Potassium Carbonate → HCID 54115576, compound

HRID 454196Notes

Reaction equation

HRID 454196 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[CH2:22][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:29][C:30]1[CH:42]=[CH:41][C:40]2[C:39]3[C:34](=[CH:35][CH:36]=[CH:37][CH:38]=3)[NH:33][C:32]=2[CH:31]=1>CN(C=O)C>[CH:31]1[C:32]2[NH:33][C:34]3[C:39](=[CH:38][CH:37]=[CH:36][CH:35]=3)[C:40]=2[CH:41]=[CH:42][C:30]=1[O:29][C:2]1[C:11]2[C:6](=[CH:7][C:8]([O:14][CH2:15][CH2:16][CH2:17][N:18]3[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

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 935512-HydroxycarbazoleHCID 111417924-Chloro-6-methoxy-7-(3-pyrrolidin-1-ylpropoxy)quinazoline

Product 1

HCID 54115576HCID 54115576, compoundYield 22%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

To a solution of 4-chloro-6-methoxy-7-(3-(pyrrolidin-1-yl)propoxy)quinazoline (100 mg, 0.31 mmol), (prepared as described for the starting material in Example 9), in DMF (10 ml) was added potassium carbonate (124 mg, 0.9 mmol, 3 eq.) followed by 2-hydroxycarbazole (66 mg, 0.36 mmol, 1.2 eq.) and the reaction heated at 100° C. for 4 hours. The DMF was removed in vacuo, the residue dissolved in dichloromethane and placed onto a 2g SCX ion-exchange column. Elution with dichloromethane, followed by 20% methanol/dichloromethane then 20% methanol/dichloromethane+3% ammonium hydroxide, gave the crude product as a brown solid. Further purification by silica bond elut chromatography eluting with dichloromethane to 15% methanol/dichloromethane+1% ammonium hydroxide, followed by trituration with ether gave 4-(9H-carbazol-2-yloxy)-6-methoxy-7-(3-(pyrrolidin-1-yl)propoxy)quinazoline (31 mg, 22%) as a white solid.

Workup

  1. customThe DMF was removed in vacuo
  2. dissolutionthe residue dissolved in dichloromethane
  3. washElution with dichloromethane
  4. custom20% methanol/dichloromethane+3% ammonium hydroxide, gave the crude product as a brown solid
  5. customFurther purification by silica bond elut chromatography
  6. washeluting with dichloromethane to 15% methanol/dichloromethane+1% ammonium hydroxide

Sources & evidence

ORD record
ord-ea62b255b094411682805dddd4ebd04d
Source dataset
uspto-grants-2013_07
Patent number
US08492560B2

Reaction notes

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