Potassium Phosphate, Tribasic → HCID 71736739, compound

HRID 2172318Notes

Reaction equation

HRID 2172318 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]=[C:22]([C:24]([F:27])([F:26])[F:25])[CH:21]=[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.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]=[CH:21][C:22]([C:24]([F:26])([F:25])[F:27])=[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

6

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 89813497HCID 89813497, compound

Product 1

HCID 71736739HCID 71736739, compoundYield 28.6%

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Procedure

A solution of Cl2Pd(AmPhos) (Sigma-Aldrich, St. Louis, Mo., 0.020 g, 0.028 mmol), 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,2,3,6-tetrahydropyridine (0.078 g, 0.350 mmol), 5-(2-bromo-4-(trifluoromethyl)phenyl)-N-(5-fluorothiazol-2-yl)-3,4-dihydroisoquinoline-2(1H)-sulfonamide (0.150 g, 0.280 mmol), and potassium phosphate (0.237 g, 1.119 mmol) in 2 mL dioxane 1 mL water, was heated to 110° C. 2 hours. After cooling to rt, the reaction mixture 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)-4-(trifluoromethyl)phenyl)-3,4-dihydroisoquinoline-2(1H)-sulfonamide (0.044 g, 0.080 mmol). [M+H]+=553.0 1H NMR (400 MHz, Acetone-d6) δ ppm: 7.72 (d, J=7.8 Hz, 1H), 7.57 (s, 1H), 7.36 (d, J=7.9 Hz, 1H), 7.03-7.14 (m, 2H), 6.93 (d, J=7.5 Hz, 1H), 6.58-6.64 (m, 1H), 5.92 (br. s., 1H), 4.53 (d, J=17.3 Hz, 1H), 4.19 (d, J=17.6 Hz, 1H), 3.71-3.84 (m, 2H), 3.13-3.46 (m, 4H), 2.86-2.99 (m, 1H), 2.75-2.86 (m, 1H), 2.53-2.60 (s, 3H), 1.94-2.19 (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-7d0a8b9c812b43b9a2c04b346198eebf
Source dataset
uspto-grants-2015_06
Patent number
US09051311B2

Reaction notes

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