Potassium Carbonate → 1-(4-hydroxy-2-methoxyphenyl)-N-(4-methoxybenzyl)-N-(pyrimidin-4-yl)isoquinoline-6-sulfonamide

HRID 1473570Notes

Reaction equation

HRID 1473570 reaction equation
Cl[C:2]1[C:11]2[C:6](=[CH:7][C:8]([S:12]([N:15]([CH2:22][C:23]3[CH:28]=[CH:27][C:26]([O:29][CH3:30])=[CH:25][CH:24]=3)[C:16]3[CH:21]=[CH:20][N:19]=[CH:18][N:17]=3)(=[O:14])=[O:13])=[CH:9][CH:10]=2)[CH:5]=[CH:4][N:3]=1.[CH3:31][O:32][C:33]1[CH:34]=[C:35]([OH:48])[CH:36]=[CH:37][C:38]=1B1OC(C)(C)C(C)(C)O1.C(=O)([O-])[O-].[K+].[K+]>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.CCOC(C)=O.CCCCCCC>[OH:48][C:35]1[CH:36]=[CH:37][C:38]([C:2]2[C:11]3[C:6](=[CH:7][C:8]([S:12]([N:15]([CH2:22][C:23]4[CH:28]=[CH:27][C:26]([O:29][CH3:30])=[CH:25][CH:24]=4)[C:16]4[CH:21]=[CH:20][N:19]=[CH:18][N:17]=4)(=[O:14])=[O:13])=[CH:9][CH:10]=3)[CH:5]=[CH:4][N:3]=2)=[C:33]([O:32][CH3:31])[CH:34]=1

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 573502983-Methoxy-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenolHCID 866876191-chloro-N-(4-methoxybenzyl)-N-(pyrimidin-4-yl)isoquinoline-6-sulfonamide

Product 1

HCID 1364090681-(4-hydroxy-2-methoxyphenyl)-N-(4-methoxybenzyl)-N-(pyrimidin-4-yl)isoquinoline-6-sulfonamideYield 64%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 21899848Ethylacetate heptaneSolvent

Conditions

Temperature
80 °C

Procedure

A vial was charged with 1-chloro-N-(4-methoxybenzyl)-N-(pyrimidin-4-yl)isoquinoline-6-sulfonamide (INTERMEDIATE ZZZZ, 122 mg, 0.277 mmol), 3-methoxy-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenol (138 mg, 0.553 mmol), potassium carbonate (191 mg, 1.384 mmol), and Pd(PPh3)4 (32.0 mg, 0.028 mmol). The vial was flushed with Ar (g), then 1,4-dioxane (1038 μl) and water (346 μl) were added. The vial was sealed and heated to 80° C. for 2 h in a Biotage Initiator microwave reactor. The mixture was extracted with EtOAc (3×), and the combined organic extracts were concentrated. The residue was purified by chromatography on silica gel (25-g Interchim column, 35-85% EtOAc/Heptane, then with 85-100% EtOAc/Heptane) to give 1-(4-hydroxy-2-methoxyphenyl)-N-(4-methoxybenzyl)-N-(pyrimidin-4-yl)isoquinoline-6-sulfonamide (93.6 mg, 0.177 mmol, 64.0% yield) as an off-white solid. m/z (ESI) 529.2 (M+H)+.

Workup

  1. customThe vial was flushed with Ar (g)
  2. addition1,4-dioxane (1038 μl) and water (346 μl) were added
  3. customThe vial was sealed
  4. extractionThe mixture was extracted with EtOAc (3×)
  5. concentrationthe combined organic extracts were concentrated
  6. customThe residue was purified by chromatography on silica gel (25-g Interchim column, 35-85% EtOAc/Heptane

Sources & evidence

ORD record
ord-eca8e7d21b684653854ef074f94ddd3a
Source dataset
uspto-grants-2015_04
Patent number
US09012443B2

Reaction notes

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