Triphenylphosphine → HCID 18474778, compound

HRID 547227Notes

Reaction equation

HRID 547227 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.O[CH2:36][CH2:37][CH2:38][N:39]1[C:44](=[O:45])[CH2:43][O:42][CH2:41][C:40]1=[O:46].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][CH2:36][CH2:37][CH2:38][N:39]4[C:44](=[O:45])[CH2:43][O:42][CH2:41][C:40]4=[O:46])=[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 11776TriphenylphosphineHCID 220568ethyl N-ethoxycarbonyliminocarbamateHCID 22478308HCID 22478308, compoundHCID 1355137204-(4-Chloro-2-fluorophenylamino)-7-hydroxy-6-methoxyquinazoline

Product 1

HCID 18474778HCID 18474778, compoundYield 18.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Diethyl azodicarboxylate (567 μl, 3.6 mmol) was added dropwise to a mixture of 4-(4-chloro-2-fluoroanilino)-7-hydroxy-6-methoxyquinazoline (383 mg, 1.2 mmol), (prepared as described for the starting material in Example 2), 4-(3-hydroxypropyl)-3,5-dioxomorpholine (291 mg, 1.68 mmol) and triphenylphosphine (944 mg, 3.6 mmol) in methylene chloride (10 ml) under nitrogen. The mixture was sired at ambient temperature for 6 hours and the insolubles were removed by filtration. The filtrate was purified by pouring it directly on to a column of silica and eluting with methylene chloride/acetonitrile/methanol (60/34/6 followed by 60/24/16 and 60/16/24). The semi-purified product was repurified by column chromatography eluting with methylene chloride/acetonitrile/methanol (5/4/1). The purified product was dissolved in methylene chloride/methanol 2M ethereal hydrogen chloride (1 ml) was added and the volatiles were removed by evaporation. The residue was triturated with ether, collected by filtration, washed with ether and dried under vacuum to give 4-(4-chloro-2-fluoroanilino)-7-(3-(3,5-dioxomorpholino)propoxy)-6-methoxyquinazoline hydrochloride (56 mg, 10%).

Workup

  1. custom(prepared
  2. customthe insolubles were removed by filtration
  3. customThe filtrate was purified
  4. additionby pouring it directly on to a column of silica
  5. washeluting with methylene chloride/acetonitrile/methanol (60/34/6 followed by 60/24/16 and 60/16/24)
  6. customThe semi-purified product was repurified by column chromatography
  7. washeluting with methylene chloride/acetonitrile/methanol (5/4/1)
  8. dissolutionThe purified product was dissolved in methylene chloride/methanol 2M ethereal hydrogen chloride (1 ml)
  9. additionwas added
  10. customthe volatiles were removed by evaporation
  11. customThe residue was triturated with ether
  12. filtrationcollected by filtration
  13. washwashed with ether
  14. customdried under vacuum

Sources & evidence

ORD record
ord-1f00922ad9bf4690823cfbb5ba0d3d97
Source dataset
uspto-grants-2011_05
Patent number
USRE042353E1

Reaction notes

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