HCID 22030925, compound → HCID 22030827, compound

HRID 454081Notes

Reaction equation

HRID 454081 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH2:14][CH2:15][O:16][CH:17]1[CH2:22][CH2:21][NH:20][CH2:19][CH2:18]1)[N:9]=[CH:8][N:7]=[C:6]2[O:23][C:24]1[CH:25]=[C:26]2[C:30](=[CH:31][CH:32]=1)[NH:29][C:28]([CH3:33])=[CH:27]2>C(#N)C=C.C(Cl)Cl.CO>[C:6]([CH2:5][CH2:4][N:20]1[CH2:21][CH2:22][CH:17]([O:16][CH2:15][CH2:14][O:13][C:12]2[CH:11]=[C:10]3[C:5]([C:6]([O:23][C:24]4[CH:25]=[C:26]5[C:30](=[CH:31][CH:32]=4)[NH:29][C:28]([CH3:33])=[CH:27]5)=[N:7][CH:8]=[N:9]3)=[CH:4][C:3]=2[O:2][CH3:1])[CH2:18][CH2:19]1)#[N:7]

Participants

5

Reactant 1

HCID 22030925HCID 22030925, compound

Product 1

HCID 22030827HCID 22030827, compoundYield 171.2%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 6344DichloromethaneSolventHCID 7855AcrylonitrileSolvent

Procedure

A solution of 6-methoxy-4-(2-methylindol-5-yloxy)-7-(2-(piperidin-4-yloxy)ethoxy)quinazoline (76 mg, 0.17 mmol), (prepared as described in Example 77), in acrylonitrile (0.5 ml), methylene chloride (1 ml) and methanol (1 ml) was stirred overnight at ambient temperature. After removal of the volatiles under vacuum the residue was purified by column chromatography eluting with methylene chloride/methanol (98/2 followed by 95/5 and 90/10). The residue was triturated with ethyl acetate and ether. The resulting solid was filtered and dried under vacuum to give 7-(2-(1-(2-cyanoethyl)piperidin-4-yloxy)ethoxy)-6-methoxy-4-(2-methylindol-5-yloxy)quinazoline (73 mg, 86%).

Workup

  1. customAfter removal of the volatiles under vacuum the residue
  2. customwas purified by column chromatography
  3. washeluting with methylene chloride/methanol (98/2 followed by 95/5 and 90/10)
  4. customThe residue was triturated with ethyl acetate and ether
  5. filtrationThe resulting solid was filtered
  6. customdried under vacuum

Sources & evidence

ORD record
ord-abe1941879dd4d25a3deb7b174921283
Source dataset
uspto-grants-2013_07
Patent number
US08492560B2

Reaction notes

Loading…