Hydrochloric Acid → Selumetinib

HRID 31983

반응식

HRID 31983 반응식
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]

참가 물질

4

반응물 2

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

생성물 1

HCID 10127622Selumetinib수율 102.4%

시약·촉매·용매 1

HCID 702Ethanol용매

실험 절차

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-2chloro-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 (400 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).

후처리

  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

출처 및 근거

ORD 기록
ord-016d19133d9e47df94b707f2158d055f
출처 데이터셋
uspto-grants-2008_09
특허 번호
US07425637B2

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