Sodium Chloride → Baxdrostat Impurity 30

HRID 530323Notes

Reaction equation

HRID 530323 reaction equation
Br[C:2]1[C:11]2[CH2:10][CH2:9][CH2:8][CH:7]([NH2:12])[C:6]=2[CH:5]=[N:4][CH:3]=1.[CH3:13][N:14]1[C:23]2[C:18](=[CH:19][C:20](B3OC(C)(C)C(C)(C)O3)=[CH:21][CH:22]=2)[CH2:17][CH2:16][C:15]1=[O:33].C([O-])([O-])=O.[Na+].[Na+].[Na+].[Cl-]>C(O)C.O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[NH2:12][CH:7]1[C:6]2[CH:5]=[N:4][CH:3]=[C:2]([C:20]3[CH:19]=[C:18]4[C:23](=[CH:22][CH:21]=3)[N:14]([CH3:13])[C:15](=[O:33])[CH2:16][CH2:17]4)[C:11]=2[CH2:10][CH2:9][CH2:8]1

Participants

8

Reactant 4

HCID 5234Sodium ChlorideHCID 10340Sodium CarbonateHCID 717433794-Bromo-5,6,7,8-tetrahydroisoquinolin-8-amineHCID 722082331-methyl-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3,4-dihydroquinolin-2(1H)-one

Product 1

HCID 71538469Baxdrostat Impurity 30Yield 137.9%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 702EthanolSolventHCID 962WaterSolvent

Conditions

Temperature
85 °C

Procedure

In a 100 mL round-bottomed flask, (rac)-4-bromo-5,6,7,8-tetrahydroisoquinolin-8-amine (745 mg, 3.28 mmol) and 1-methyl-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3,4-dihydroquinolin-2(1H)-one (intermediate A-1) (1.13 g, 3.94 mmol) were dissolved in ethanol (60 mL) to give a light brown solution. Na2CO3 (382 mg, 3.61 mmol), dissolved in water (10 mL) was added followed by tetrakis(triphenylphosphine)palladium (0) (114 mg, 98.4 μmol) after evacuation and replacing 5 times with Argon. The solution was then heated at 85° C. overnight. The reaction was treated with an aq. 10% NaCl solution and extracted with AcOEt (3×). The organic phases were washed again with an aq. 10% NaCl solution, dried over Na2SO4, filtered and evaporated under reduced pressure to give 1.39 g brown foam which was purified by flash chromatography (50 g SiO2, Telos-cartridge, CH2Cl2/MeOH (3, 5, 7.5, 10 and 15%)) and precipitated from CH2Cl2 with n-pentane to give the title compound (690 mg, 68%) as a light brown foam. MS: 308.2 (M+H+).

Workup

  1. customto give a light brown solution
  2. additionwas added
  3. extractionextracted with AcOEt (3×)
  4. washThe organic phases were washed again with an aq. 10% NaCl solution
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. customevaporated under reduced pressure

Sources & evidence

ORD record
ord-2212ed9729ce4bb4901d631b43a9f4ea
Source dataset
uspto-grants-2016_05
Patent number
US09353081B2

Reaction notes

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