Acetic Acid → Trametinib

HRID 75654Notes

Reaction equation

HRID 75654 reaction equation
C[O-].[Na+].O1CCCC1.[CH:9]1([N:12]2[C:17](=[O:18])[C:16]3[C:19]([NH:26][C:27]4[CH:28]=[C:29]([NH:33][C:34](=[O:36])[CH3:35])[CH:30]=[CH:31][CH:32]=4)=[C:20]([CH3:25])[C:21](=[O:24])[N:22]([CH3:23])[C:15]=3[N:14]([C:37]3[CH:42]=[CH:41][C:40]([I:43])=[CH:39][C:38]=3[F:44])[C:13]2=[O:45])[CH2:11][CH2:10]1.C(O)(=O)C>CO.O>[CH:9]1([N:12]2[C:17](=[O:18])[C:16]3=[C:15]([NH:14][C:37]4[CH:42]=[CH:41][C:40]([I:43])=[CH:39][C:38]=4[F:44])[N:22]([CH3:23])[C:21](=[O:24])[C:20]([CH3:25])=[C:19]3[N:26]([C:27]3[CH:28]=[C:29]([NH:33][C:34](=[O:36])[CH3:35])[CH:30]=[CH:31][CH:32]=3)[C:13]2=[O:45])[CH2:11][CH2:10]1

Participants

7

Reactant 4

HCID 176Acetic AcidHCID 8028TetrahydrofuranHCID 10942334Sodium MethoxideHCID 59717354N-[3-[[3-Cyclopropyl-1-(2-fluoro-4-iodophenyl)-1,2,3,4,7,8-hexahydro-6,8-dimethyl-2,4,7-trioxopyrido[2,3-d]pyrimidin-5-yl]amino]phenyl]acetamide

Product 1

HCID 11707110TrametinibYield 95%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 962WaterSolvent

Procedure

Under a nitrogen atmosphere, to a solution (1.57 g) of 28% sodium methoxide in methanol was added tetrahydrofuran (40 ml), N-{3-[3-cyclopropyl-1-(2-fluoro-4-iodophenyl)-6,8-dimethyl-2,4,7-trioxo-1,2,3,4,7,8-hexahydro-pyrido[2,3-d]pyrimidin-5-ylamino]phenyl}acetamide 58 (5.00 g) obtained in Step 7 was added, and the mixture was stirred at room temperature for 4 hrs. Acetic acid (0.56 ml) was added, and the mixture was stirred at room temperature for 30 min. Water (40 ml) was added and the mixture was further stirred for 1 hr. The crystals were collected by filtration and dried to give N-{3-[3-cyclopropyl-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 59 (4.75 g, yield 95%) as colorless crystals.

Workup

  1. additionwas added
  2. stirringthe mixture was stirred at room temperature for 30 min
  3. stirringthe mixture was further stirred for 1 hr
  4. filtrationThe crystals were collected by filtration
  5. customdried

Sources & evidence

ORD record
ord-249e8ebaceb74257abb85318283dab71
Source dataset
uspto-grants-2014_09
Patent number
US08835443B2

Reaction notes

Loading…