Potassium Carbonate → 4-(7-Azaindol-5-yloxy)-6-methoxy-7-(3-(4-methylsulphonylpiperazin-1-yl)propoxy)quinazoline

HRID 2068038Notes

Reaction equation

HRID 2068038 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][N:21]([S:24]([CH3:27])(=[O:26])=[O:25])[CH2:20][CH2:19]3)=[C:9]([O:12][CH3:13])[CH:10]=2)[N:5]=[CH:4][N:3]=1.[OH:28][C:29]1[CH:30]=[C:31]2[C:35](=[N:36][CH:37]=1)[NH:34][CH:33]=[CH:32]2.C(=O)([O-])[O-].[K+].[K+]>CN(C=O)C>[NH:34]1[C:35]2[C:31](=[CH:30][C:29]([O:28][C:2]3[C:11]4[C:6](=[CH:7][C:8]([O:14][CH2:15][CH2:16][CH2:17][N:18]5[CH2:23][CH2:22][N:21]([S:24]([CH3:27])(=[O:26])=[O:25])[CH2:20][CH2:19]5)=[C:9]([O:12][CH3:13])[CH:10]=4)[N:5]=[CH:4][N:3]=3)=[CH:37][N:36]=2)[CH:32]=[CH:33]1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 220307221H-Pyrrolo[2,3-b]pyridin-5-olHCID 866180984-Chloro-6-methoxy-7-(3-(4-methylsulphonylpiperazin-1-yl)propoxy)quinazoline

Product 1

HCID 101745984-(7-Azaindol-5-yloxy)-6-methoxy-7-(3-(4-methylsulphonylpiperazin-1-yl)propoxy)quinazolineYield 45%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
85 °C

Procedure

A suspension of 4-chloro-6-methoxy-7-(3-(4-methylsulphonylpiperazin-1-yl)propoxy)quinazoline (0.25 g, 0.66 mmol), 5-hydroxy-7-azaindole (0.089 g, 0.663 mmol), (prepared as described for the starting material in Example 2), and potassium carbonate (0.091 g, 0.66 mmol) in DMF (3 ml) was stirred at 85° C. for 3 hours. The mixture was filtered and the filtrate was purified by preparative LCtMS eluting with acetonitrile/water (containing 1% acetic acid). The fractions containing the expected product were combined and evaporated. The residue was dissolved in methylene chloride and washed with 0.5N aqueous ammonia followed by brine, dried (MgSO4) and evaporated. The residue was triturated under diethyl ether, filtered and dried under vacuum to give 4-(7-azaindol-5-yloxy)-6-methoxy-7-(3-(4-methylsulphonylpiperazin-1-yl)propoxy)quinazoline (0.138 g, 45%).

Workup

  1. custom(prepared
  2. filtrationThe mixture was filtered
  3. customthe filtrate was purified by preparative LCtMS
  4. washeluting with acetonitrile/water (containing 1% acetic acid)
  5. additionThe fractions containing the expected product
  6. customevaporated
  7. dissolutionThe residue was dissolved in methylene chloride
  8. washwashed with 0.5N aqueous ammonia
  9. dry with materialdried (MgSO4)
  10. customevaporated
  11. customThe residue was triturated under diethyl ether
  12. filtrationfiltered
  13. customdried under vacuum

Sources & evidence

ORD record
ord-0f84e3198ab94000a7e0e2a4df767612
Source dataset
uspto-grants-2012_10
Patent number
US08293902B2

Reaction notes

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