Methanol → Trametinib

HRID 710587Notes

Reaction equation

HRID 710587 reaction equation
O1CCCC1.[CH:6]1([N:9]2[C:14](=[O:15])[C:13]3[C:16]([NH:23][C:24]4[CH:25]=[C:26]([NH:30][C:31](=[O:33])[CH3:32])[CH:27]=[CH:28][CH:29]=4)=[C:17]([CH3:22])[C:18](=[O:21])[N:19]([CH3:20])[C:12]=3[N:11]([C:34]3[CH:39]=[CH:38][C:37]([I:40])=[CH:36][C:35]=3[F:41])[C:10]2=[O:42])[CH2:8][CH2:7]1.CO.C[O-].[Na+]>O.C(O)(=O)C>[CH3:22][C:17]1[C:18](=[O:21])[N:19]([CH3:20])[C:12]([NH:11][C:34]2[CH:39]=[CH:38][C:37]([I:40])=[CH:36][C:35]=2[F:41])=[C:13]2[C:14]([N:9]([CH:6]3[CH2:8][CH2:7]3)[C:10]([N:23]([C:24]3[CH:29]=[CH:28][CH:27]=[C:26]([NH:30][C:31]([CH3:32])=[O:33])[CH:25]=3)[C:16]=12)=[O:42])=[O:15]

Participants

7

Reactant 4

HCID 887MethanolHCID 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 176Acetic AcidSolventHCID 962WaterSolvent

Procedure

Under a nitrogen atmosphere, tetrahydrofuran (40 mL) was added to N-{3-[3-cyclopropyl-1-(2-fluoro-4-iodo-phenyl)-6,8-dimethyl-2,4,7-trioxo-1,2,3,4,7,8-hexahydro-pyrido[2,3-d]pyrimidin-5-ylamino]-phenyl}-acetamide (5 g) and a methanol solution (1.57 g) containing 28% sodium methoxide was added and the mixture was stirred at room temperature for 4 hours. Acetic acid (0.56 mL) was added to the mixture and the mixture was stirred at room temperature for 30 min. And then water (40 mL) was added and the mixture was further stirred for 1 hour. The crystals were collected by filtration and dried under reduced pressure at 40° C. to give trametinib (4.75 g). Its HPLC content of A impurity is 0.42 wt %.

Workup

  1. additionwas added
  2. stirringthe mixture was stirred at room temperature for 30 min
  3. stirringthe mixture was further stirred for 1 hour
  4. filtrationThe crystals were collected by filtration
  5. customdried under reduced pressure at 40° C.

Sources & evidence

ORD record
ord-cd5be3be791a499f9a6894ecc5afd2f6
Source dataset
uspto-grants-2015_11
Patent number
US09181243B2

Reaction notes

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