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

HRID 2170402Notes

Reaction equation

HRID 2170402 reaction equation
[Cl:1][C:2]1[N:7]=[C:6]([C@@H:8]([NH:18]C(=O)C(F)(F)F)[CH2:9][C:10]2[CH:15]=[C:14]([F:16])[CH:13]=[C:12]([F:17])[CH:11]=2)[C:5]([C:25]2[CH:26]=[CH:27][C:28]([Cl:40])=[C:29]3[C:33]=2[N:32]([CH3:34])[N:31]=[C:30]3[NH:35][S:36]([CH3:39])(=[O:38])=[O:37])=[CH:4][CH:3]=1.[Li+].[OH-].Cl>CCO>[NH2:18][C@H:8]([C:6]1[C:5]([C:25]2[CH:26]=[CH:27][C:28]([Cl:40])=[C:29]3[C:33]=2[N:32]([CH3:34])[N:31]=[C:30]3[NH:35][S:36]([CH3:39])(=[O:37])=[O:38])=[CH:4][CH:3]=[C:2]([Cl:1])[N:7]=1)[CH2:9][C:10]1[CH:15]=[C:14]([F:16])[CH:13]=[C:12]([F:17])[CH:11]=1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 3939Lithium HydroxideHCID 90281429(S)-N-(1-(6-chloro-3-(4-chloro-1-methyl-3-(methylsulfonamido)-1H-indazol-7-yl)pyridin-2-yl)-2-(3,5-difluorophenyl)ethyl)-2,2,2-trifluoroacetamide

Product 1

HCID 90281213(S)-N-(7-(2-(1-amino-2-(3,5-difluorophenyl)ethyl)-6-chloropyridin-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 (S)—N-(1-(6-chloro-3-(4-chloro-1-methyl-3-(methylsulfonamido)-1H-indazol-7-yl)pyridin-2-yl)-2-(3,5-difluorophenyl)ethyl)-2,2,2-trifluoroacetamide (57D, 870 mg, 1.40 mmol) in EtOH (16 mL) was added 2M aqueous LiOH (7.0 mL, 13.98 mmol). The reaction was heated in a microwave reactor at 130° C. for 10 minutes. Upon cooling, the reaction mixture was acidified with 2N aqueous HCl until at pH 5. The reaction mixture was then concentrated in vacuo and taken in EtOAc. To the solution was added saturated aqueous NaHCO3 until the aqueous layer was at pH 10. The organic layer was collected, and the aqueous layer was extracted an additional time with EtOAc. The combined organic layers were dried over Na2SO4, filtered, concentrated in vacuo, and used without further purification. MS (m/z) 526.06 [M+H]+.

Workup

  1. temperatureUpon cooling
  2. concentrationThe reaction mixture was then concentrated in vacuo
  3. additionTo the solution was added saturated aqueous NaHCO3 until the aqueous layer
  4. customThe organic layer was collected
  5. extractionthe aqueous layer was extracted an additional time with EtOAc
  6. dry with materialThe combined organic layers were dried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customused without further purification

Sources & evidence

ORD record
ord-8ffe87717439431f8e9afcbd0894a979
Source dataset
uspto-grants-2015_06
Patent number
US09050344B2

Reaction notes

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