Hydrochloric Acid → HCID 86687704, compound

HRID 1473633Notes

Reaction equation

HRID 1473633 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1B(O)O.Cl[C:13]1[CH:18]=[CH:17][C:16]([C:19]2[C:28]3[C:23](=[CH:24][C:25]([S:29]([NH:32][C:33]4[CH:38]=[CH:37][N:36]=[CH:35][N:34]=4)(=[O:31])=[O:30])=[CH:26][CH:27]=3)[CH:22]=[CH:21][N:20]=2)=[C:15]([O:39][CH3:40])[CH:14]=1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].Cl>O.O1CCOCC1>[CH3:1][O:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[C:13]1[CH:18]=[CH:17][C:16]([C:19]2[C:28]3[C:23](=[CH:24][C:25]([S:29]([NH:32][C:33]4[CH:38]=[CH:37][N:36]=[CH:35][N:34]=4)(=[O:30])=[O:31])=[CH:26][CH:27]=3)[CH:22]=[CH:21][N:20]=2)=[C:15]([O:39][CH3:40])[CH:14]=1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 62657Potassium Phosphate, TribasicHCID 27339582-Methoxyphenylboronic acidHCID 866874841-(4-chloro-2-methoxyphenyl)-N-(pyrimidin-4-yl)isoquinoline-6-sulfonamide

Product 1

HCID 86687704HCID 86687704, compoundYield 24%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
150 °C

Procedure

A microwave vial charged with Pd(Amphos)2Cl2 (0.008 g, 0.012 mmol), 2-methoxyphenylboronic acid (0.036 g, 0.234 mmol), 1-(4-chloro-2-methoxyphenyl)-N-(pyrimidin-4-yl)isoquinoline-6-sulfonamide (From example 160; 0.050 g, 0.117 mmol), potassium phosphate (0.099 g, 0.469 mmol), 1.5 mL dioxane, and 0.25 mL water was heated to 150° C. in the microwave for 30 minutes. LC/MS showed mostly product, so the aqueous layer was removed and the reaction mixture was treated with HCl (4N in dioxane) (117 μl, 0.469 mmol). After stirring for 10 minutes, the reaction mixture was concentrated. The crude residue was purified by [PREP LC/MS-2 System Column: XBridge 19×100 mm 12230326114 03 Mobile phase: 0.1% NH4OH in water/acetonitrile Flow rate: 40 ml/min Inj: 2200 uL. Gradient: 10 min10-40%_LV_NH3] yielding 1-(2′,3-dimethoxy-[1,1′-biphenyl]-4-yl)-N-(pyrimidin-4-yl)isoquinoline-6-sulfonamide (0.014 g, 0.028 mmol, 24.0%). 1H NMR (500 MHz, DMSO-d6) δ ppm 3.67 (s, 3H) 3.79-3.88 (m, 3H) 6.99-7.13 (m, 2H) 7.17 (d, J=8.12 Hz, 1H) 7.22-7.32 (m, 2H) 7.32-7.48 (m, 3H) 7.81 (d, J=8.76 Hz, 1H) 7.98 (d, J=9.03 Hz, 1H) 8.09 (d, J=5.61 Hz, 1H) 8.26 (br. s., 1H) 8.58 (s, 1H) 8.61-8.72 (m, 2H); (M+H)+=499.3.

Workup

  1. customso the aqueous layer was removed
  2. concentrationthe reaction mixture was concentrated
  3. customThe crude residue was purified by [PREP LC/MS-2 System Column: XBridge 19×100 mm 12230326114 03 Mobile phase: 0.1% NH4OH in water/acetonitrile Flow rate: 40 ml/min Inj: 2200 uL. Gradient: 10 min10-40%_LV_NH3]

Sources & evidence

ORD record
ord-9c9ed36e4d864784947c9791d522f7e1
Source dataset
uspto-grants-2015_04
Patent number
US09012443B2

Reaction notes

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