Hydrochloric Acid → HCID 86687692, 화합물

HRID 1473624노트

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HRID 1473624 반응식
[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

참가 물질

8

반응물 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

생성물 1

HCID 86687692HCID 86687692, 화합물수율 17.8%

시약·촉매·용매 3

HCID 178418807HCID 178418807, 화합물촉매HCID 962Water용매HCID 312751,4-Dioxane용매

실험 절차

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.

후처리

  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)]

출처 및 근거

ORD 기록
ord-a1f8e980ffca41a18c87856e307abb81
출처 데이터셋
uspto-grants-2015_04
특허 번호
US09012443B2

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