Potassium Carbonate → 1-(6-chloro-2-methoxypyridin-3-yl)-N-(4-methoxybenzyl)-N-(pyrimidin-4-yl)isoquinoline-6-sulfonamide

HRID 1473573Notes

Reaction equation

HRID 1473573 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[N:37]=[C:36]([O:38][CH3:39])[C:35](B(O)O)=[CH:34][CH:33]=1.C(=O)([O-])[O-].[K+].[K+]>CCOC(C)=O.CCCCCCC>[Cl:31][C:32]1[N:37]=[C:36]([O:38][CH3:39])[C:35]([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:34][CH:33]=1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 467389286-Chloro-2-methoxypyridine-3-boronic acidHCID 866876191-chloro-N-(4-methoxybenzyl)-N-(pyrimidin-4-yl)isoquinoline-6-sulfonamide

Product 1

HCID 866876341-(6-chloro-2-methoxypyridin-3-yl)-N-(4-methoxybenzyl)-N-(pyrimidin-4-yl)isoquinoline-6-sulfonamideYield 97%

Reagents, catalysts & solvents 1

HCID 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, 97 mg, 0.220 mmol), (6-chloro-2-methoxypyridin-3-yl)boronic acid (45.3 mg, 0.242 mmol), potassium carbonate (91 mg, 0.660 mmol), and pd(ph3p)4 (12.71 mg, 0.011 mmol). The vial was flushed with Ar (g), then 1,4-dioxane (825 μl) and water (275 μl) were added. The vial was sealed and heated to 80° C. for 45 min in a Biotage Initiator microwave reactor. LCMS showed primarily the desired product. The mixture was extracted with EtOAc (3×), and the combined organic extracts were concentrated. The residue was purified by chromatography on silica gel (12-g Redi-Sep Gold column, 0-50% EtOAc/Heptane, then 50-100% EtOAc/Heptane) to give 1-(6-chloro-2-methoxypyridin-3-yl)-N-(4-methoxybenzyl)-N-(pyrimidin-4-yl)isoquinoline-6-sulfonamide (117 mg, 0.213 mmol, 97% yield) as a cream-colored foam. m/z (ESI) 548.2 (M+H)+.

Workup

  1. customThe vial was flushed with Ar (g)
  2. addition1,4-dioxane (825 μl) and water (275 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 (12-g Redi-Sep Gold column, 0-50% EtOAc/Heptane

Sources & evidence

ORD record
ord-0563893eadf44c4387b14be583877763
Source dataset
uspto-grants-2015_04
Patent number
US09012443B2

Reaction notes

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