepared
  2. additionThe mixture was poured directly on to a silica column
  3. washeluted with methylene chloride/acetonitrile/methanol (60/35/5)
  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. customThe volatiles were removed by evaporation
  7. filtrationcollected by filtration
  8. washwashed with ether
  9. customdried under vacuum

Sources & evidence

ORD record
ord-664041730d394b2ca905463d62beb01d
Source dataset
uspto-grants-1999_10
Patent number
US05962458

Reaction notes

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