Triphenylphosphine → 7-methoxy-5-(N-methylpiperidin-4-yloxy)-3-pivaloyloxymethyl-3,4-dihydroquinazolin-4-one

HRID 749188Notes

Reaction equation

HRID 749188 reaction equation
[C:1]([O:7][CH2:8][N:9]1[C:18](=[O:19])[C:17]2[C:12](=[CH:13][C:14]([O:21][CH3:22])=[CH:15][C:16]=2[OH:20])[N:11]=[CH:10]1)(=[O:6])[C:2]([CH3:5])([CH3:4])[CH3:3].O[CH:24]1[CH2:29][CH2:28][N:27]([CH3:30])[CH2:26][CH2:25]1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OC(C)(C)C)=O)=NC(OC(C)(C)C)=O>ClCCl>[C:1]([O:7][CH2:8][N:9]1[C:18](=[O:19])[C:17]2[C:12](=[CH:13][C:14]([O:21][CH3:22])=[CH:15][C:16]=2[O:20][CH:24]2[CH2:29][CH2:28][N:27]([CH3:30])[CH2:26][CH2:25]2)[N:11]=[CH:10]1)(=[O:6])[C:2]([CH3:5])([CH3:4])[CH3:3]

Participants

6

Reactant 4

HCID 11776TriphenylphosphineHCID 660484-Piperidinol, 1-methyl-HCID 97268Di-tert-butyl azodicarboxylateHCID 119745575-Hydroxy-7-methoxy-3-pivaloyloxymethyl-quinazolin-4-one

Product 1

HCID 119739027-methoxy-5-(N-methylpiperidin-4-yloxy)-3-pivaloyloxymethyl-3,4-dihydroquinazolin-4-oneYield 56.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

(5-hydroxy-7-methoxy-4-oxoquinazolin-3(4H)-yl)methyl pivalate (500 mg, 1.63 mmol), 4-hydroxy-N-methylpiperidine (280 mg, 2.45 mmol) and triphenylphosphine (640 mg, 2.45 mmol) were dissolved in anhydrous dichloromethane (8 ml), under a nitrogen atmosphere at 0° C. A solution of di-tert-butyl azodicarboxylate (560 mg, 2.45 mmol) in dichloromethane (1 ml) was added dropwise over 5 minutes and the resulting yellow solution was allowed to warm to ambient temperature and stirred for 18 hours. A further 1 equivalent of all reagents was added in the same sequence as above under the same reaction conditions and was left to stir for a further 12 hours at ambient temperature. The reaction mixture was concentrated in vacuo and the residue purified by chromatography on silica gel, eluting with 2-8% methanol in dichloromethane, to yield (7-methoxy-5-((1-methylpiperidin 4-yl)oxy)-4-oxoquinazolin-3(4H)-yl)methyl pivalate (370 mg, 56% yield) as a cream solid:

Workup

  1. customabove under the same reaction conditions
  2. waitwas left
  3. stirringto stir for a further 12 hours at ambient temperature
  4. concentrationThe reaction mixture was concentrated in vacuo
  5. customthe residue purified by chromatography on silica gel
  6. washeluting with 2-8% methanol in dichloromethane

Sources & evidence

ORD record
ord-a422a53d4fa4496f965ecd6c1783bbcd
Source dataset
uspto-grants-2008_07
Patent number
US07402585B2

Reaction notes

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