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

HRID 553510노트

반응식

HRID 553510 반응식
[ClH:1].Cl.[CH3:3][O:4][CH2:5][C:6]1[CH:11]=[CH:10][C:9]([C:12]2[C:13]([N:18]3[CH2:23][CH2:22][NH:21][CH2:20][CH2:19]3)=[N:14][CH:15]=[CH:16][N:17]=2)=[CH:8][CH:7]=1.[OH-].[Na+].[CH3:26][N:27]([CH2:37][CH:38]=O)[S:28]([C:31]1[CH:32]=[N:33][N:34]([CH3:36])[CH:35]=1)(=[O:30])=[O:29].C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCCl>[ClH:1].[CH3:3][O:4][CH2:5][C:6]1[CH:11]=[CH:10][C:9]([C:12]2[C:13]([N:18]3[CH2:23][CH2:22][N:21]([CH2:38][CH2:37][N:27]([CH3:26])[S:28]([C:31]4[CH:32]=[N:33][N:34]([CH3:36])[CH:35]=4)(=[O:30])=[O:29])[CH2:20][CH2:19]3)=[N:14][CH:15]=[CH:16][N:17]=2)=[CH:8][CH:7]=1

참가 물질

6

반응물 4

HCID 14798Sodium Hydroxide2회HCID 5049666Sodium triacetoxyborohydrideHCID 685945563'-(4-methoxymethyl-phenyl)-3,4,5,6-tetrahydro-2H-[1,2']bipyrazinyl dihydrochlorideHCID 866402111-Methyl-1H-pyrazole-4-sulfonic acid methyl-(2-oxo-ethyl)-amide

생성물 1

HCID 673671031-Methyl-1h-pyrazole-4-sulfonic acid {2-[3'-(4-methoxymethyl-phenyl)-2,3,5,6-tetrahydro-[1,2']bipyrazinyl-4-yl]-ethyl}-methyl-amide hydrochloride수율 93%

시약·촉매·용매 1

HCID 111,2-Dichloroethane용매2회

반응 조건

온도
7.5 °C

실험 절차

Cool a suspension of 3′-(4-methyoxymethyl-phenyl)-3,4,5,6-tetrahydro-2H-[1,2′]bipyrazinyl dihydrochloride (23.62 g, 66.11 mmol) in 1,2-dichloroethane (500 mL) at 5° C. Treat with 1.0 M NaOH (141 mL, 141 mmol), separate layers, dry the organics over Na2SO4, filter, then add to a solution of 1-methyl-1H-pyrazole-4-sulfonic acid methyl-(2-oxo-ethyl)-amide (17.66 g, 81.29 mmol) in 1,2-dichloroethane (1 L). Cool the reaction mixture to 5-10° C., treat with sodium triacetoxyborohydride (29.50 g, 132.2 mmol), and stir at room temperature overnight. Recool the reaction to 5° C., treat with 5 M NaOH (200 mL), and separate the resulting layers. Extract the aqueous layer with CH2Cl2 (500 mL), combine the organics, dry over Na2SO4, filter and concentrate. Dissolve the crude material in MeOH/EtOAc, treat with activated carbon (50 g) at room temperature for 1 hr., then filter through celite and concentrate to provide the free base of the title compound as an oil (29.8 g, 93%). Cool anhydrous EtOH (100 mL) to 5° C. and then add dropwise acetyl chloride (4.45 mL, 61.39 mmol). Stir the resulting solution at room temperature for about 15 min., then add it dropwise to a solution of the above free base dissolved in anhydrous EtOH (800 mL). Stir at room temperature for 0.5 hr., then concentrate in vacuo to ca. 20% of the original volume. Treat the resulting oil/solid with EtOAc (1.5 L). Recover the resulting yellow solid by vacuum filtration and dry in vacuo to provide the title compound (27.28 g, 85.2%). MS ES: m/z=486 [M+H]+.

후처리

  1. temperatureCool
  2. customseparate layers
  3. dry with materialdry the organics over Na2SO4
  4. filtrationfilter
  5. customthe reaction to 5° C.
  6. customseparate the resulting layers
  7. extractionExtract the aqueous layer with CH2Cl2 (500 mL)
  8. dry with materialdry over Na2SO4
  9. filtrationfilter
  10. concentrationconcentrate
  11. dissolutionDissolve the crude material in MeOH/EtOAc
  12. additiontreat with activated carbon (50 g) at room temperature for 1 hr
  13. filtration, then filter through celite
  14. concentrationconcentrate

출처 및 근거

ORD 기록
ord-f42e07f2c71d46a5a4123b5a93f2fdfc
출처 데이터셋
uspto-grants-2011_11
특허 번호
US08048884B2

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