Hydrochloric Acid → 1-(4-(4-fluorophenoxy)-2-methoxyphenyl)-N-(pyrimidin-4-yl)isoquinoline-6-sulfonamide

HRID 1473631ノート

反応式

HRID 1473631 の反応式
C(P(C(C)(C)C)C1C(C)=C(C)C(C)=C(C)C=1C1C(C(C)C)=CC(C(C)C)=CC=1C(C)C)(C)(C)C.[F:35][C:36]1[CH:41]=[CH:40][C:39]([OH:42])=[CH:38][CH:37]=1.Cl[C:44]1[CH:49]=[CH:48][C:47]([C:50]2[C:59]3[C:54](=[CH:55][C:56]([S:60]([NH:63][C:64]4[CH:69]=[CH:68][N:67]=[CH:66][N:65]=4)(=[O:62])=[O:61])=[CH:57][CH:58]=3)[CH:53]=[CH:52][N:51]=2)=[C:46]([O:70][CH3:71])[CH:45]=1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].Cl>O1CCOCC1>[F:35][C:36]1[CH:41]=[CH:40][C:39]([O:42][C:44]2[CH:49]=[CH:48][C:47]([C:50]3[C:59]4[C:54](=[CH:55][C:56]([S:60]([NH:63][C:64]5[CH:69]=[CH:68][N:67]=[CH:66][N:65]=5)(=[O:61])=[O:62])=[CH:57][CH:58]=4)[CH:53]=[CH:52][N:51]=3)=[C:46]([O:70][CH3:71])[CH:45]=2)=[CH:38][CH:37]=1

参加物

7

反応物 5

HCID 313Hydrochloric AcidHCID 97324-FluorophenolHCID 62657Potassium Phosphate, TribasicHCID 11953610Di-tert-butyl[3,4,5,6-tetramethyl-2',4',6'-tris(propan-2-yl)-[1,1'-biphenyl]-2-yl]phosphaneHCID 866874841-(4-chloro-2-methoxyphenyl)-N-(pyrimidin-4-yl)isoquinoline-6-sulfonamide

生成物 1

HCID 866877021-(4-(4-fluorophenoxy)-2-methoxyphenyl)-N-(pyrimidin-4-yl)isoquinoline-6-sulfonamide収率 22.7%

試薬・触媒・溶媒 1

HCID 312751,4-Dioxane溶媒

反応条件

温度
135 °C

実験手順

A microwave vial charged with di-tert-butyl(2′,4′,6′-triisopropyl-3,4,5,6-tetramethyl-[1,1′-biphenyl]-2-yl)phosphine (0.017 g, 0.035 mmol), 4-fluorophenol (0.039 g, 0.351 mmol), 1-(4-chloro-2-methoxyphenyl)-N-(pyrimidin-4-yl)isoquinoline-6-sulfonamide (0.075 g, 0.176 mmol), potassium phosphate (0.149 g, 0.703 mmol), 1.5 mL dioxane was heated to 135° C. in the microwave for 30 minutes. LC/MS showed mostly product, so the reaction mixture was filtered through a 0.45 μm syringe filter and was treated with HCl (4N in dioxane) (0.176 ml, 0.703 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-(4-fluorophenoxy)-2-methoxyphenyl)-N-(pyrimidin-4-yl)isoquinoline-6-sulfonamide (0.020 g, 0.040 mmol, 22.65% yield). 1H NMR (MeCN-d3) δ: 8.68 (d, J=5.7 Hz, 1H), 8.62 (s, 1H), 8.48 (s, 1H), 8.23 (d, J=8.5 Hz, 1H), 7.88-7.98 (m, 2H), 7.83 (d, J=9.0 Hz, 1H), 7.25-7.33 (m, 1H), 7.13-7.21 (m, 4H), 7.08 (d, J=5.4 Hz, 1H), 6.83 (s, 1H), 6.62-6.69 (m, 1H), 3.60 (s, 3H); (M+H)+=503.0.

後処理

  1. filtrationso the reaction mixture was filtered through a 0.45 μm syringe
  2. filtrationfilter
  3. concentrationthe reaction mixture was concentrated
  4. 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-2d93b91a732742379e78c48631e198ef
出典データセット
uspto-grants-2015_04
特許番号
US09012443B2

反応ノート

読み込み中…