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Hydrochloric Acid → 1-(4'-chloro-2',3-dimethoxy-[1,1'-biphenyl]-4-yl)-N-(pyrimidin-4-yl)isoquinoline-6-sulfonamide

HRID 1473629
Notes
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Reaction equation

HRID 1473629 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5](B(O)O)=[C:4]([O:11][CH3:12])[CH:3]=1.Cl[C:14]1[C:23]2[C:18](=[CH:19][C:20]([S:24]([NH:27][C:28]3[CH:33]=[CH:32][N:31]=[CH:30][N:29]=3)(=[O:26])=[O:25])=[CH:21][CH:22]=2)[CH:17]=[CH:16][N:15]=1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].Cl>O1CCOCC1>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:2]2[CH:7]=[CH:6][C:5]([C:14]3[C:23]4[C:18](=[CH:19][C:20]([S:24]([NH:27][C:28]5[CH:33]=[CH:32][N:31]=[CH:30][N:29]=5)(=[O:26])=[O:25])=[CH:21][CH:22]=4)[CH:17]=[CH:16][N:15]=3)=[C:4]([O:11][CH3:12])[CH:3]=2)=[C:4]([O:11][CH3:12])[CH:3]=1
ParticipantsProcedureWorkupSources & evidenceReaction notes

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 62657Potassium Phosphate, TribasicHCID 3858606(4-Chloro-2-methoxyphenyl)boronic acidHCID 866876591-chloro-N-(pyrimidin-4-yl)isoquinoline-6-sulfonamide

Product 1

HCID 866877001-(4'-chloro-2',3-dimethoxy-[1,1'-biphenyl]-4-yl)-N-(pyrimidin-4-yl)isoquinoline-6-sulfonamideYield 4%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

A solution of Pd(Amphos)2Cl2 (0.442 g, 0.624 mmol), (4-chloro-2-methoxyphenyl)boronic acid (1.278 g, 6.86 mmol), 1-chloro-N-(pyrimidin-4-yl)isoquinoline-6-sulfonamide (2.000 g, 6.24 mmol), and potassium phosphate (5.29 g, 24.94 mmol) in 30 mL dioxane/12 mL water was heated to 110° C. for 2 hours. LC/MS showed product, so the reaction mixture was allowed to cool to room temperature. The aqueous layer was removed, and the reaction mixture was treated with HCl (4N in dioxane) (6.24 ml, 24.94 mmol). After stirring for 10 minutes, the reaction mixture was concentrated. Purification of the crude residue by reverse phase column chromatography [RediSep Gold C18, 10-100% (0.1% NH4OH in MeOH)/(0.1% NH4OH in water)] gave 1-(4′-chloro-2′,3-dimethoxy-[1,1′-biphenyl]-4-yl)-N-(pyrimidin-4-yl)isoquinoline-6-sulfonamide (0.073 g, 0.137 mmol, 2.197% yield). 1H NMR (MeCN-d3) δ: 8.69 (m, 1H), 8.62 (s, 1H), 8.44-8.52 (m, 1H), 8.21 (d, J=6.4 Hz, 1H), 7.89-7.99 (m, 2H), 7.81 (d, J=9.0 Hz, 1H), 7.42 (m, 1H), 7.32-7.39 (m, 1H), 7.29 (s, 1H), 7.24 (m, 1H), 7.16 (d, 1H), 7.03-7.12 (m, 2H), 3.84-3.88 (m, 3H), 3.64-3.67 (m, 3H); (M+H)+=533.0.

Workup

  1. customThe aqueous layer was removed
  2. concentrationthe reaction mixture was concentrated
  3. customPurification of the crude residue by reverse phase column chromatography [RediSep Gold C18, 10-100% (0.1% NH4OH in MeOH)/(0.1% NH4OH in water)]

Sources & evidence

ORD record
ord-75657fec9eac499b86e77792c35fe5a5
Source dataset
uspto-grants-2015_04
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US09012443B2

Reaction notes

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