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Ammonia → tert-Butyl (3R)-4-[3-(2-{[2-(2-{2-[(tert-butoxycarbonyl)amino]ethoxy}-ethoxy)pyridin-3-yl]oxy}ethoxy)pyrazin-2-yl]-3-methylpiperazine-1-carboxylate

HRID 1765092
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HRID 1765092 반응식
O1CCCCC1[O:7][CH2:8][CH2:9][O:10][C:11]1[C:12]([O:17][CH2:18][CH2:19][O:20][CH2:21][CH2:22][NH:23][C:24](=[O:30])[O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[N:13][CH:14]=[CH:15][CH:16]=1.N.CC(C)([O-])C.[K+].Cl[C:39]1[C:40]([N:45]2[CH2:50][CH2:49][N:48]([C:51]([O:53][C:54]([CH3:57])([CH3:56])[CH3:55])=[O:52])[CH2:47][C@H:46]2[CH3:58])=[N:41][CH:42]=[CH:43][N:44]=1>CC(O)=O.[Cl-].[Na+].O.O.[Cl-].[Na+].O.C(#N)C>[C:26]([O:25][C:24]([NH:23][CH2:22][CH2:21][O:20][CH2:19][CH2:18][O:17][C:12]1[C:11]([O:10][CH2:9][CH2:8][O:7][C:39]2[C:40]([N:45]3[CH2:50][CH2:49][N:48]([C:51]([O:53][C:54]([CH3:57])([CH3:56])[CH3:55])=[O:52])[CH2:47][C@H:46]3[CH3:58])=[N:41][CH:42]=[CH:43][N:44]=2)=[CH:16][CH:15]=[CH:14][N:13]=1)=[O:30])([CH3:29])([CH3:28])[CH3:27]
참가 물질반응 조건실험 절차후처리출처 및 근거반응 노트

참가 물질

9

반응물 4

HCID 222AmmoniaHCID 23665647Potassium tert-butoxideHCID 86591089tert-Butyl {2-[2-({3-[2-(tetrahydro-2H-pyran-2-yloxy)ethoxy]pyridin-2-yl}oxy)ethoxy]ethyl}carbamateHCID 86591091(R)-tert-butyl 4-(3-chloropyrazin-2-yl)-3-methylpiperazine-1-carboxylate

생성물 1

HCID 86591090tert-Butyl (3R)-4-[3-(2-{[2-(2-{2-[(tert-butoxycarbonyl)amino]ethoxy}-ethoxy)pyridin-3-yl]oxy}ethoxy)pyrazin-2-yl]-3-methylpiperazine-1-carboxylate
수율 40.9%

시약·촉매·용매 4

HCID 176Acetic Acid용매HCID 6342Acetonitrile용매HCID 23713072Sodium chloride dihydrate용매HCID 57417360Sodium chloride; water용매

반응 조건

온도
50 °C

실험 절차

tert-Butyl {2-[2-({3-[2-(tetrahydro-2H-pyran-2-yloxy)ethoxy]pyridin-2-yl}oxy)ethoxy]ethyl}carbamate (from Step 1; 0.74 g, 1.7 mmol) was suspended in 2 M HOAc (5 mL) and acetonitrile (1 mL) and heated at 50° C. for two days. The solution was neutralized with concentrated aqueous ammonia. Brine was added (3 mL) and the mixture was extracted with CHCl3 (×3). The combined organic phases were dried (MgSO4) and the solvent was removed under reduced pressure. The remaining oil was dissolved in dry DMSO (10 mL), potassium tert-butoxide (0.36 g, 3.2 mmol) was added followed by tert-butyl (3R)-4-(3-chloropyrazin-2-yl)-3-methylpiperazine-1-carboxylate (from Example 5; 0.59 g, 1.9 mmol) and the mixture was heated at 50° C. for 20 minutes. The reaction mixture was diluted with water/brine (90:10) and extracted with CHCl3 (×3). The combined organic phases were dried (MgSO4), the solvent was removed under reduced pressure and the remaining oil was chromatographed on a column of silica with hexane/EtOAc (70:30) as eluent to give 0.43 g (40%) of the title compound as a colorless oil. LC-UV purity: system (A) 100%. HRMS m/z calcd for C30H46N6O8 (M)+ 618.3377. found 618.3381. Step 3: {2-[2-({3-[2-({3-[(2R)-2-Methylpiperazin-1-yl]pyrazin-2-yl}oxy)ethoxy]pyridin-2-yl}oxy)ethoxy]ethyl}amine, bis(trifluoroacetate).

후처리

  1. extractionthe mixture was extracted with CHCl3 (×3)
  2. dry with materialThe combined organic phases were dried (MgSO4)
  3. customthe solvent was removed under reduced pressure
  4. dissolutionThe remaining oil was dissolved in dry DMSO (10 mL)
  5. extractionextracted with CHCl3 (×3)
  6. dry with materialThe combined organic phases were dried (MgSO4)
  7. customthe solvent was removed under reduced pressure
  8. customthe remaining oil was chromatographed on a column of silica with hexane/EtOAc (70:30) as eluent

출처 및 근거

ORD 기록
ord-ac43c76598564435954e6bf2c483f564
출처 데이터셋
uspto-grants-2007_06
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US07226925B2

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