1,4-Dioxane → HCID 71735779, compound

HRID 2172307Notes

Reaction equation

HRID 2172307 reaction equation
[F:1][C:2]([F:13])([F:12])[C:3]1[CH:8]=[CH:7][C:6](B(O)O)=[CH:5][CH:4]=1.Br[C:15]1[CH:24]=[CH:23][CH:22]=[C:21]2[C:16]=1[CH2:17][CH2:18][N:19]([S:25]([NH:28][C:29]1[S:33][N:32]=[CH:31][N:30]=1)(=[O:27])=[O:26])[CH2:20]2.P([O-])([O-])([O-])=O.[K+].[K+].[K+].O1CCOCC1>O>[S:33]1[C:29]([NH:28][S:25]([N:19]2[CH2:18][CH2:17][C:16]3[C:21](=[CH:22][CH:23]=[CH:24][C:15]=3[C:6]3[CH:7]=[CH:8][C:3]([C:2]([F:13])([F:12])[F:1])=[CH:4][CH:5]=3)[CH2:20]2)(=[O:26])=[O:27])=[N:30][CH:31]=[N:32]1

Participants

6

Reactant 4

HCID 312751,4-DioxaneHCID 62657Potassium Phosphate, TribasicHCID 27343894-(Trifluoromethyl)phenylboronic acidHCID 89813529HCID 89813529, compound

Product 1

HCID 71735779HCID 71735779, compound

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
120 °C

Procedure

A vial charged with Cl2Pd(AmPhos) (Sigma-Aldrich, St. Louis, Mo., 9.43 μg, 0.013 μmol), (4-(trifluoromethyl)phenyl)boronic acid (0.200 μmol), 5-bromo-N-(1,2,4-thiadiazol-5-yl)-3,4-dihydroisoquinoline-2(1H)-sulfonamide (0.050 mg, 0.133 μmol), and potassium phosphate (0.085 mg, 0.400 μmol) was treated with 2 mL dioxane and 1 mL water. The reaction mixture was heated to 120° C. for 2 hours at which time the mixture was cooled to room temperature then concentrated and purified by reverse phase column chromatography [RediSep Gold C-18 50 g, 5 to 75% (0.1% NH4OH in MeOH)/(0.1% NH4OH in water)] to provide N-(1,2,4-thiadiazol-5-yl)-5-(4-(trifluoromethyl)phenyl)-3,4-dihydroisoquinoline-2(1H)-sulfonamide. [M+H]+=441.0. 1H NMR (400 MHz, MeOH-d4) δ ppm: 8.03 (s, 1H), 7.72 (d, J=8.1 Hz, 2H), 7.49 (d, J=7.9 Hz, 2H), 7.22-7.28 (m, 1H), 7.12 (dd, J=15.5, 7.1 Hz, 2H), 4.40 (s, 2H), 3.33-3.38 (m, 2H), 2.77 (m, 2H)

Workup

  1. temperaturewas cooled to room temperature
  2. concentrationthen concentrated
  3. custompurified by reverse phase column chromatography [RediSep Gold C-18 50 g, 5 to 75% (0.1% NH4OH in MeOH)/(0.1% NH4OH in water)]

Sources & evidence

ORD record
ord-2935221556a6437aa582f3aa36eecef7
Source dataset
uspto-grants-2015_06
Patent number
US09051311B2

Reaction notes

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