Water → Selumetinib sulfate

HRID 1749193Notes

Reaction equation

HRID 1749193 reaction equation
[S:1](=[O:5])(=[O:4])([OH:3])[OH:2].[OH:6][CH2:7][CH2:8][O:9][NH:10][C:11]([C:13]1[C:22]([NH:23][C:24]2[CH:29]=[CH:28][C:27]([Br:30])=[CH:26][C:25]=2[Cl:31])=[C:21]([F:32])[C:16]2[N:17]=[CH:18][N:19]([CH3:20])[C:15]=2[CH:14]=1)=[O:12].O>O1CCCC1>[S:1]([OH:5])([OH:4])(=[O:3])=[O:2].[OH:6][CH2:7][CH2:8][O:9][NH:10][C:11]([C:13]1[C:22]([NH:23][C:24]2[CH:29]=[CH:28][C:27]([Br:30])=[CH:26][C:25]=2[Cl:31])=[C:21]([F:32])[C:16]2[N:17]=[CH:18][N:19]([CH3:20])[C:15]=2[CH:14]=1)=[O:12]

Participants

5

Reactant 3

HCID 962WaterHCID 1118Sulfuric AcidHCID 10127622Selumetinib

Product 1

HCID 16214875Selumetinib sulfateYield 794.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
65 °C

Procedure

Sulfuric acid (1.52 ml, 27.86 mmol) was added to a stirred suspension of 6-(4-bromo-2-chlorophenylamino)-7-fluoro-3-methyl-3H-benzoimidazole-5-carboxylic acid (2-hydroxyethoxy)-amide (10 g, 0.0214 mol) (obtainable as described in Example 10 of WO 03/077914, which is incorporated herein by reference and as described below) in tetrahydrofuran (THF) (62 ml) and water (8 ml) whilst maintaining a temperature of 10° C. or lower. The stirred mixture was heated to 65° C. and held for 30 minutes before filtering to remove any extraneous matter. THF (150 ml) was then added to the mixture maintaining the temperature above 60° C. The mixture was then cooled to 0-5° C. over approximately 2 hour. The resulting slurry was filtered, washed with THF (30 ml) and dried under reduced pressure at 50° C. until a constant weight was achieved, to give 6-(4-bromo-2-chlorophenylamino)-7-fluoro-3-methyl-3H-benzoimidazole-5-carboxylic acid (2-hydroxyethoxy)-amide hydrogen sulfate (9.81 g, 0.17 mol, 82% yield) as an off white crystalline solid. The material was the same as that produced in Example 1 above.

Workup

  1. filtrationbefore filtering
  2. customto remove any extraneous matter
  3. additionTHF (150 ml) was then added to the mixture
  4. temperaturemaintaining the temperature above 60° C
  5. temperatureThe mixture was then cooled to 0-5° C. over approximately 2 hour
  6. filtrationThe resulting slurry was filtered
  7. washwashed with THF (30 ml)
  8. customdried under reduced pressure at 50° C. until a constant weight

Sources & evidence

ORD record
ord-ea261e2ca0b34b4a80b51c18ad8653ac
Source dataset
uspto-grants-2015_10
Patent number
US09156795B2

Reaction notes

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