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

HRID 1838870Notes

Reaction equation

HRID 1838870 reaction equation
[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]

Participants

7

Reactant 5

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

Product 1

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

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

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).

Workup

  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)

Sources & evidence

ORD record
ord-b5a690cc633e422e89a7f8f838359086
Source dataset
uspto-grants-2004_01
Patent number
US06677337B2

Reaction notes

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