Triphenylphosphine → (E)-4-(4-chloro-2-fluoroanilino)-6-methoxy-7-(4-morpholinobut-2-en-1-yloxy)quinazoline hydrochloride

HRID 547223Notes

Reaction equation

HRID 547223 reaction equation
N(C(OCC)=O)=NC(OCC)=O.[O:13]1[CH2:18][CH2:17][N:16]([CH2:19]/[CH:20]=[CH:21]/[CH2:22][OH:23])[CH2:15][CH2:14]1.[Cl:24][C:25]1[CH:44]=[CH:43][C:28]([NH:29][C:30]2[C:39]3[C:34](=[CH:35][C:36](O)=[C:37]([O:40][CH3:41])[CH:38]=3)[N:33]=[CH:32][N:31]=2)=[C:27]([F:45])[CH:26]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>C(Cl)Cl>[ClH:24].[Cl:24][C:25]1[CH:44]=[CH:43][C:28]([NH:29][C:30]2[C:39]3[C:34](=[CH:35][C:36]([O:23][CH2:22]/[CH:21]=[CH:20]/[CH2:19][N:16]4[CH2:17][CH2:18][O:13][CH2:14][CH2:15]4)=[C:37]([O:40][CH3:41])[CH:38]=3)[N:33]=[CH:32][N:31]=2)=[C:27]([F:45])[CH:26]=1

Participants

6

Reactant 4

HCID 11776Triphenylphosphine2×HCID 220568ethyl N-ethoxycarbonyliminocarbamate2×HCID 22478312(E)-4-morpholino-2-buten-1-ol2×HCID 1355137204-(4-Chloro-2-fluorophenylamino)-7-hydroxy-6-methoxyquinazoline

Product 1

HCID 22478303(E)-4-(4-chloro-2-fluoroanilino)-6-methoxy-7-(4-morpholinobut-2-en-1-yloxy)quinazoline hydrochlorideYield 45%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Diethyl azodicarboxylate (325 μl, 2 mmol) was added dropwise to a mixture of (E)-4-morpholinobut-2-en-1-ol (151 mg, 0.96 mmol), (J. Med. Chem. 1972, 15, 110-112), 4-(4-chloro-2-fluoroanilino)-7-hydroxy-6-methoxyquinazoline (220 mg, 0.688 mol), (prepared as described for the starting material in Example 2), and triphenylphosphine (541 mg, 2 mmol) in methylene chloride (4 ml). The mixture was stirred for 30 minutes at ambient temperature, and further (E)-4-morpholinobut-2-en-1-ol (10 mg, 0.06 mmol), triphenylphosphine (36 mg, 0.137 mol) and diethyl azodicarboxylate (22 μl, 0.14 mmol) were added. The mixture was stirred for 20 minutes and the volatiles were removed by evaporation. The residue was purified by column chromatography on silica eluting with methylene chloride/methanol (92/8). The purified solid was dissolved in methylene chloride and 2M ethereal hydrogen chloride (3 ml) was added. The volatiles were removed by evaporation and the solid was triturated with ether, collected by filtration, washed with ether and dried under vacuum to give (E)-4-(4-chloro-2-fluoroanilino)-6-methoxy-7-(4-morpholinobut-2-en-1-yloxy)quinazoline hydrochloride (165 mg, 45%).

Workup

  1. custom(prepared
  2. stirringThe mixture was stirred for 20 minutes
  3. customthe volatiles were removed by evaporation
  4. customThe residue was purified by column chromatography on silica eluting with methylene chloride/methanol (92/8)
  5. dissolutionThe purified solid was dissolved in methylene chloride
  6. addition2M ethereal hydrogen chloride (3 ml) was added
  7. customThe volatiles were removed by evaporation
  8. customthe solid was triturated with ether
  9. filtrationcollected by filtration
  10. washwashed with ether
  11. customdried under vacuum

Sources & evidence

ORD record
ord-d7ab627d32a24ef8a940c51c7761bd4e
Source dataset
uspto-grants-2011_05
Patent number
USRE042353E1

Reaction notes

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