Potassium Carbonate → HCID 86687660, compound

HRID 1473597Notes

Reaction equation

HRID 1473597 reaction equation
Cl[C:2]1[C:11]2[C:6](=[CH:7][C:8]([S:12]([N:15](CC3C=CC(OC)=CC=3)[C:16]3[S:17][CH:18]=[CH:19][N:20]=3)(=[O:14])=[O:13])=[CH:9][CH:10]=2)[CH:5]=[CH:4][N:3]=1.C(=O)([O-])[O-].[K+].[K+].O1CCOCC1.[OH:42][C:43]([C:46]1[CH:51]=[CH:50][CH:49]=[CH:48][C:47]=1B(O)O)([CH3:45])[CH3:44]>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.O>[OH:42][C:43]([C:46]1[CH:51]=[CH:50][CH:49]=[CH:48][C:47]=1[C:2]1[C:11]2[C:6](=[CH:7][C:8]([S:12]([NH:15][C:16]3[S:17][CH:18]=[CH:19][N:20]=3)(=[O:13])=[O:14])=[CH:9][CH:10]=2)[CH:5]=[CH:4][N:3]=1)([CH3:45])[CH3:44]

Participants

7

Reactant 4

HCID 11430Potassium CarbonateHCID 312751,4-DioxaneHCID 55267384HCID 55267384, compoundHCID 866874151-Chloro-N-(4-methoxybenzyl)-N-(thiazol-2-YL)isoquinoline-6-sulfonamide

Product 1

HCID 86687660HCID 86687660, compoundYield 40%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolvent

Procedure

To a microwave vial charged with 1-chloro-N-(4-methoxybenzyl)-N-(thiazol-2-yl)isoquinoline-6-sulfonamide (Intermediate JJJ; 50 mg, 0.112 mmol), potassium carbonate (77 mg, 0.561 mmol) and Pd(Ph3P)4 (12.96 mg, 0.011 mmol) was added dioxane (561 μl), (2-(2-hydroxypropan-2-yl)phenyl)boronic acid (20.18 mg, 0.112 mmol) and Water (187 μl) and irradiated at 100° C. for 30 min affording conversion to desired product (˜40%) with starting material remaining. To the mixture was added additional boronate (50 ul) and Pd(Ph3P)4 (12.96 mg, 0.011 mmol) and irradiated another 30 min at 100° C. affording consumption of starting material and product as the primary species. The organic layer was decanted and the aqueous rinsed once with EtOAc and the organics combined and dried under reduced pressure. To the resulting oil was added DCM (2 ml) and TFA (0.6 ml) and the resulting solution stirred at room temperature. The mixture was dried under reduced pressure and purified with a 25 g HP spherical silica gel (15 μm spherical, Interchim) ramping DCM:MeOH (90:10) in DCM (0-100%) affording product as a yellow film which was lyophilized from MeOH/H2O affording a fluffy yellow solid 1-(2-(2-hydroxypropan-2-yl)phenyl)-N-(thiazol-2-yl)isoquinoline-6-sulfonamide 2,2,2-trifluoroacetate (39 mg, 0.072 mmol, 64.5% yield). 1H NMR (400 MHz, DMSO-d6) δ=12.92 (br. s., 1H), 8.67-8.55 (m, 2H), 8.27 (br. s., 1H), 7.94 (d, J=8.3 Hz, 1H), 7.77-7.65 (m, 2H), 7.56 (t, J=7.1 Hz, 1H), 7.38 (t, J=7.4 Hz, 1H), 7.29 (d, J=4.6 Hz, 1H), 7.21 (d, J=7.3 Hz, 1H), 6.89 (d, J=4.6 Hz, 1H), 1.37 (s, 3H), 1.24 (s, 4H). m/z (ESI) 426.0 (M+H)+

Workup

  1. customirradiated at 100° C. for 30 min

Sources & evidence

ORD record
ord-aaa81381e87e4bf180270c3a2d1d0268
Source dataset
uspto-grants-2015_04
Patent number
US09012443B2

Reaction notes

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