4-Fluorophenylacetyl 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 1838871Notes

Reaction equation

HRID 1838871 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([NH:14][N:15]([CH3:26])[C:16]([C:18]2[CH:23]=[CH:22][N:21]=[C:20]([S:24][CH3:25])[N:19]=2)=[O:17])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[F:27][C:28]1[CH:33]=[CH:32][C:31]([CH2:34][C:35](Cl)=[O:36])=[CH:30][CH:29]=1>N1C=CC=CC=1>[C:1]([O:5][C:6]([N:8]1[CH2:9][CH2:10][CH:11]([N:14]([C:35](=[O:36])[CH2:34][C:31]2[CH:32]=[CH:33][C:28]([F:27])=[CH:29][CH:30]=2)[N:15]([CH3:26])[C:16]([C:18]2[CH:23]=[CH:22][N:21]=[C:20]([S:24][CH3:25])[N:19]=2)=[O:17])[CH2:12][CH2:13]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

4

Reactant 2

HCID 37449884-Fluorophenylacetyl chlorideHCID 698477704-[N'-Methyl-N'-(2-methylsulfanyl-pyrimidine-4-carbonyl)-hydrazino]-piperidine-1-carboxylic acid tert-butyl ester

Product 1

HCID 600611404-{N-[2-(4-Fluoro-phenyl)-acetyl]-N'-methyl-N'-(2-methylsulfanyl-pyrimidine-4-carbonyl)-hydrazino}-piperidine-1-carboxylic acid tert-butyl ester

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Procedure

To a stirred 0° C. solution of 4-[N′-Methyl-N′-(2-methylsulfanyl-pyrimidine-4-carbonyl)-hydrazino]-piperidine-1-carboxylic acid tert-butyl ester, 16, (19.8 g, 51.7 mmol) in pyridine (25 mL) is added (4-fluorophenyl)acetyl chloride (10 g, 57.9 mmol). The reaction mixture is slowly warmed to room temperature and then stirred for 2 hours. The reaction mixture is then concentrated in vacuo. Purification over silica (100% EtOAc) affords 42 g of the desired product: 1H NMR (300 MHz, CDCl3) δ 8.80-8.70 (m, 1H), 7.40-7.32 (m, 1H), 7.29-7.18 (m, 2H), 7.07-6.94 (m, 2H), 4.24-4.10 (m, 3H), 3.82-3.59 (m, 2H), 3.33 (d, J=8.4 Hz, 3H), 2.88-2.67 (m, 2H), 2.60 (d, J=18.6 Hz, 3H), 1.96-1.92 (m, 2H), 1.70-1.65 (m, 2H), 1.48 (d, J=4.0 Hz, 9H); ESI/MS: 518.2 (M+H).

Workup

  1. concentrationThe reaction mixture is then concentrated in vacuo
  2. customPurification over silica (100% EtOAc)

Sources & evidence

ORD record
ord-bc08d42f652b4d4baf3c77fff609a07c
Source dataset
uspto-grants-2004_01
Patent number
US06677337B2

Reaction notes

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