Potassium Phosphate, Tribasic → HCID 71737520, compound

HRID 2172305Notes

Reaction equation

HRID 2172305 reaction equation
CC1(C)C(C)(C)OB([C:9]2[CH2:14][CH2:13][N:12]([C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[CH2:11][CH:10]=2)O1.Br[C:24]1[CH:29]=[C:28]([C:30]([F:33])([F:32])[F:31])[CH:27]=[CH:26][C:25]=1[C:34]1[CH:43]=[CH:42][CH:41]=[C:40]2[C:35]=1[CH2:36][CH2:37][N:38]([S:44]([NH:47][C:48]1[S:52][N:51]=[CH:50][N:49]=1)(=[O:46])=[O:45])[CH2:39]2.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>O1CCOCC1.O.CCOC(C)=O>[S:52]1[C:48]([NH:47][S:44]([N:38]2[CH2:37][CH2:36][C:35]3[C:40](=[CH:41][CH:42]=[CH:43][C:34]=3[C:25]3[CH:26]=[CH:27][C:28]([C:30]([F:33])([F:32])[F:31])=[CH:29][C:24]=3[C:9]3[CH2:14][CH2:13][N:12]([C:15]([O:17][C:18]([CH3:19])([CH3:20])[CH3:21])=[O:16])[CH2:11][CH:10]=3)[CH2:39]2)(=[O:46])=[O:45])=[N:49][CH:50]=[N:51]1

Participants

7

Reactant 3

HCID 62657Potassium Phosphate, TribasicHCID 4642098Tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,2,3,6-tetrahydropyridine-1-carboxylateHCID 71735778HCID 71735778, compound

Product 1

HCID 71737520HCID 71737520, compoundYield 53%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Procedure

A solution of Cl2Pd(AmPhos) (Sigma-Aldrich, St. Louis, Mo., 0.136 g, 0.193 mmol), tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-5,6-dihydropyridine-1(2H)-carboxylate (Frontier Scientific, Logan, Utah, 1.191 g, 3.85 mmol), 5-(2-bromo-4-(trifluoromethyl)phenyl)-N-(1,2,4-thiadiazol-5-yl)-3,4-dihydroisoquinoline-2(1H)-sulfonamide (Example 4, 1.000 g, 1.925 mmol), and potassium phosphate (1.635 g, 7.70 mmol) in 20 mL dioxane, 10 mL water was heated to 120° C. for 2 hours. The reaction mixture was diluted with EtOAc and washed with 1 N citric acid solution. The organics were dried over MgSO4 and concentrated. Purification of the resulting residue by silica gel column chromatography (0 to 100% EtOAc/heptane) gave tert-butyl 4-(2-(2-(N-(1,2,4-thiadiazol-5-yl)sulfamoyl)-1,2,3,4-tetrahydroisoquinolin-5-yl)-5-(trifluoromethyl)phenyl)-5,6-dihydropyridine-1(2H)-carboxylate (0.635 g, 1.021 mmol). [M+H]+=522.0 1H NMR (400 MHz, Acetone-d6) δ ppm: 8.28 (s, 1H), 7.63-7.70 (m, 2H), 7.43 (d, J=7.8 Hz, 1H), 7.15-7.30 (m, 2H), 7.07 (d, J=7.4 Hz, 1H), 5.72 (s, 1H), 4.31-4.44 (m, 2H), 3.87 (br. s., 2H), 3.41-3.48 (m, 1H), 3.16-3.36 (m, 1H), 2.78 (br. s., 4H), 2.69 (m, 1H), 2.48-2.55 (m, 1H), 1.37-1.47 (m, 9H)

Workup

  1. washwashed with 1 N citric acid solution
  2. dry with materialThe organics were dried over MgSO4
  3. concentrationconcentrated
  4. customPurification of the resulting residue by silica gel column chromatography (0 to 100% EtOAc/heptane)

Sources & evidence

ORD record
ord-348d114fb69b4354a9e0a5a4465dfa3f
Source dataset
uspto-grants-2015_06
Patent number
US09051311B2

Reaction notes

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