Triphenylphosphine → 2-{2-[3-(Isopropylcarbamoylmethyl)-2-(3-methoxyphenyl)-4-oxo-3,4-dihydroquinazolin-6-yloxy]ethyl}piperidine-1-carboxylic acid tert-butyl ester

HRID 1157474Notes

Reaction equation

HRID 1157474 reaction equation
[OH:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]=[C:7]([C:12]1[CH:17]=[CH:16][CH:15]=[C:14]([O:18][CH3:19])[CH:13]=1)[N:6]([CH2:20][C:21]([NH:23][CH:24]([CH3:26])[CH3:25])=[O:22])[C:5]2=[O:27].[C:28]([N:35]1[CH2:40][CH2:39][CH2:38][CH2:37][CH:36]1[CH2:41][CH2:42]O)([O:30][C:31]([CH3:34])([CH3:33])[CH3:32])=[O:29].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.CC(OC(/N=N/C(OC(C)C)=O)=O)C>ClCCl.CN(C=O)C>[C:31]([O:30][C:28]([N:35]1[CH2:40][CH2:39][CH2:38][CH2:37][CH:36]1[CH2:41][CH2:42][O:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]=[C:7]([C:12]1[CH:17]=[CH:16][CH:15]=[C:14]([O:18][CH3:19])[CH:13]=1)[N:6]([CH2:20][C:21](=[O:22])[NH:23][CH:24]([CH3:25])[CH3:26])[C:5]2=[O:27])=[O:29])([CH3:34])([CH3:33])[CH3:32]

Participants

7

Reactant 4

HCID 11776TriphenylphosphineHCID 5103438Tert-butyl 2-(2-hydroxyethyl)piperidine-1-carboxylateHCID 5363146Diisopropyl azodicarboxylateHCID 685249242-[6-hydroxy-2-(3-methoxyphenyl)-4-oxo-4H-quinazolin-3-yl]-N-isopropylacetamide

Product 1

HCID 595117982-{2-[3-(Isopropylcarbamoylmethyl)-2-(3-methoxyphenyl)-4-oxo-3,4-dihydroquinazolin-6-yloxy]ethyl}piperidine-1-carboxylic acid tert-butyl esterYield 20%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

A mixture of 2-[6-hydroxy-2-(3-methoxy-phenyl)-4-oxo-4H-quinazolin-3-yl]-N-isopropyl-acetamide (INTERMEDIATE IV.4) (200 mg, 0.55 mmol), N-Boc-2-piperidine ethanol (250 mg, 1.09 mmol) and resin-bound triphenylphosphine (˜3 mmol/g, 543 mg, 1.63 mmol) in dichloromethane (4.5 mL) and DMF (0.5 mL) was cooled to 0° C. and diisopropylazodicarboxylate (DIAD) (0.21 mL, 1.09 mmol) was added dropwise with stirring. The reaction mixture was allowed to warm to room temperature and stirring was continued for 16 h. The mixture was then filtered and concentrated in vacuo. The crude residue was dissolved in dichloromethane (100 mL) and washed with 1 N NaOH (aq.) and brine. The organic phase was dried (MgSO4), filtered and concentrated in vacuo. Purification by chromatography on silica gel with ethyl acetate:hexane (2:1, v/v) afforded 2-{2-[3-(isopropylcarbamoylmethyl)-2-(3-methoxyphenyl)-4-oxo-3,4-dihydroquinazolin-6-yloxy]ethyl}piperidine-1-carboxylic acid tert-butyl ester (65 mg, 0.11 mmol, 20%).

Workup

  1. temperatureto warm to room temperature
  2. stirringstirring
  3. filtrationThe mixture was then filtered
  4. concentrationconcentrated in vacuo
  5. dissolutionThe crude residue was dissolved in dichloromethane (100 mL)
  6. washwashed with 1 N NaOH (aq.) and brine
  7. dry with materialThe organic phase was dried (MgSO4)
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customPurification by chromatography on silica gel with ethyl acetate:hexane (2:1

Sources & evidence

ORD record
ord-b0e6f0499b024eb8b0ee924047ecea08
Source dataset
uspto-grants-2010_10
Patent number
US07807686B2

Reaction notes

Loading…