Hydrochloric Acid → HCID 86687692、化合物

HRID 1473624ノート

反応式

HRID 1473624 の反応式
[F:1][CH:2]([F:22])[C:3]1[C:8]([O:9][CH3:10])=[CH:7][C:6](B2OC(C)(C)C(C)(C)O2)=[C:5]([O:20][CH3:21])[CH:4]=1.Cl[C:24]1[C:33]2[C:28](=[CH:29][C:30]([S:34]([N:37](CC3C=CC(OC)=CC=3)[C:38]3[S:39][CH:40]=[CH:41][N:42]=3)(=[O:36])=[O:35])=[CH:31][CH:32]=2)[CH:27]=[CH:26][N:25]=1.C(=O)([O-])[O-].[K+].[K+].Cl>O1CCOCC1.O.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].C(Cl)Cl>[F:22][CH:2]([F:1])[C:3]1[C:8]([O:9][CH3:10])=[CH:7][C:6]([C:24]2[C:33]3[C:28](=[CH:29][C:30]([S:34]([NH:37][C:38]4[S:39][CH:40]=[CH:41][N:42]=4)(=[O:36])=[O:35])=[CH:31][CH:32]=3)[CH:27]=[CH:26][N:25]=2)=[C:5]([O:20][CH3:21])[CH:4]=1

参加物

8

反応物 4

HCID 313Hydrochloric AcidHCID 11430Potassium CarbonateHCID 866874151-Chloro-N-(4-methoxybenzyl)-N-(thiazol-2-YL)isoquinoline-6-sulfonamideHCID 866876932-[4-(Difluoromethyl)-2,5-dimethoxyphenyl]-4,4,5,5-tetramethyl-1,3,2-dioxaborolane

生成物 1

HCID 86687692HCID 86687692、化合物収率 17.8%

試薬・触媒・溶媒 3

HCID 178418807HCID 178418807、化合物触媒HCID 962Water溶媒HCID 312751,4-Dioxane溶媒

実験手順

A solution of PdCl2(dppf)-CH2Cl2 adduct (7.78 mg, 9.53 μmol), 2-(4-(difluoromethyl)-2,5-dimethoxyphenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (Intermediate NNNNN; 0.078 g, 0.248 mmol), 1-chloro-N-(4-methoxybenzyl)-N-(thiazol-2-yl)isoquinoline-6-sulfonamide (Intermediate JJJ; 0.085 g, 0.191 mmol), and potassium carbonate (0.079 g, 0.572 mmol) in 2 mL dioxane, 1 mL water was heated to 100° C. overnight. LC/MS showed mostly product, so the reaction mixture was allowed to cool to room temperature. The aqueous layer was then removed. The reaction mixture was treated with HCl (4N in dioxane) (0.953 ml, 3.81 mmol) and was heated to 100° C. for one hour. LC/MS showed mostly product, so the reaction mixture was concentrated. Purification of the crude residue by reverse phase column chromatography [Puriflash C18 30μ, 10-100% (0.1% NH4OH in MeOH)/(0.1% NH4OH in water)] gave 1-(4-(difluoromethyl)-2,5-dimethoxyphenyl)-N-(thiazol-2-yl)isoquinoline-6-sulfonamide (0.016 g, 0.034 mmol, 17.58% yield). 1H NMR (MeCN-d3) δ: 8.68 (d, J=5.7 Hz, 1H), 8.51 (s, 1H), 7.93 (d, J=6.0 Hz, 1H), 7.87 (d, J=8.9 Hz, 1H), 7.73 (d, J=8.8 Hz, 1H), 7.32 (s, 1H), 7.10 (d, J=6.1 Hz, 1H), 6.99 (d, J=4.7 Hz, 1H), 6.61 (d, J=4.7 Hz, 1H), 3.81 (s, 3H), 3.65 (s, 3H); (M+H)+=478.0.

後処理

  1. customThe aqueous layer was then removed
  2. temperaturewas heated to 100° C. for one hour
  3. concentrationso the reaction mixture was concentrated
  4. customPurification of the crude residue by reverse phase column chromatography [Puriflash C18 30μ, 10-100% (0.1% NH4OH in MeOH)/(0.1% NH4OH in water)]

出典と根拠

ORDレコード
ord-a1f8e980ffca41a18c87856e307abb81
出典データセット
uspto-grants-2015_04
特許番号
US09012443B2

反応ノート

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