Potassium Carbonate → 1-(5-chloro-2-methoxyphenyl)-N-(4-methoxybenzyl)-N-(pyrimidin-4-yl)isoquinoline-6-sulfonamide

HRID 1473560Notes

Reaction equation

HRID 1473560 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.[Cl:31][C:32]1[CH:33]=[CH:34][C:35]([O:41][CH3:42])=[C:36](B(O)O)[CH:37]=1.C(=O)([O-])[O-].[K+].[K+]>CCOC(C)=O.CCCCCCC>[Cl:31][C:32]1[CH:37]=[CH:36][C:35]([O:41][CH3:42])=[C:34]([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:13])=[O:14])=[CH:9][CH:10]=3)[CH:5]=[CH:4][N:3]=2)[CH:33]=1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 27357515-Chloro-2-methoxyphenylboronic acidHCID 866876191-chloro-N-(4-methoxybenzyl)-N-(pyrimidin-4-yl)isoquinoline-6-sulfonamide

Product 1

HCID 866876201-(5-chloro-2-methoxyphenyl)-N-(4-methoxybenzyl)-N-(pyrimidin-4-yl)isoquinoline-6-sulfonamideYield 73.6%

Reagents, catalysts & solvents 1

HCID 21899848Ethylacetate heptaneSolvent

Conditions

Temperature
100 °C

Procedure

A vial was charged with 1-chloro-N-(4-methoxybenzyl)-N-(pyrimidin-4-yl)isoquinoline-6-sulfonamide (INTERMEDIATE ZZZZ; 100 mg, 0.227 mmol), (5-chloro-2-methoxyphenyl)boronic acid (63.4 mg, 0.340 mmol), potassium carbonate (94 mg, 0.680 mmol), and pd(ph3p)4 (26.2 mg, 0.023 mmol). The vial was flushed with Ar (g), then 1,4-dioxane (851 μl) and water (284 μl) were added. The vial was sealed and heated to 100° C. for 30 min 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 (40-g Redi-Sep Gold column, 0-40% EtOAc/Heptane, then 70% EtOAc/Heptane) to give 1-(5-chloro-2-methoxyphenyl)-N-(4-methoxybenzyl)-N-(pyrimidin-4-yl)isoquinoline-6-sulfonamide (91.2 mg, 0.167 mmol, 73.5% yield) as an off-white foam. m/z (ESI) 547.2 (M+H)+.

Workup

  1. customThe vial was flushed with Ar (g)
  2. addition1,4-dioxane (851 μl) and water (284 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 (40-g Redi-Sep Gold column, 0-40% EtOAc/Heptane

Sources & evidence

ORD record
ord-73e3025016bd4e5dbf74e734fdbfb6e5
Source dataset
uspto-grants-2015_04
Patent number
US09012443B2

Reaction notes

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