Triphenylphosphine → Quinazoline

HRID 2182563Notes

Reaction equation

HRID 2182563 reaction equation
N(C(OCC)=O)=NC(OCC)=O.BrC1C=CC(N[C:19]2[C:28]3[C:23](=[CH:24][C:25](O)=[C:26](OC)[CH:27]=3)[N:22]=[CH:21][N:20]=2)=C(F)C=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.CNCCCO>C(Cl)Cl>[N:22]1[C:23]2[C:28](=[CH:27][CH:26]=[CH:25][CH:24]=2)[CH:19]=[N:20][CH:21]=1

Participants

6

Reactant 4

HCID 11776TriphenylphosphineHCID 220568ethyl N-ethoxycarbonyliminocarbamateHCID 101489863-(Methylamino)-1-propanolHCID 1355038524-[(4-Bromo-2-fluorophenyl)amino]-6-methoxy-7-quinazolinol

Product 1

HCID 9210QuinazolineYield 169%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Diethyl azodicarboxylate (522 mg, 3 mmol) was added dropwise to a suspension of 4-(4-bromo-2-fluoroanilino)7-hydroxy-6-methoxyquinazoline (364 mg, 1 mmol), (prepared as described for the starting material in Example 48), triphenylphosphine (786 mg, 3 mmol) and 3-methylamino-1-propanol (178 mg, 2 mmol), (J. Am. Chem. Soc., 1954, 76, 2789), in methylene chloride (4 ml) under nitrogen. The mixture was stirred for 1 hour at ambient temperature, neutral alumina (−20 g) was added to the reaction mixture and the solvent was removed by evaporation. The powder was poured onto a column of neutral alumina and was eluted with a mixture of methylene chloride/methanol (95/5 followed by 90/10 and 80/20). The purified product was triturated with ether, collected by filtration, washed with ether and dried under vacuum to give 4-(4-bromo-2-fluoroanilino)6-methoxy-73-methylaminopropoxy)quinazoline (220 mg, 50%).

Workup

  1. custom(prepared
  2. additionneutral alumina (−20 g) was added to the reaction mixture
  3. customthe solvent was removed by evaporation
  4. additionThe powder was poured onto a column of neutral alumina
  5. washwas eluted with a mixture of methylene chloride/methanol (95/5 followed by 90/10 and 80/20)
  6. customThe purified product was triturated with ether
  7. filtrationcollected by filtration
  8. washwashed with ether
  9. customdried under vacuum

Sources & evidence

ORD record
ord-3e3eac7f98b141afb59ee54cd7093b68
Source dataset
uspto-grants-2005_05
Patent number
US06897210B2

Reaction notes

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