Sodium Bicarbonate → 3'-(4-Methoxymethyl-phenyl)-4-(1,3-dimethyl-1H-pyrazol-4-ylmethyl)-3,4,5,6-tetrahydro-2H-[1,2']bipyrazinyl hydrochloride

HRID 220574노트

반응식

HRID 220574 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.[CH3:24][N:25]1[CH:29]=[C:28]([CH:30]=O)[C:27]([CH3:32])=[N:26]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C(=O)(O)[O-].[Na+]>O1CCCC1>[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]([CH2:30][C:28]4[C:27]([CH3:32])=[N:26][N:25]([CH3:24])[CH:29]=4)[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 516892Sodium BicarbonateHCID 8472851,3-dimethyl-1H-pyrazole-4-carbaldehydeHCID 5049666Sodium triacetoxyborohydrideHCID 685945563'-(4-methoxymethyl-phenyl)-3,4,5,6-tetrahydro-2H-[1,2']bipyrazinyl dihydrochloride

생성물 1

HCID 685952753'-(4-Methoxymethyl-phenyl)-4-(1,3-dimethyl-1H-pyrazol-4-ylmethyl)-3,4,5,6-tetrahydro-2H-[1,2']bipyrazinyl hydrochloride수율 22%

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매

실험 절차

Stir 3′-(4-methoxymethyl-phenyl)-3,4,5,6-tetrahydro-2H-[1,2′]bipyrazinyl dihydrochloride (312 mg, 0.87 mmol) in dry tetrahydrofuran (10 mL), and add 1,3-dimethyl-1H-pyrazole-4-carbaldehyde (138 mg, 0.87 mmol). Stir at room temperature for 15 min., and then add sodium triacetoxyborohydride (171 mg, 1.04 mmol). Stir the reaction for 17 hr. at room temperature, then at 50° C. for 20 hr. under nitrogen. Pour the reaction mixture into saturated aq. sodium bicarbonate (20 mL), extract with DCM (3×20 mL) and pass through an IST Phase Separator Frit®. Concentrate and purify using silica gel chromatography (eluting with 2:98 to 5:95 methanol:DCM). Dissolve the oil in acetonitrile and convert to the hydrochloride salt by adding 2 M aq HCl solution. Add water and lyophilize, then free base using an SCX-2® ion exchange cartridge. Further purify by low pH reverse phase HPLC. Form the free base by passing through an SCX-2® ion exchange cartridge washing with methanol then eluting with 3 M ammonia in methanol and concentrate. Dissolve the solid in acetonitrile and convert to the hydrochloride salt by adding 2 M aq HCl solution. Add water and lyophilize to give the title compound as a bright yellow solid (80 mg, 22%). MS (ES): m/z=393 [M+H]+.

후처리

  1. stirringStir
  2. customthe reaction for 17 hr
  3. waitat room temperature, then at 50° C. for 20 hr
  4. extractionextract with DCM (3×20 mL)
  5. concentrationConcentrate
  6. custompurify
  7. washsilica gel chromatography (eluting with 2:98 to 5:95 methanol:DCM)
  8. dissolutionDissolve the oil in acetonitrile
  9. additionby adding 2 M aq HCl solution
  10. customFurther purify by low pH reverse phase HPLC
  11. washwashing with methanol
  12. washthen eluting with 3 M ammonia in methanol
  13. concentrationconcentrate
  14. dissolutionDissolve the solid in acetonitrile
  15. additionby adding 2 M aq HCl solution

출처 및 근거

ORD 기록
ord-5e18ea97f31646cfa83bd7a65f63add3
출처 데이터셋
uspto-grants-2012_06
특허 번호
US08202873B2

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