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Hydrochloric Acid → 1-(2-methoxy-4-(thiazol-2-yl)phenyl)-N-(pyrimidin-4-yl)isoquinoline-6-sulfonamide

HRID 1473626
ノート
印刷プレビュー

反応式

HRID 1473626 の反応式
[CH3:1][O:2][C:3]1[CH:4]=[C:5]([C:18]2[S:19][CH:20]=[CH:21][N:22]=2)[CH:6]=[CH:7][C:8]=1B1OC(C)(C)C(C)(C)O1.Cl[C:24]1[C:33]2[C:28](=[CH:29][C:30]([S:34]([NH:37][C:38]3[CH:43]=[CH:42][N:41]=[CH:40][N:39]=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.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>[CH3:1][O:2][C:3]1[CH:4]=[C:5]([C:18]2[S:19][CH:20]=[CH:21][N:22]=2)[CH:6]=[CH:7][C:8]=1[C:24]1[C:33]2[C:28](=[CH:29][C:30]([S:34]([NH:37][C:38]3[CH:43]=[CH:42][N:41]=[CH:40][N:39]=3)(=[O:35])=[O:36])=[CH:31][CH:32]=2)[CH:27]=[CH:26][N:25]=1
参加物実験手順後処理出典と根拠反応ノート

参加物

7

反応物 4

HCID 313Hydrochloric AcidHCID 11430Potassium CarbonateHCID 866876591-chloro-N-(pyrimidin-4-yl)isoquinoline-6-sulfonamideHCID 866876962-(3-Methoxy-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)thiazole

生成物 1

HCID 866876951-(2-methoxy-4-(thiazol-2-yl)phenyl)-N-(pyrimidin-4-yl)isoquinoline-6-sulfonamide収率 68.4%

試薬・触媒・溶媒

2
HCID 178418807HCID 178418807、化合物触媒HCID 312751,4-Dioxane溶媒

実験手順

A solution of PdCl2(dppf)-CH2Cl2 adduct (0.127 g, 0.156 mmol), 2-(3-methoxy-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)thiazole (Intermediate OOOOO; 0.643 g, 2.026 mmol), 1-chloro-N-(pyrimidin-4-yl)isoquinoline-6-sulfonamide (Intermediate GG) (0.500 g, 1.559 mmol), and potassium carbonate (0.862 g, 6.24 mmol) in 6 mL dioxane/2 mL water was heated to 110° C. for 2 hours. LC/MS showed mostly 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) (1.559 ml, 6.24 mmol). After stirring for an additional 10 minutes, 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-(2-methoxy-4-(thiazol-2-yl)phenyl)-N-(pyrimidin-4-yl)isoquinoline-6-sulfonamide (0.507 g, 1.066 mmol, 68.4% yield). 1H NMR (MeCN-d3) δ: 8.71 (d, J=5.7 Hz, 1H), 8.63 (s, 1H), 8.48 (s, 1H), 8.21 (d, J=6.3 Hz, 1H), 7.91-7.97 (m, 3H), 7.75-7.84 (m, 2H), 7.72 (sd, J=7.8 Hz, 1H), 7.60 (d, J=3.2 Hz, 1H), 7.45 (d, J=7.8 Hz, 1H), 7.06 (s, J=6.3 Hz, 1H), 3.75 (s, 3H); (M+H)+=476.0.

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 [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-f690837bd5c04398bbf83cd9d868732d
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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