2-Methylsulfanyl-pyrimidine-4-carbonyl chloride → 4-{N'-[2-(4-fluoro-phenyl)-acetyl]-N'-methyl-N-(2-methylsulfanyl-pyrimidine-4-carbonyl)-hydrazino}-piperidine-1-carboxylic acid tert-butyl ester

HRID 1838865Notes

Reaction equation

HRID 1838865 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([NH:14][N:15]([C:17](=[O:26])[CH2:18][C:19]2[CH:24]=[CH:23][C:22]([F:25])=[CH:21][CH:20]=2)[CH3:16])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH3:27][S:28][C:29]1[N:34]=[C:33]([C:35](Cl)=[O:36])[CH:32]=[CH:31][N:30]=1>N1C=CC=CC=1.Cl>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([N:14]([C:35]([C:33]2[CH:32]=[CH:31][N:30]=[C:29]([S:28][CH3:27])[N:34]=2)=[O:36])[N:15]([C:17](=[O:26])[CH2:18][C:19]2[CH:20]=[CH:21][C:22]([F:25])=[CH:23][CH:24]=2)[CH3:16])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

5

Reactant 2

HCID 115429012-Methylsulfanyl-pyrimidine-4-carbonyl chlorideHCID 600611354-{N'-[2-(4-fluoro-phenyl)-acetyl]-N'-methyl-hydrazino}-piperidine-1-carboxylic acid tert-butyl ester

Product 1

HCID 115916664-{N'-[2-(4-fluoro-phenyl)-acetyl]-N'-methyl-N-(2-methylsulfanyl-pyrimidine-4-carbonyl)-hydrazino}-piperidine-1-carboxylic acid tert-butyl esterYield 20%

Reagents, catalysts & solvents 2

HCID 313Hydrochloric AcidSolventHCID 1049PyridineSolvent

Procedure

To a stirred solution of 4-{N′-[2-(4-fluoro-phenyl)-acetyl]-N′-methyl-hydrazino}-piperidine-1-carboxylic acid tert-butyl ester, 9, (3.7 g, 10.1 mmol) in pyridine (10 mL) is added 2-methylsulfanyl-pyrimidine-4-carbonyl chloride (2.9 g, 15.2 mmol). The reaction mixture is stirred at room temperature for 2 hours then diluted with 0.1 N HCl and extracted three times with CH2Cl2. The combined organic layers are dried (MgSO4), filtered and concentrated in vacuo. Purification over silica (EtOAc/hexanes 1:1) affords 1.058 g (20% yield) of the desired product. ESI/MS: 518.2 (M+H).

Workup

  1. extractionextracted three times with CH2Cl2
  2. dry with materialThe combined organic layers are dried (MgSO4)
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo
  5. customPurification over silica (EtOAc/hexanes 1:1)

Sources & evidence

ORD record
ord-481fea5d30f140ed92f5ae3009981702
Source dataset
uspto-grants-2004_01
Patent number
US06677337B2

Reaction notes

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