Methanol → N-{3-[5-(2-fluoro-4-iodophenylamino)-6,8-dimethyl-2,4,7-trioxo-3,4,6,7-tetrahydro-2H-pyrido[4,3-d]pyrimidin-1-yl]-phenyl}-acetamide

HRID 75678Notes

Reaction equation

HRID 75678 reaction equation
[F:1][C:2]1[CH:7]=[C:6]([I:8])[CH:5]=[CH:4][C:3]=1[NH:9][C:10]1[N:11]([CH3:43])[C:12](=[O:42])[C:13]([CH3:41])=[C:14]2[C:19]=1[C:18](=[O:20])[N:17](CC1C=CC(OC)=CC=1)[C:16](=[O:30])[N:15]2[C:31]1[CH:32]=[C:33]([NH:37][C:38](=[O:40])[CH3:39])[CH:34]=[CH:35][CH:36]=1.[Cl-].[Al+3].[Cl-].[Cl-].CO>C1(OC)C=CC=CC=1>[F:1][C:2]1[CH:7]=[C:6]([I:8])[CH:5]=[CH:4][C:3]=1[NH:9][C:10]1[N:11]([CH3:43])[C:12](=[O:42])[C:13]([CH3:41])=[C:14]2[C:19]=1[C:18](=[O:20])[NH:17][C:16](=[O:30])[N:15]2[C:31]1[CH:32]=[C:33]([NH:37][C:38](=[O:40])[CH3:39])[CH:34]=[CH:35][CH:36]=1

Participants

5

Reactant 3

HCID 887MethanolHCID 6451240Aluminum(III) ChlorideHCID 59717341N-{3-[5-(2-fluoro-4-iodophenylamino)-3-(4-methoxybenzyl)-6,8-dimethyl-2,4,7-trioxo-3,4,6,7-tetrahydro-2H-pyrido[4,3-d]pyrimidin-1-yl]-phenyl}-acetamide

Product 1

HCID 59717419N-{3-[5-(2-fluoro-4-iodophenylamino)-6,8-dimethyl-2,4,7-trioxo-3,4,6,7-tetrahydro-2H-pyrido[4,3-d]pyrimidin-1-yl]-phenyl}-acetamideYield 78.1%

Reagents, catalysts & solvents 1

HCID 7519AnisoleSolvent

Procedure

To a suspension of N-{3-[5-(2-fluoro-4-iodophenylamino)-3-(4-methoxybenzyl)-6,8-dimethyl-2,4,7-trioxo-3,4,6,7-tetrahydro-2H-pyrido[4,3-d]pyrimidin-1-yl]-phenyl}-acetamide 88 (960 mg) in anisole (10.0 ml) was added aluminum chloride (1.94 g) with stirring in a water bath. The mixture was stirred at room temperature for 37 hrs, methanol (12.0 ml) was added dropwise, and the mixture was concentrated under reduced pressure. The obtained residue was dissolved in methanol (12.0 ml), and 2N hydrochloric acid (20.0 ml) was added dropwise with stirring in a water bath. The mixture was stirred at room temperature for 1 hr, hexane (10.0 ml) was added, and the mixture was stirred for 1 hr. The precipitated crystals were collected by filtration, washed with hexane, water and methanol, and dried to give N-{3-[5-(2-fluoro-4-iodophenylamino)-6,8-dimethyl-2,4,7-trioxo-3,4,6,7-tetrahydro-2H-pyrido[4,3-d]pyrimidin-1-yl]-phenyl}-acetamide 89 (620 mg, yield 78.1%) as colorless crystals.

Workup

  1. stirringThe mixture was stirred at room temperature for 37 hrs
  2. concentrationthe mixture was concentrated under reduced pressure
  3. dissolutionThe obtained residue was dissolved in methanol (12.0 ml)
  4. addition2N hydrochloric acid (20.0 ml) was added dropwise
  5. stirringwith stirring in a water bath
  6. stirringThe mixture was stirred at room temperature for 1 hr
  7. additionhexane (10.0 ml) was added
  8. stirringthe mixture was stirred for 1 hr
  9. filtrationThe precipitated crystals were collected by filtration
  10. washwashed with hexane, water and methanol
  11. customdried

Sources & evidence

ORD record
ord-3b6a4ce65e7d4f6a98f789fea6faa1a9
Source dataset
uspto-grants-2014_09
Patent number
US08835443B2

Reaction notes

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