Potassium Phosphate, Tribasic → HCID 71736740, compound

HRID 2172320Notes

Reaction equation

HRID 2172320 reaction equation
[CH3:1][N:2]1[CH2:7][CH:6]=[C:5](B2OC(C)(C)C(C)(C)O2)[CH2:4][CH2:3]1.Br[C:18]1[CH:23]=[CH:22][C:21]([C:24]([F:27])([F:26])[F:25])=[CH:20][C:19]=1[C:28]1[CH:37]=[CH:36][CH:35]=[C:34]2[C:29]=1[CH2:30][CH2:31][N:32]([S:38]([NH:41][C:42]1[S:43][C:44]([F:47])=[CH:45][N:46]=1)(=[O:40])=[O:39])[CH2:33]2.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>O1CCOCC1.O.CCOC(C)=O>[F:47][C:44]1[S:43][C:42]([NH:41][S:38]([N:32]2[CH2:31][CH2:30][C:29]3[C:34](=[CH:35][CH:36]=[CH:37][C:28]=3[C:19]3[CH:20]=[C:21]([C:24]([F:26])([F:25])[F:27])[CH:22]=[CH:23][C:18]=3[C:5]3[CH2:4][CH2:3][N:2]([CH3:1])[CH2:7][CH:6]=3)[CH2:33]2)(=[O:39])=[O:40])=[N:46][CH:45]=1

Participants

7

Reactant 3

HCID 62657Potassium Phosphate, TribasicHCID 207733711-Methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,2,3,6-tetrahydropyridineHCID 89813933HCID 89813933, compound

Product 1

HCID 71736740HCID 71736740, compoundYield 10.3%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Procedure

A solution of Cl2Pd(AmPhos) (Sigma-Aldrich, St. Louis, Mo., 0.014 g, 0.019 mmol), 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,2,3,6-tetrahydropyridine (0.054 g, 0.242 mmol), 5-(2-bromo-5-(trifluoromethyl)phenyl)-N-(5-fluorothiazol-2-yl)-3,4-dihydroisoquinoline-2(1H)-sulfonamide (0.104 g, 0.194 mmol), and potassium phosphate (0.165 g, 0.776 mmol) in 2 mL dioxane and 1 mL water, was heated to 110° C. 2 hours. The reaction mixture was allowed to cool to room temperature, was diluted with EtOAc and washed with 1N citric acid. The organic layer was then concentrated. Purification of the resulting residue by reverse phase column chromatography [RediSep Gold C18 50 g, 10 to 100% (0.1% NH4OH in MeOH)/(0.1% NH4OH in water)] gave N-(5-fluorothiazol-2-yl)-5-(2-(1-methyl-1,2,3,6-tetrahydropyridin-4-yl)-5-(trifluoromethyl)phenyl)-3,4-dihydroisoquinoline-2(1H)-sulfonamide (0.011 g, 0.020 mmol). [M+H]+=553.0 1H NMR (400 mHz, Acetone-d6) δ ppm: 7.70-7.77 (m, 1H), 7.50 (d, J=8.1 Hz, 1H), 7.42 (s, 1H), 7.05-7.14 (m, 2H), 6.93 (d, J=6.7 Hz, 1H), 6.62 (d, J=0.9 Hz, 1H), 5.87-5.93 (m, 1H), 4.48-4.56 (d, J=17.4 Hz, 1H), 4.19 (d, J=17.4 Hz, 1H), 3.70-3.84 (m, 2H), 3.32-3.43 (m, 1H), 3.12-3.32 (m, 3H), 2.87-2.98 (m, 1H), 2.76-2.82 (m, 1H), 2.57 (s, 3H), 1.98-2.04 (m, 2H)

Workup

  1. custom2 hours
  2. washwashed with 1N citric acid
  3. concentrationThe organic layer was then concentrated
  4. customPurification of the resulting residue by reverse phase column chromatography [RediSep Gold C18 50 g, 10 to 100% (0.1% NH4OH in MeOH)/(0.1% NH4OH in water)]

Sources & evidence

ORD record
ord-2247104bd5364b2487518f87eabf29af
Source dataset
uspto-grants-2015_06
Patent number
US09051311B2

Reaction notes

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