Potassium Carbonate → 7-{[1-(tert-butoxycarbonyl)piperidin-4-yl]methoxy}-6-methoxy-4-[(3-methyl-1H-indol-5-yl)oxy]quinazoline

HRID 1668673Notes

Reaction equation

HRID 1668673 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([CH2:14][O:15][C:16]2[CH:25]=[C:24]3[C:19]([C:20](Cl)=[N:21][CH:22]=[N:23]3)=[CH:18][C:17]=2[O:27][CH3:28])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[OH:29][C:30]1[CH:31]=[C:32]2[C:36](=[CH:37][CH:38]=1)[NH:35][CH:34]=[C:33]2[CH3:39].C(=O)([O-])[O-].[K+].[K+]>CN(C=O)C>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([CH2:14][O:15][C:16]2[CH:25]=[C:24]3[C:19]([C:20]([O:29][C:30]4[CH:31]=[C:32]5[C:36](=[CH:37][CH:38]=4)[NH:35][CH:34]=[C:33]5[CH3:39])=[N:21][CH:22]=[N:23]3)=[CH:18][C:17]=2[O:27][CH3:28])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 1927343-methyl-1H-indol-5-olHCID 219360467-(N-tert-butoxycarbonylpiperidin-4-ylmethoxy)-4-chloro-6-methoxyquinazoline

Product 1

HCID 220305997-{[1-(tert-butoxycarbonyl)piperidin-4-yl]methoxy}-6-methoxy-4-[(3-methyl-1H-indol-5-yl)oxy]quinazolineYield 99.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
90 °C

Procedure

A mixture of 7-{[1-(tert-butoxycarbonyl)piperidin-4-yl]methoxy}-4-chloro-6-methoxyquinazoline (4.6 g), 5-hydroxy-3-methylindole (2 g), (Journal of Organic Chemistry 1993, 58, 3757), potassium carbonate (3.1 g) and DMF (20 ml) was stirred and heated to 90° C. for 2 hours. The solid was removed by filtration washed with acetonitrile and the combined filtrates concentrated to dryness under vacuum. The product so obtained was triturated under ether/petroleum ether (8/2), collected by filtration and dried to give 7-{[1-(tert-butoxycarbonyl)piperidin-4-yl]methoxy}-6-methoxy-4-[(3-methyl-1H-indol-5-yl)oxy]quinazoline (5.8 g).

Workup

  1. customThe solid was removed by filtration
  2. washwashed with acetonitrile
  3. concentrationthe combined filtrates concentrated to dryness under vacuum
  4. customThe product so obtained
  5. customwas triturated under ether/petroleum ether (8/2)
  6. filtrationcollected by filtration
  7. customdried

Sources & evidence

ORD record
ord-8a4ab405018a40e089e54074614fd02c
Source dataset
uspto-grants-2011_08
Patent number
US07989460B2

Reaction notes

Loading…