Water → tert-butyl 2-(3-carbamoyl-1H-pyrazolo[3,4-c]pyridin-1-yl)acetate

HRID 1527290노트

반응식

HRID 1527290 반응식
I[C:2]1[C:10]2[C:5](=[CH:6][N:7]=[CH:8][CH:9]=2)[N:4]([CH2:11][C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13])[N:3]=1.O.C[N:21]([CH:23]=[O:24])C>CCOC(C)=O.[C-]#N.[C-]#N.[Zn+2].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].C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[C:23]([C:2]1[C:10]2[C:5](=[CH:6][N:7]=[CH:8][CH:9]=2)[N:4]([CH2:11][C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13])[N:3]=1)(=[O:24])[NH2:21]

참가 물질

8

반응물 3

HCID 962WaterHCID 6228DimethylformamideHCID 68283649Tert-butyl 2-(3-iodo-1H-pyrazolo[3,4-c]pyridin-1-yl)acetate

생성물 1

HCID 68284362tert-butyl 2-(3-carbamoyl-1H-pyrazolo[3,4-c]pyridin-1-yl)acetate

시약·촉매·용매 4

HCID 11186Zinc cyanide (Zn(CN)2)촉매HCID 9811564Bis(dibenzylideneacetone)palladium촉매HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)촉매HCID 8857Ethyl Acetate용매

반응 조건

온도
100 °C

실험 절차

A mixture of tert-butyl 2-(3-iodo-1H-pyrazolo[3,4-c]pyridin-1-yl)acetate (3.76 g, 10.5 mmol), Zn(CN)2 (1.35 g, 11.5 mmol), Pd(dppf)Cl2 (855 mg, 1.05 mmol), Pd2(dba)3 (959 mg, 1.05 mmol), water (4 mL) and DMF (30 mL) was stirred at 100° C. for 16 h under argon. The reaction mixture was diluted with EtOAc and then was successively washed with water, sat. aq. NaHCO3 (2×) and brine, dried (Phase separator) and concentrated under vacuum. The residual oil was purified by flash column chromatography on silica gel (EtOAc/c-hexane 1:1 then 100% EtOAc). MS (LC/MS): 259.0 [M+H]+; tR (HPLC conditions k): 3.10 min. Further elution of the column with CH2Cl2/MeOH 8:2 and subsequent purification by preparative HPLC (Macherey-Nagel Nucleosil 100-10 C18, 5 μm, 40×250 mm, flow: 40 mL/min, eluent: 5-100% CH3CN/H2O/20 min, 100% CH3CN/2 min, CH3CN and H2O containing 0.1% TFA) afforded tert-butyl 2-(3-carbamoyl-1H-pyrazolo[3,4-c]pyridin-1-yl)acetate as a side-product. MS (LC/MS): 277.0 [M+H]+; tR (HPLC conditions k): 2.39 min.

후처리

  1. washwas successively washed with water, sat. aq. NaHCO3 (2×) and brine
  2. customdried (Phase separator)
  3. concentrationconcentrated under vacuum
  4. customThe residual oil was purified by flash column chromatography on silica gel (EtOAc/c-hexane 1:1
  5. custom3.10 min
  6. washFurther elution of the column
  7. customwith CH2Cl2/MeOH 8:2 and subsequent purification by preparative HPLC (Macherey-Nagel Nucleosil 100-10 C18, 5 μm, 40×250 mm, flow: 40 mL/min, eluent: 5-100% CH3CN/H2O/20 min, 100% CH3CN/2 min, CH3CN and H2O containing 0.1% TFA)

출처 및 근거

ORD 기록
ord-649446bef7904659a60907c55b9d8437
출처 데이터셋
uspto-grants-2015_07
특허 번호
US09085555B2

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