Hydrochloric Acid → (S)-N-(7-(2-(1-amino-2-(3,5-difluorophenyl)ethyl)-6-((2-hydroxyethyl)(methyl)amino)pyridin-3-yl)-4-chloro-1-methyl-1H-indazol-3-yl)methanesulfonamide

HRID 2170399Notes

Reaction equation

HRID 2170399 reaction equation
[Cl:1][C:2]1[CH:10]=[CH:9][C:8]([C:11]2[C:12]([C@@H:22]([NH:32]C(=O)C(F)(F)F)[CH2:23][C:24]3[CH:29]=[C:28]([F:30])[CH:27]=[C:26]([F:31])[CH:25]=3)=[N:13][C:14]([N:17]([CH2:19][CH2:20][OH:21])[CH3:18])=[CH:15][CH:16]=2)=[C:7]2[C:3]=1[C:4]([NH:40][S:41]([CH3:44])(=[O:43])=[O:42])=[N:5][N:6]2[CH3:39].[OH-].[Li+].Cl>CCO>[NH2:32][C@H:22]([C:12]1[C:11]([C:8]2[CH:9]=[CH:10][C:2]([Cl:1])=[C:3]3[C:7]=2[N:6]([CH3:39])[N:5]=[C:4]3[NH:40][S:41]([CH3:44])(=[O:42])=[O:43])=[CH:16][CH:15]=[C:14]([N:17]([CH2:19][CH2:20][OH:21])[CH3:18])[N:13]=1)[CH2:23][C:24]1[CH:25]=[C:26]([F:31])[CH:27]=[C:28]([F:30])[CH:29]=1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 3939Lithium HydroxideHCID 90281439(S)-N-(1-(3-(4-chloro-1-methyl-3-(methylsulfonamido)-1H-indazol-7-yl)-6-((2-hydroxyethyl)(methyl)amino)pyridin-2-yl)-2-(3,5-difluorophenyl)ethyl)-2,2,2-trifluoroacetamide

Product 1

HCID 90281351(S)-N-(7-(2-(1-amino-2-(3,5-difluorophenyl)ethyl)-6-((2-hydroxyethyl)(methyl)amino)pyridin-3-yl)-4-chloro-1-methyl-1H-indazol-3-yl)methanesulfonamide

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
130 °C

Procedure

To a solution of crude (S)—N-(1-(3-(4-chloro-1-methyl-3-(methylsulfonamido)-1H-indazol-7-yl)-6-((2-hydroxyethyl)(methyl)amino)pyridin-2-yl)-2-(3,5-difluorophenyl)ethyl)-2,2,2-trifluoroacetamide (57E) in EtOH (1 mL) was added aqueous 2M lithium hydroxide (0.4 mL). The reaction was heated at 130° C. in a microwave reactor for 5 minutes. Upon cooling, aqueous 2N HCl was added until the solution became slightly acidic (pH 4-5). The reaction mixture was then concentrated and taken up in equal volumes of EtOAc and saturated aqueous NaHCO3. The organic layer was collected and the aqueous layer was extracted with a second volume of EtOAc. The combined organic layers were dried over Na2SO4, filtered, concentrated in vacuo, and used without further purification. MS (m/z) 565.09 [M+H]+.

Workup

  1. temperatureUpon cooling
  2. concentrationThe reaction mixture was then concentrated
  3. customThe organic layer was collected
  4. extractionthe aqueous layer was extracted with a second volume of EtOAc
  5. dry with materialThe combined organic layers were dried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customused without further purification

Sources & evidence

ORD record
ord-9e39a3ed292d4e68b99a3320936d7046
Source dataset
uspto-grants-2015_06
Patent number
US09050344B2

Reaction notes

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