Potassium Carbonate → HCID 86687657, compound

HRID 1473594Notes

Reaction equation

HRID 1473594 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.[F:30][C:31]1[C:36](B(O)O)=[CH:35][C:34]([CH3:40])=[CH:33][N:32]=1.C(=O)([O-])[O-].[K+].[K+].O1CCOCC1>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>[F:30][C:31]1[C:36]([C:2]2[C:11]3[C:6](=[CH:7][C:8]([S:12]([NH:15][C:16]4[S:17][CH:18]=[CH:19][N:20]=4)(=[O:13])=[O:14])=[CH:9][CH:10]=3)[CH:5]=[CH:4][N:3]=2)=[CH:35][C:34]([CH3:40])=[CH:33][N:32]=1

Participants

7

Reactant 4

HCID 11430Potassium CarbonateHCID 312751,4-DioxaneHCID 447548582-Fluoro-5-methylpyridine-3-boronic acidHCID 866874151-Chloro-N-(4-methoxybenzyl)-N-(thiazol-2-YL)isoquinoline-6-sulfonamide

Product 1

HCID 86687657HCID 86687657, compound

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; 500 mg, 1.121 mmol), 2-fluoro-5-picoline-3-boronic acid (136 μl, 1.121 mmol), potassium carbonate (775 mg, 5.61 mmol) and Pd(Ph3P)4 (130 mg, 0.112 mmol) was added Dioxane (5606 μl) and Water (1869 μl) and irradiated at 100° C. for 30 mins affording ˜75% conversion to desired product as the primary species. Additional boronic acid (80 mg) and Pd(PPh3)4 (65 mg) was added and the mixture irradiated an additional 30 mins at 110° C. affording complete conversion to desired product. The organics were decanted, rinsed with EtOAc and the combined organics were dried under reduced pressure. The crude material was dissolved in DCM (3 ml) and TFA (1 ml) was added and the mixture stirred at room temperature for 2 hrs affording complete PMB cleavage. The crude material was purified with a 25 g Interchim column (25 μm spherical) ramping EtOAc in heptane (0-100%, then isocratic at 100% EtOAc, where product elutes, 10% DCM throughout) affording 1-(2-fluoro-5-methylpyridin-3-yl)-N-(thiazol-2-yl)isoquinoline-6-sulfonamide as a light yellow solid (377 mg, 0.941 mmol, 84% yield). 1H NMR (400 MHz, DMSO-d6) δ=12.89 (br. s., 1H), 8.74 (d, J=5.7 Hz, 1H), 8.60 (d, J=1.7 Hz, 1H), 8.26 (s, 1H), 8.21 (d, J=5.6 Hz, 1H), 8.02 (dd, J=2.3, 9.3 Hz, 1H), 7.97-7.91 (m, 1H), 7.91-7.85 (m, 1H), 7.28 (d, J=4.6 Hz, 1H), 6.87 (d, J=4.6 Hz, 1H), 2.40 (s, 3H). m/z (ESI) 401.2 (M+H)+

Workup

  1. customirradiated at 100° C. for 30 mins

Sources & evidence

ORD record
ord-c6c584ace20a4620b1343663a5d29410
Source dataset
uspto-grants-2015_04
Patent number
US09012443B2

Reaction notes

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