Hydrazine → (1S,4S)-2-(2-chloro-5-fluoro-6-hydrazino-4-pyrimidinyl)-5-methyl-2,5-diazabicyclo[2.2.1]heptane

HRID 1366403Notes

Reaction equation

HRID 1366403 reaction equation
[Cl:1][C:2]1[N:7]=[C:6](Cl)[C:5]([F:9])=[C:4](Cl)[N:3]=1.Br.Br.[CH3:13][N:14]1[CH2:19][C@@H:18]2[CH2:20][C@H:15]1[CH2:16][NH:17]2.CCN(C(C)C)C(C)C.[NH2:30][NH2:31]>CS(C)=O>[Cl:1][C:2]1[N:7]=[C:6]([N:17]2[CH2:16][C@@H:15]3[CH2:20][C@H:18]2[CH2:19][N:14]3[CH3:13])[C:5]([F:9])=[C:4]([NH:30][NH2:31])[N:3]=1

Participants

6

Reactant 4

HCID 9321HydrazineHCID 81531DiisopropylethylamineHCID 133889932,4,6-Trichloro-5-fluoropyrimidineHCID 15629279(1S)-2-methyl-2,5-diazobicyclo[2.2.1]heptane dihydrobromide

Product 1

HCID 86636925(1S,4S)-2-(2-chloro-5-fluoro-6-hydrazino-4-pyrimidinyl)-5-methyl-2,5-diazabicyclo[2.2.1]heptane

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Procedure

2,4,6-Trichloro-5-fluoropyrimidine (2.01 g, 10 mmol) was dissolved in 30 mL of DMSO and stirred at room temperature. Commercially-available (1S,4S)-2-methyl-2,5-diazabicyclo[2.2.1]heptane, dihydrobromide (2.74 g, 10 mmol) was added, followed by DIPEA (5.51 mL, 32 mmol). The resulting reaction mixture was stirred for 2.5 h, and then hydrazine was added (3.0 mL) and the contents were stirred at room temperature overnight. The reaction mixture was then purified by RP-HPLC to provide the assumed (1S,4S)-2-(2-chloro-5-fluoro-6-hydrazino-4-pyrimidinyl)-5-methyl-2,5-diazabicyclo[2.2.1]heptane (first eluent), as well as the assumed 4-chloro-5-fluoro-6-[(1S,4S)-5-methyl-2,5-diazabicyclo[2.2.1]hept-2-yl]-2(1H)-pyrimidinone hydrazone (second eluent).

Workup

  1. customThe resulting reaction mixture
  2. stirringwas stirred for 2.5 h
  3. stirringthe contents were stirred at room temperature overnight
  4. customThe reaction mixture was then purified by RP-HPLC

Sources & evidence

ORD record
ord-26ddea0079694ef6998483af9c93f35c
Source dataset
uspto-grants-2011_02
Patent number
US07893056B2

Reaction notes

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