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

HRID 1838870ノート

反応式

HRID 1838870 の反応式
[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]

参加物

7

反応物 5

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

生成物 1

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

試薬・触媒・溶媒 1

HCID 702Ethanol溶媒

実験手順

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).

後処理

  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)

出典と根拠

ORDレコード
ord-b5a690cc633e422e89a7f8f838359086
出典データセット
uspto-grants-2004_01
特許番号
US06677337B2

反応ノート

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