Potassium Carbonate → HCID 22030790, compound

HRID 454178

Reaction equation

HRID 454178 reaction equation
Cl[C:2]1[C:11]2[C:6](=[CH:7][C:8]([O:14][CH2:15][CH2:16][CH2:17][N:18]3[CH2:23][CH2:22][CH2:21][CH2:20][CH2:19]3)=[C:9]([O:12][CH3:13])[CH:10]=2)[N:5]=[CH:4][N:3]=1.C(=O)([O-])[O-].[K+].[K+].[OH:30][C:31]1[CH:32]=[C:33]2[C:37](=[CH:38][CH:39]=1)[NH:36][C:35]([C:40]([OH:42])=[O:41])=[CH:34]2>CC(N(C)C)=O>[C:40]([C:35]1[NH:36][C:37]2[C:33]([CH:34]=1)=[CH:32][C:31]([O:30][C:2]1[C:11]3[C:6](=[CH:7][C:8]([O:14][CH2:15][CH2:16][CH2:17][N:18]4[CH2:23][CH2:22][CH2:21][CH2:20][CH2:19]4)=[C:9]([O:12][CH3:13])[CH:10]=3)[N:5]=[CH:4][N:3]=1)=[CH:39][CH:38]=2)([OH:42])=[O:41]

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 889585-Hydroxyindole-2-carboxylic acidHCID 110021914-Chloro-6-methoxy-7-(3-(piperidin-1-YL)propoxy)quinazoline

Product 1

HCID 22030790HCID 22030790, compoundYield 36%

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of 4-chloro-6-methoxy-7-(3-piperidinopropoxy)quinazoline (168 mg, 0.5 mmol), (prepared as described for the starting material in Example 67), potassium carbonate (345 mg, 5.0 mmol), 5-hydroxy-2-indolecarboxylic acid (106 mg, 0.6 mmol) and DMA (2.0 ml) was purged with nitrogen for 5 minutes at 25° C. This mixture was then stirred at 100° C. for 3 hours, allowed to cool to ambient temperature, filtered and the filtrate evaporated under vacuum. The residue was purified on octadecylsilane reverse phase silica eluting with acetonitrile/water/trifluoroacetic acid (as a gradient from 30/69.8/0.2 to 50/49.8/0.2) and the product further purified by silica column chromatography eluting with dichloromethane/methanolic ammonia (7M) (90/10) to give 4-(2-carboxyindol-5-yloxy)-6-methoxy-7-(3-piperidinopropoxy)quinazoline (85 mg 36%).

Workup

  1. custom(prepared
  2. customwas purged with nitrogen for 5 minutes at 25° C
  3. temperatureto cool to ambient temperature
  4. filtrationfiltered
  5. customthe filtrate evaporated under vacuum
  6. customThe residue was purified on octadecylsilane reverse phase silica eluting with acetonitrile/water/trifluoroacetic acid (as a gradient from 30/69.8/0.2 to 50/49.8/0.2) and the product
  7. customfurther purified by silica column chromatography
  8. washeluting with dichloromethane/methanolic ammonia (7M) (90/10)

Sources & evidence

ORD record
ord-9a0cb5789ada40ff9e2285c7aa4f4876
Source dataset
uspto-grants-2013_07
Patent number
US08492560B2

Linked notes

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