Nitric Acid → 4-(2-Amino-3-nitro-pyridin-4-yl)-piperazine-1-carboxylic acid tert-butyl ester

HRID 493109노트

반응식

HRID 493109 반응식
Cl[C:2]1[CH:7]=[CH:6][N:5]=[C:4]([NH2:8])[CH:3]=1.[N+:9]([O-:12])(O)=[O:10].C([O-])([O-])=O.[Na+].[Na+].[C:19]([O:23][C:24]([N:26]1[CH2:31][CH2:30][NH:29][CH2:28][CH2:27]1)=[O:25])([CH3:22])([CH3:21])[CH3:20].CCN(C(C)C)C(C)C>OS(O)(=O)=O.CS(C)=O.C(OCC)(=O)C.CCCCCC>[C:19]([O:23][C:24]([N:26]1[CH2:31][CH2:30][N:29]([C:2]2[CH:7]=[CH:6][N:5]=[C:4]([NH2:8])[C:3]=2[N+:9]([O-:12])=[O:10])[CH2:28][CH2:27]1)=[O:25])([CH3:22])([CH3:20])[CH3:21]

참가 물질

9

반응물 5

HCID 944Nitric AcidHCID 10340Sodium CarbonateHCID 81531DiisopropylethylamineHCID 143452tert-Butyl piperazine-1-carboxylateHCID 5818662-Amino-4-chloropyridine

생성물 1

HCID 576808314-(2-Amino-3-nitro-pyridin-4-yl)-piperazine-1-carboxylic acid tert-butyl ester수율 13%

시약·촉매·용매 3

HCID 679Dimethyl Sulfoxide용매HCID 1118Sulfuric Acid용매HCID 21226206Ethyl acetate hexane용매

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온도
0 °C

실험 절차

Following the procedure of Recl. Trav. Chim. Pays-Bas 88(11): 1263 (1969), 4-Chloro-pyridin-2-ylamine (A) (6.8 g, 67 mmol) was carefully dissolved in H2SO4 (45.2 ml) at 0° C. Nitric acid (2.3 ml) was added, maintaining the temperature at 0° C. The solution was stirred at 5° C. for 2 days. After it was judged complete by TLC (40% ethyl acetate/hexane), the mixture was carefully made basic with the addition of solid Na2CO3. The mixture was then extracted with ethyl acetate several times. The ethyl acetate was dried over magnesium sulfate and the solvents were removed under vacuum. The resulting crude was dissolved in DMSO (25 ml) with t-butyl-1-piperazine carboxylate (14.3 g, 75 mmol) and DIEA (10.3 g, 80 mmol). This mixture was heated to 50° C. for 3 hours before it was judged complete by MS. The mixture was purified by HPLC Method E to yield the title product 5 (2.8 g (13%), 8.6 mmol). 1H NMR (DMSO-d6): δ 7.82 (d, J=5.8 Hz, 1H), 6.98 (bs, 2H), 6.31 (d, J=5.8 Hz, 1H), 3.41 (m, 4H), 3.13 (m, 4H), 1.41 (s, 9H). MS (ESI-POS): [M+H]+=324.

후처리

  1. extractionThe mixture was then extracted with ethyl acetate several times
  2. dry with materialThe ethyl acetate was dried over magnesium sulfate
  3. customthe solvents were removed under vacuum
  4. temperatureThis mixture was heated to 50° C. for 3 hours before it
  5. customThe mixture was purified by HPLC Method E

출처 및 근거

ORD 기록
ord-5b4c7ddf50b94af585985b3af63181bc
출처 데이터셋
uspto-grants-2009_05
특허 번호
US07534796B2

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