Ammonia → HCID 136340782, compound

HRID 1372995Notes

Reaction equation

HRID 1372995 reaction equation
[Cl:1][C:2]1[C:11]2[C:6](=[C:7]([NH:28][C:29]3[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=3)[C:8]([O:15][CH2:16][CH:17]([O:24]C(=O)C)[CH2:18][N:19]3[CH2:23][CH2:22][CH2:21][CH2:20]3)=[C:9]([O:13][CH3:14])[C:10]=2[OH:12])[N:5]=[C:4]([F:35])[N:3]=1.N>CO>[Cl:1][C:2]1[C:11]2[C:6](=[C:7]([NH:28][C:29]3[CH:30]=[CH:31][CH:32]=[CH:33][CH:34]=3)[C:8]([O:15][CH2:16][CH:17]([OH:24])[CH2:18][N:19]3[CH2:23][CH2:22][CH2:21][CH2:20]3)=[C:9]([O:13][CH3:14])[C:10]=2[OH:12])[N:5]=[C:4]([F:35])[N:3]=1

Participants

4

Reactant 2

HCID 222AmmoniaHCID 136340829HCID 136340829, compound

Product 1

HCID 136340782HCID 136340782, compoundYield 12.8%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A suspension of 4-chloro-2-fluoro-5-hydroxyphenylamino-7-[2-acetoxy-3-(pyrrolidin-1-yl)propoxy]-6-methoxyquinazoline (170 mg) in methanol saturated with ammonia (6 ml) was stirred at ambient temperature for 2 hours. The volatiles were removed under vacuum. The residue was partitioned between ethyl acetate and water. The pH of the aqueous layer was adjusted to 6.5. The organic layer was separated, washed with water, dried (MgSO4) and evaporated. The residue was triturated under diethyl ether, filtered, washed with ether and dried under vacuum to give 4-chloro-2-fluoro-5-hydroxyphenylamino-7-[2-hydroxy-3-(pyrrolidin-1-yl)propoxy]-6-methoxyquinazoline (20 mg).

Workup

  1. customThe volatiles were removed under vacuum
  2. customThe residue was partitioned between ethyl acetate and water
  3. customThe organic layer was separated
  4. washwashed with water
  5. dry with materialdried (MgSO4)
  6. customevaporated
  7. customThe residue was triturated under diethyl ether
  8. filtrationfiltered
  9. washwashed with ether
  10. customdried under vacuum

Sources & evidence

ORD record
ord-1e765c48aeb640609d209a28e830455e
Source dataset
uspto-grants-2007_01
Patent number
US07160889B2

Reaction notes

Loading…