Hydrochloric Acid → HCID 71737517, compound

HRID 2172336Notes

Reaction equation

HRID 2172336 reaction equation
Br[C:2]1[CH:11]=[CH:10][CH:9]=[C:8]2[C:3]=1[CH2:4][CH2:5][N:6]([S:12]([NH:15][C:16]1[S:17][CH:18]=[N:19][N:20]=1)(=[O:14])=[O:13])[CH2:7]2.P([O-])([O-])([O-])=O.[K+].[K+].[K+].[F:29][C:30]1[CH:31]=[C:32](B(O)O)[CH:33]=[CH:34][C:35]=1[F:36].Cl.O1[CH2:46][CH2:45][O:44][CH2:43]C1>O>[F:29][C:30]1[CH:31]=[C:32]([C:2]2[CH:3]=[CH:4][C:46]([C:2]3[CH:11]=[CH:10][CH:9]=[C:8]4[C:3]=3[CH2:4][CH2:5][N:6]([S:12]([NH:15][C:16]3[S:17][CH:18]=[N:19][N:20]=3)(=[O:14])=[O:13])[CH2:7]4)=[C:45]([O:44][CH3:43])[CH:11]=2)[CH:33]=[CH:34][C:35]=1[F:36]

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 312751,4-DioxaneHCID 62657Potassium Phosphate, TribasicHCID 27343373,4-Difluorobenzeneboronic acidHCID 89815510HCID 89815510, compound

Product 1

HCID 71737517HCID 71737517, compoundYield 35%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
150 °C

Procedure

A microwave vial charged with Pd(Amphos)2Cl2 (9.43 mg, 0.013 mmol), (4-chloro-2-methoxy)phenylboronic acid (0.050 g, 0.266 mmol), 5-bromo-N-(1,3,4-thiadiazol-2-yl)-3,4-dihydroisoquinoline-2(1H)-sulfonamide (0.100 g, 0.266 mmol), potassium phosphate (0.339 g, 1.599 mmol), 1.5 mL of dioxane and 0.25 mL of water was heated to 150° C. in the microwave for 30 minutes. (3,4-difluorophenyl)boronic acid (0.053 g, 0.333 mmol) and an additional portion of Pd(Amphos)2Cl2 (9.43 mg, 0.013 mmol) were added, and the reaction mixture was heated to 150° C. in the microwave for an additional 30 minutes. The aqueous layer was removed, and the reaction mixture was treated with HCl (4N in dioxane) (0.266 ml, 1.066 mmol). After stirring for 10 minutes, the reaction mixture was concentrated. Purification of the crude residue by reverse phase column chromatography [RediSep Gold C18, 10-100% (0.1% NH4OH in MeOH)/(0.1% NH4OH in water)] gave 5-(3′,4′-difluoro-3-methoxy-[1,1′-biphenyl]-4-yl)-N-(1,3,4-thiadiazol-2-yl)-3,4-dihydroisoquinoline-2(1H)-sulfonamide (0.048 g, 0.093 mmol, 35.0% yield). 1H NMR (MeCN-d3) δ: 8.31 (s, 1H), 7.65 (ddd, J=12.2, 7.8, 2.2 Hz, 1H), 7.52 (dddt, J=7.1, 4.3, 2.7, 1.2 Hz, 1H), 7.37 (dt, J=10.6, 8.5 Hz, 1H), 7.14-7.27 (m, 4H), 7.07-7.12 (m, 1H), 6.99-7.05 (m, 1H), 4.20-4.41 (m, 2H), 3.81 (s, 3H), 3.30-3.39 (m, 1H), 3.12-3.24 (m, 1H), 2.63-2.76 (m, 1H), 2.42-2.55 (m, 1H); (M+H)+=515.0.

Workup

  1. temperaturethe reaction mixture was heated to 150° C. in the microwave for an additional 30 minutes
  2. customThe aqueous layer was removed
  3. concentrationthe reaction mixture was concentrated
  4. customPurification of the crude residue by reverse phase column chromatography [RediSep Gold C18, 10-100% (0.1% NH4OH in MeOH)/(0.1% NH4OH in water)]

Sources & evidence

ORD record
ord-df27f7eb0ef64681853fc382a8a1caf1
Source dataset
uspto-grants-2015_06
Patent number
US09051311B2

Reaction notes

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