Triphenylphosphine → 6-Methoxy-3-((pivaloyloxy)methyl)-7-(2-(pyrrolidin-1-yl)ethoxy)-3,4-dihydroquinazolin-4-one

HRID 1386307Notes

Reaction equation

HRID 1386307 reaction equation
N(C(OCC)=O)=NC(OCC)=O.[OH:13][C:14]1[CH:23]=[C:22]2[C:17]([C:18](=[O:32])[N:19]([CH2:24][O:25][C:26](=[O:31])[C:27]([CH3:30])([CH3:29])[CH3:28])[CH:20]=[N:21]2)=[CH:16][C:15]=1[O:33][CH3:34].O[CH2:36][CH2:37][N:38]1[CH2:42][CH2:41][CH2:40][CH2:39]1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>C(Cl)Cl>[CH3:34][O:33][C:15]1[CH:16]=[C:17]2[C:22](=[CH:23][C:14]=1[O:13][CH2:36][CH2:37][N:38]1[CH2:42][CH2:41][CH2:40][CH2:39]1)[N:21]=[CH:20][N:19]([CH2:24][O:25][C:26](=[O:31])[C:27]([CH3:28])([CH3:29])[CH3:30])[C:18]2=[O:32]

Participants

6

Reactant 4

HCID 11776Triphenylphosphine2×HCID 762881-PyrrolidineethanolHCID 220568ethyl N-ethoxycarbonyliminocarbamate2×HCID 10804576(7-Hydroxy-6-methoxy-4-oxoquinazolin-3(4H)-yl)methyl pivalate

Product 1

HCID 217172866-Methoxy-3-((pivaloyloxy)methyl)-7-(2-(pyrrolidin-1-yl)ethoxy)-3,4-dihydroquinazolin-4-oneYield 55%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Diethyl azodicarboxylate (566 mg, 3.25 mmol) was added dropwise to a solution of 7-hydroxy-6-methoxy-3-((pivaloyloxy)methyl)-3,4-dihydroquinazolin-4-one (765 mg, 2.5 mmol), (prepared as described for the starting material in Example 22), 1-(2-hydroxyethyl)pyrrolidine (374 mg, 3.25 mmol) and triphenylphosphine (851 mg, 3.25 mmol) in methylene chloride (15 ml). The mixture was stirred for 1 hour at ambient temperature and further triphenylphosphine (861 mg, 3.25 mmol) followed by diethyl azodicarboxylate (566 mg, 3.25 mmol) was added. The mixture was stirred for 1 hour at ambient temperature and the solvent was removed by evaporation. The residue was dissolved in ethyl acetate/ether and extracted with 2M hydrochloric acid. The aqueous layer was basified by addition of solid sodium hydrogen carbonate and extracted with methylene chloride. The combined extracts were dried (MgSO4), and the solvent removed by evaporation. The resulting oil was purified by column chromatography on neutral aluminium oxide eluting with methylene chloride/methanol (90/10 followed by 80/20) to give 6-methoxy-3-((pivaloyloxy)methyl)-7-(2-(pyrrolidin-1-yl)ethoxy)-3,4-dihydroquinazolin-4-one (550 mg, 55%).

Workup

  1. custom(prepared
  2. additionwas added
  3. stirringThe mixture was stirred for 1 hour at ambient temperature
  4. customthe solvent was removed by evaporation
  5. dissolutionThe residue was dissolved in ethyl acetate/ether
  6. extractionextracted with 2M hydrochloric acid
  7. additionThe aqueous layer was basified by addition of solid sodium hydrogen carbonate
  8. extractionextracted with methylene chloride
  9. dry with materialThe combined extracts were dried (MgSO4)
  10. customthe solvent removed by evaporation
  11. customThe resulting oil was purified by column chromatography on neutral aluminium oxide eluting with methylene chloride/methanol (90/10 followed by 80/20)

Sources & evidence

ORD record
ord-6579063e592741468f32cfc4480bfbe2
Source dataset
uspto-grants-2001_07
Patent number
US06265411B1

Reaction notes

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