Acetic Acid → 3'-(4-Fluorophenyl)-4-[2-(3-isobutyl-5-methyl-1-pyridin-2-yl-1H-pyrazol-4-yl)-ethyl]-3,4,5,6-tetrahydro-2H-[1,2']bipyrazine hydrochloride

HRID 220505노트

반응식

HRID 220505 반응식
[CH2:1]([C:5]1[C:9]([CH2:10][CH:11]=O)=[C:8]([CH3:13])[N:7]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][N:15]=2)[N:6]=1)[CH:2]([CH3:4])[CH3:3].[F:20][C:21]1[CH:26]=[CH:25][C:24]([C:27]2[C:28]([N:33]3[CH2:38][CH2:37][NH:36][CH2:35][CH2:34]3)=[N:29][CH:30]=[CH:31][N:32]=2)=[CH:23][CH:22]=1.C(O)(=O)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C(Cl)[Cl:58]>>[ClH:58].[F:20][C:21]1[CH:26]=[CH:25][C:24]([C:27]2[C:28]([N:33]3[CH2:34][CH2:35][N:36]([CH2:11][CH2:10][C:9]4[C:5]([CH2:1][CH:2]([CH3:4])[CH3:3])=[N:6][N:7]([C:14]5[CH:19]=[CH:18][CH:17]=[CH:16][N:15]=5)[C:8]=4[CH3:13])[CH2:37][CH2:38]3)=[N:29][CH:30]=[CH:31][N:32]=2)=[CH:23][CH:22]=1

참가 물질

6

반응물 5

HCID 176Acetic AcidHCID 6344DichloromethaneHCID 5049666Sodium triacetoxyborohydrideHCID 673669592-(4-Fluorophenyl)-3-(piperazin-1-yl)pyrazineHCID 86641652(3-Isobutyl-5-methyl-1-pyridin-2-yl-1H-pyrazol-4-yl)-acetaldehyde

생성물 1

HCID 685945743'-(4-Fluorophenyl)-4-[2-(3-isobutyl-5-methyl-1-pyridin-2-yl-1H-pyrazol-4-yl)-ethyl]-3,4,5,6-tetrahydro-2H-[1,2']bipyrazine hydrochloride수율 50%

실험 절차

Combine (3-isobutyl-5-methyl-1-pyridin-2-yl-1H-pyrazol-4-yl)-acetaldehyde (0.21 g, 0.82 mmol), 3′-(4-fluorophenyl)-3,4,5,6-tetrahydro-2H-[1,2′]bipyrazinyl (0.21 g, 0.82 mmol) in DCM (10 mL) and stir at room temperature for 15 min. Add glacial acetic acid (0.07 mL, 1.23 mmol) then sodium triacetoxyborohydride (0.26 g, 1.23 mmol). Stir at room temperature for 20 hr. Concentrate, then purify using SCX chromatography and further purify using silica gel chromatography, eluting with 5% 7 M ammonia in methanol:DCM. Dissolve the free base in methanol (5 mL) and treat with ammonium chloride (0.022 g). Concentrate the resulting solution to give the title compound as a white powder (0.22 g, 50%). MS: m/z=500.3 [M+H]+.

후처리

  1. concentrationConcentrate
  2. custompurify
  3. customfurther purify
  4. washeluting with 5% 7 M ammonia in methanol
  5. dissolutionDissolve the free base in methanol (5 mL)
  6. additiontreat with ammonium chloride (0.022 g)
  7. concentrationConcentrate the resulting solution

출처 및 근거

ORD 기록
ord-3118001bfa0546168184abf0e0c093a0
출처 데이터셋
uspto-grants-2012_06
특허 번호
US08202873B2

반응 노트

불러오는 중…