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

HRID 1473626
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HRID 1473626 반응식
[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
참가 물질실험 절차후처리출처 및 근거반응 노트

참가 물질

7

반응물 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

생성물 1

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

시약·촉매·용매

2
HCID 178418807HCID 178418807, 화합물촉매HCID 312751,4-Dioxane용매

실험 절차

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.

후처리

  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)]

출처 및 근거

ORD 기록
ord-f690837bd5c04398bbf83cd9d868732d
출처 데이터셋
uspto-grants-2015_04
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US09012443B2

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