Dimethylformamide → HCID 54003210, compound

HRID 454212Notes

Reaction equation

HRID 454212 reaction equation
Cl[C:2]1[C:11]2[C:6](=[CH:7][C:8]([O:14][CH2:15][CH:16]3[CH2:21][CH2:20][N:19](CC#N)[CH2:18][CH2:17]3)=[C:9]([O:12][CH3:13])[CH:10]=2)[N:5]=[CH:4][N:3]=1.[OH:25][C:26]1[CH:27]=[C:28]2[C:32](=[CH:33][CH:34]=1)[NH:31][CH:30]=[CH:29]2.[C:35](=O)([O-])[O-].[Cs+].[Cs+].C[N:42]([CH:44]=O)C>>[C:44]([CH2:35][CH:15]([CH:16]1[CH2:17][CH2:18][NH:19][CH2:20][CH2:21]1)[O:14][C:8]1[CH:7]=[C:6]2[C:11]([C:2]([O:25][C:26]3[CH:27]=[C:28]4[C:32](=[CH:33][CH:34]=3)[NH:31][CH:30]=[CH:29]4)=[N:3][CH:4]=[N:5]2)=[CH:10][C:9]=1[O:12][CH3:13])#[N:42]

Participants

5

Reactant 4

HCID 6228DimethylformamideHCID 10796Cesium carbonateHCID 160545-HydroxyindoleHCID 22030907HCID 22030907, compound

Product 1

HCID 54003210HCID 54003210, compoundYield 17%

Conditions

Temperature
90 °C

Procedure

A solution of 4-chloro-6-methoxy-7-((1-cyanomethylpiperidin-4-yl)methoxy)quinazoline (200 mg, 0.58 mmol) and 5-hydroxyindole (85 mg, 0.63 mmol) in DMF (3 ml) containing cesium carbonate (282 mg, 0.86 mmol) was stirred at 90° C. for 90 minutes. After cooling, the mixture was poured onto water (25 ml). The precipitate was filtered, dried under vacuum and purified by reverse phase column chromatography on silica (Kromasil® C18) eluting with methanol/water (1% acetic acid) (1/1). The fractions containing the expected product were combined and evaporated to give 7-((1-cyanomethyl)piperidin-4-ylmethoxy)-4-(indol-5-yloxy)-6-methoxyquinazoline (44 mg, 17%).

Workup

  1. temperatureAfter cooling
  2. additionthe mixture was poured onto water (25 ml)
  3. filtrationThe precipitate was filtered
  4. customdried under vacuum
  5. custompurified by reverse phase column chromatography on silica (Kromasil® C18)
  6. washeluting with methanol/water (1% acetic acid) (1/1)
  7. additionThe fractions containing the expected product
  8. customevaporated

Sources & evidence

ORD record
ord-82f661d328cc4a6eb3ca6f1d3a9b62a1
Source dataset
uspto-grants-2013_07
Patent number
US08492560B2

Reaction notes

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