Potassium Carbonate → Quinazoline

HRID 1791721Notes

Reaction equation

Cl[C:2]1[C:11]2[C:6](=[CH:7][C:8](OCCCN3CCCC3)=[C:9](OC)[CH:10]=2)[N:5]=[CH:4][N:3]=1.C(=O)([O-])[O-].[K+].[K+].OC1C=CC2C3C(=CC=CC=3)NC=2C=1>CN(C=O)C>[N:5]1[C:6]2[C:11](=[CH:10][CH:9]=[CH:8][CH:7]=2)[CH:2]=[N:3][CH:4]=1

Participants

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, 3eq.) followed by 2-hydroxycarbazole (66 mg, 0.36 mmol, 1.2eq.) 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 2 g 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

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

Sources & evidence

ORD record: ord-08221d9b796a49a8a40abe09d42df29c
Source dataset: uspto-grants-2006_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07074800B1

Reaction notes

Loading…