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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
ノート
印刷プレビュー

反応式

HRID 1473629 の反応式
[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
参加物実験手順後処理出典と根拠反応ノート

参加物

6

反応物 4

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

生成物 1

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

試薬・触媒・溶媒 1

HCID 312751,4-Dioxane溶媒

実験手順

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.

後処理

  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)]

出典と根拠

ORDレコード
ord-75657fec9eac499b86e77792c35fe5a5
出典データセット
uspto-grants-2015_04
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US09012443B2

反応ノート

読み込み中…

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