1,2-Dimethoxyethane → 1-Methyl-1H-pyrazole-4-sulfonic acid {2-[3'-(4-cyanomethyl-phenyl)-2,3,5,6-tetrahydro-[1,2']bipyrazinyl-4-yl]-ethyl}-methyl-amide hydrochloride

HRID 553509노트

반응식

HRID 553509 반응식
[Cl:1][C:2]1[C:3]([N:8]2[CH2:13][CH2:12][N:11]([CH2:14][CH2:15][N:16]([CH3:26])[S:17]([C:20]3[CH:21]=[N:22][N:23]([CH3:25])[CH:24]=3)(=[O:19])=[O:18])[CH2:10][CH2:9]2)=[N:4][CH:5]=[CH:6][N:7]=1.COCCOC.[C:33]([CH2:35][C:36]1[CH:41]=[CH:40][C:39](B(O)O)=[CH:38][CH:37]=1)#[N:34].C(=O)([O-])[O-].[K+].[K+]>CC(N(C)C)=O.O.C(OCC)(=O)C.O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[ClH:1].[C:33]([CH2:35][C:36]1[CH:41]=[CH:40][C:39]([C:2]2[C:3]([N:8]3[CH2:13][CH2:12][N:11]([CH2:14][CH2:15][N:16]([CH3:26])[S:17]([C:20]4[CH:21]=[N:22][N:23]([CH3:25])[CH:24]=4)(=[O:19])=[O:18])[CH2:10][CH2:9]3)=[N:4][CH:5]=[CH:6][N:7]=2)=[CH:38][CH:37]=1)#[N:34]

참가 물질

9

반응물 4

HCID 80711,2-DimethoxyethaneHCID 11430Potassium CarbonateHCID 27733424-(Cyanomethyl)benzeneboronic acidHCID 866402031-Methyl-1H-pyrazole-4-sulfonic acid [2-(3'-chloro-2,3,5,6-tetrahydro-[1,2']bipyrazinyl-4-yl)-ethyl]-methyl-amide

생성물 1

HCID 673688301-Methyl-1H-pyrazole-4-sulfonic acid {2-[3'-(4-cyanomethyl-phenyl)-2,3,5,6-tetrahydro-[1,2']bipyrazinyl-4-yl]-ethyl}-methyl-amide hydrochloride수율 71%

시약·촉매·용매 4

HCID 178418397HCID 178418397, 화합물촉매HCID 962Water용매2회HCID 8857Ethyl Acetate용매HCID 21534740N,N-Dimethylacetamide--water (1/1)용매

반응 조건

온도
110 °C

실험 절차

Dissolve 1-methyl-1H-pyrazole-4-sulfonic acid [2-(3′-chloro-2,3,5,6-tetrahydro-[1,2′]bipyrazinyl-4-yl)-ethyl]-methyl-amide (0.250 g, 0.625 mmol) in DMA-H2O (or DME:H2O) (6 mL; 3:1 v/v, previously degassed with nitrogen). Add 4-cyanomethylphenyl boronic acid (0.121 g, 0.750 mmol), potassium carbonate (0.207 g, 1.500 mmol) and tetrakis(triphenylphosphine)palladium (0.036 g, 0.031 mmol). Stir the reaction mixture at 110° C. for 18 hr. Cool and dilute with ethyl acetate and water. Extract the aqueous layer with ethyl acetate and combine the organic layers. Dry the combined organic layers over sodium sulfate, filter, and concentrate. Purify by SCX chromatography, eluting with dichloromethane, dichloromethane:methanol 1:1, methanol, and 1N ammonia in methanol. Purify by silica gel chromatography eluting with hexanes:acetone 1:1 to afford the free base of the title compound (0.214 g, 71% yield).

후처리

  1. custom3:1 v/v, previously degassed with nitrogen)
  2. temperatureCool
  3. extractionExtract the aqueous layer with ethyl acetate
  4. dry with materialDry the combined organic layers over sodium sulfate
  5. filtrationfilter
  6. concentrationconcentrate
  7. customPurify by SCX chromatography
  8. washeluting with dichloromethane, dichloromethane:methanol 1:1, methanol, and 1N ammonia in methanol
  9. customPurify by silica gel chromatography
  10. washeluting with hexanes:acetone 1:1

출처 및 근거

ORD 기록
ord-acf2e4662d2345d7b20de649db1d2f69
출처 데이터셋
uspto-grants-2011_11
특허 번호
US08048884B2

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