Hydrochloric Acid → Selumetinib

HRID 504189Notes

Reaction equation

HRID 504189 reaction equation
Cl.C([O:4][CH2:5][CH2:6][O:7][NH:8][C:9]([C:11]1[C:20]([NH:21][C:22]2[CH:27]=[CH:26][C:25]([Br:28])=[CH:24][C:23]=2[Cl:29])=[C:19]([F:30])[C:14]2[N:15]=[CH:16][N:17]([CH3:18])[C:13]=2[CH:12]=1)=[O:10])=C>C(O)C>[OH:4][CH2:5][CH2:6][O:7][NH:8][C:9]([C:11]1[C:20]([NH:21][C:22]2[CH:27]=[CH:26][C:25]([Br:28])=[CH:24][C:23]=2[Cl:29])=[C:19]([F:30])[C:14]2[N:15]=[CH:16][N:17]([CH3:18])[C:13]=2[CH:12]=1)=[O:10]

Participants

4

Reactant 2

HCID 313Hydrochloric AcidHCID 707006695-((4-Bromo-2-chlorophenyl)amino)-4-fluoro-1-methyl-N-(2-(vinyloxy)ethoxy)-1H-benzo[d]imidazole-6-carboxamide

Product 1

HCID 10127622SelumetinibYield 102.4%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

Hydrochloric acid (14 mL, 1.0 M aqueous solution, 14 mmol) is added to a suspension of 6-(4-bromo-2-chloro-phenylamino)-7-fluoro-3-methyl-3H-benzoimidazole-5-carboxylic acid (2-vinyloxy-ethoxy)-amide 29a (2.18 g, 4.50 mmol) in ethanol (50 mL) and the reaction mixture allowed to stir for 24 hours. The reaction mixture is concentrated to dryness by rotary evaporation and the solids partitioned between 3:1 ethyl acetate/tetrahydrofuran and saturated potassium carbonate. The aqueous phase is extracted with 3:1 ethyl acetate/tetrahydrofuran (3×), the combined organics dried (Na2SO4), and concentrated to provide 2.11 g (100%) 6-(4-bromo-2-chloro-phenylamino)-7-fluoro-3-methyl-3H-benzoimidazole-5-carboxylic acid (2-hydroxy-ethoxy)-amide as an off-white solid. MS ESI (+) m/z 457, 459 (M+, Br pattern) detected. 1H NMR (100 MHz, MeOH-d4) δ 8.26 (s, 1H), 7.78 (s, 1H), 7.57 (d, 1H), 7.24 (dd, 1H), 6.40 (dd, 1H), 3.86 (s, 3H), 3.79 (m, 2H), 3.49 (m, 2H). 19F NMR (376 MHz, MeOH-d4) −133.68 (s).

Workup

  1. concentrationThe reaction mixture is concentrated to dryness by rotary evaporation
  2. customthe solids partitioned between 3:1 ethyl acetate/tetrahydrofuran and saturated potassium carbonate
  3. extractionThe aqueous phase is extracted with 3:1 ethyl acetate/tetrahydrofuran (3×)
  4. dry with materialthe combined organics dried (Na2SO4)
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-50bafcd88ce546678e2eeaf44a0b938b
Source dataset
uspto-grants-2010_08
Patent number
US07777050B2

Reaction notes

Loading…