Triphenylphosphine → HCID 18753425, compound

HRID 547215Notes

Reaction equation

HRID 547215 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.[CH3:35][C@H:36]1[CH2:41][N:40]([CH2:42][CH2:43][CH2:44]O)[CH2:39][C@@H:38]([CH3:46])[O:37]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][CH2:44][CH2:43][CH2:42][N:40]4[CH2:39][CH:38]([CH3:46])[O:37][CH:36]([CH3:35])[CH2:41]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 11776TriphenylphosphineHCID 220568ethyl N-ethoxycarbonyliminocarbamateHCID 532160581280565-71-0HCID 1355137204-(4-Chloro-2-fluorophenylamino)-7-hydroxy-6-methoxyquinazoline

Product 1

HCID 18753425HCID 18753425, compoundYield 590%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Diethyl azodicarboxylate (209 mg, 1 mmol) was added dropwise to a mixture of 4-(4-chloro-2-fluoroanilino)-7-hydroxy-6-methoxyquinazoline (128 mg, 0.4 mmol), (prepared as described for the starting material in Example 2), cis-3-(2,6-dimethylmorpholino)-1-propanol (97 mg, 0.56 mmol) and triphenylphosphine (314 mg, 1.2 mmol) in methylene chloride (4 ml) under nitrogen. The mixture was stirred for 1 hour at ambient temperature and the solvent was removed by evaporation. The residue was purified by column chromatography eluting with methylene chloride/methanol (95/5 followed by 90/10). The purified product was dissolved in methylene chloride and 2M ethereal hydrogen chloride (1 ml) was added. The solution was diluted with ether and left to stand. The resulting precipitate was collected by filtration, washed with ether and dried under vacuum to give 4-(4-chloro-2-fluoroanilino)-7-(3-(2,6dimethylmorpholino)propoxy)-6-methoxyquinazoline hydrochloride (130 mg, 590%).

Workup

  1. custom(prepared
  2. customthe solvent was removed by evaporation
  3. customThe residue was purified by column chromatography
  4. washeluting with methylene chloride/methanol (95/5 followed by 90/10)
  5. dissolutionThe purified product was dissolved in methylene chloride
  6. addition2M ethereal hydrogen chloride (1 ml) was added
  7. additionThe solution was diluted with ether
  8. waitleft
  9. filtrationThe resulting precipitate was collected by filtration
  10. washwashed with ether
  11. customdried under vacuum

Sources & evidence

ORD record
ord-49e30d3d6c13445e922068dd39601316
Source dataset
uspto-grants-2011_05
Patent number
USRE042353E1

Reaction notes

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