Hydrochloric Acid → 4-[N'-Methyl-N'-(2-methylsulfanyl-pyrimidine-4-carbonyl)-hydrazino]-piperidine-1-carboxylic acid tert-butyl ester

HRID 1838870노트

반응식

HRID 1838870 반응식
[CH3:1][N:2]([C:4]([C:6]1[CH:11]=[CH:10][N:9]=[C:8]([S:12][CH3:13])[N:7]=1)=[O:5])[NH2:3].[C:14]([O:18][C:19]([N:21]1[CH2:26][CH2:25][C:24](=O)[CH2:23][CH2:22]1)=[O:20])([CH3:17])([CH3:16])[CH3:15].[BH3-]C#N.[Na+].Cl.C(=O)(O)[O-].[Na+]>C(O)C>[C:14]([O:18][C:19]([N:21]1[CH2:26][CH2:25][CH:24]([NH:3][N:2]([CH3:1])[C:4]([C:6]2[CH:11]=[CH:10][N:9]=[C:8]([S:12][CH3:13])[N:7]=2)=[O:5])[CH2:23][CH2:22]1)=[O:20])([CH3:17])([CH3:15])[CH3:16]

참가 물질

7

반응물 5

HCID 313Hydrochloric AcidHCID 516892Sodium BicarbonateHCID 735900tert-Butyl 4-oxopiperidine-1-carboxylateHCID 5003444Sodium cyanoborohydrideHCID 591204582-Methylsulfanyl-pyrimidine-4-carboxylic acid N-methyl-hydrazide

생성물 1

HCID 698477704-[N'-Methyl-N'-(2-methylsulfanyl-pyrimidine-4-carbonyl)-hydrazino]-piperidine-1-carboxylic acid tert-butyl ester수율 68%

시약·촉매·용매 1

HCID 702Ethanol용매

실험 절차

To a stirred solution of 2-Methylsulfanyl-pyrimidine-4-carboxylic acid N-methyl-hydrazide, 15, (15 g, 75.8 mmol) in ethanol (60 mL) is added 4-oxo-piperidine-1-carboxylic acid tert-butyl ester (15.1 g, 75.8 mmol). The reaction mixture is refluxed for 1.5 hour, cooled to room temperature and NaCNBH3 (7.14 g, 113.7 mmol) added. The pH of the reaction mixture is adjusted to 3 with concentrated HCl and the reaction mixture stirred for 3 hours at room temperature. The mixture is neutralized with saturated sodium bicarbonate and extracted three times with CH2Cl2 and the combined organic layers are dried (MgSO4), filtered and concentrated in vacuo. Purification over silica (EtOAc) affords 19.7 g (68% yield) of the desired product. 1H NMR (300 MHz, CDCl3) δ 8.70 (q, J=2.9 Hz, 1H), 7.36-7.27 (m, 2H), 2.61 (s, 1H), 4.16 (q, J=6.9 Hz, 1H), 3.97-3.78 (m, 2H), 3.37 (d, J=16 Hz, 3H), 2.91-2.79 (m, 2H), 2.61 (s, 3H), 1.93-1.89 (m, 2H), 1.70-1.65 (m, 2H), 1.48 (d, J=8 Hz), 9H); ESI/MS: 382.3 (M+H).

후처리

  1. temperatureThe reaction mixture is refluxed for 1.5 hour
  2. extractionextracted three times with CH2Cl2
  3. dry with materialthe combined organic layers are dried (MgSO4)
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customPurification over silica (EtOAc)

출처 및 근거

ORD 기록
ord-b5a690cc633e422e89a7f8f838359086
출처 데이터셋
uspto-grants-2004_01
특허 번호
US06677337B2

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