Triphenylphosphine → Quinazoline hydrochloride

HRID 2182543Notes

Reaction equation

HRID 2182543 reaction equation
N(C(OCC)=O)=NC(OCC)=O.N1(C/C=C/CO)CCCC1.[Cl:23]N([C:32]1[C:41]2[C:36](=[CH:37][C:38](O)=[C:39](OC)[CH:40]=2)[N:35]=[CH:34][N:33]=1)C1C=CC=CC=1F.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>C(Cl)Cl>[ClH:23].[N:35]1[C:36]2[C:41](=[CH:40][CH:39]=[CH:38][CH:37]=2)[CH:32]=[N:33][CH:34]=1

Participants

6

Reactant 4

HCID 11776TriphenylphosphineHCID 220568ethyl N-ethoxycarbonyliminocarbamateHCID 22030876(E)-4-(pyrrolidin-1-yl)but-2-en-1-olHCID 1359906824-(Chloro-2-fluoroanilino)7-hydroxy-6-methoxyquinazoline

Product 1

HCID 21186983Quinazoline hydrochlorideYield 108%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Diethyl azodicarboxylate (5.91 ml, 37 mmol) was added dropwise to a stirred mixture of (E)-4-(pyrrolidin-1-yl)but-2-en-1-ol (3.97 g, 28 mmol), 4-(chloro-2-fluoroanilino)-7-hydroxy-6-methoxyquinazoline (3.0 g, 9 mmol), (prepared as described for the starting material in Example 2), and triphenylphosphine (9.84 g, 38 mmol) in methylene chloride (300 ml). The reaction mixture was stirred for 18 hours at ambient temperature. The volatiles were removed by evaporation and the residue was purified by column chromatography eluting with methylene chloride/methanol (a gradient from 80120 to 70/30). The purified product was dissolved in methylene chloride/methanol and 1M ethereal hydrogen chloride (25 ml) was added. The precipitated product was collected by filtration, washed with ether and dried to give (E)-4-(4-chloro-2-fluoroanilino)-6-methoxy-7-(4-pyrrolidin-1-yl)but-2-en-1-yloxy)quinazoline hydrochloride (1.62 g, 33%).

Workup

  1. custom(prepared
  2. customThe volatiles were removed by evaporation
  3. customthe residue was purified by column chromatography
  4. washeluting with methylene chloride/methanol (a gradient from 80120 to 70/30)
  5. dissolutionThe purified product was dissolved in methylene chloride/methanol
  6. addition1M ethereal hydrogen chloride (25 ml) was added
  7. filtrationThe precipitated product was collected by filtration
  8. washwashed with ether
  9. customdried

Sources & evidence

ORD record
ord-e95a8a567c8c4fc6ac8c1a262c68fd8a
Source dataset
uspto-grants-2005_05
Patent number
US06897210B2

Reaction notes

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