Hydrazine hydrate (1:1) → 5-Fluoro-4-hydrazino-2-methyl-6-[3-methyl-3-(1-pyrrolidinyl)-1-azetidinyl]pyrimidine

HRID 1366588Notes

Reaction equation

HRID 1366588 reaction equation
Cl[C:2]1[C:7]([F:8])=[C:6](Cl)[N:5]=[C:4]([CH3:10])[N:3]=1.Cl.Cl.[CH3:13][C:14]1([N:18]2[CH2:22][CH2:21][CH2:20][CH2:19]2)[CH2:17][NH:16][CH2:15]1.CCN(C(C)C)C(C)C.O.[NH2:33][NH2:34]>CS(C)=O>[F:8][C:7]1[C:2]([NH:33][NH2:34])=[N:3][C:4]([CH3:10])=[N:5][C:6]=1[N:16]1[CH2:17][C:14]([CH3:13])([N:18]2[CH2:22][CH2:21][CH2:20][CH2:19]2)[CH2:15]1

Participants

6

Reactant 4

HCID 24654Hydrazine hydrate (1:1)HCID 81531DiisopropylethylamineHCID 137310334,6-Dichloro-5-fluoro-2-methylpyrimidineHCID 669364881-(3-Methylazetidin-3-yl)pyrrolidine;dihydrochloride

Product 1

HCID 669366335-Fluoro-4-hydrazino-2-methyl-6-[3-methyl-3-(1-pyrrolidinyl)-1-azetidinyl]pyrimidineYield 71%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Procedure

To a mixture of 4,6-dichloro-5-fluoro-2-methylpyrimidine (90 mg, 0.50 mmol), 1-(3-methyl-3-azetidinyl)pyrrolidine dihydrochloride (Example 176) (131 mg, assumed 86% pure, 0.53 mmol) in 5 mL of DMSO was added DIPEA (0.345 mL, 1.98 mmol). The resulting reaction mixture was stirred at rt overnight, and then hydrazine monohydrate was added (0.5 mL) and the contents were heated to 80° C. for 4 h. The reaction mixture was then cooled to room temperature and purified by RP-HPLC to provide 5-fluoro-4-hydrazino-2-methyl-6-[3-methyl-3-(1-pyrrolidinyl)-1-azetidinyl]pyrimidine (100 mg, 71%). LCMS: (M+H)+: 281.0.

Workup

  1. customThe resulting reaction mixture
  2. temperaturethe contents were heated to 80° C. for 4 h
  3. temperatureThe reaction mixture was then cooled to room temperature
  4. custompurified by RP-HPLC

Sources & evidence

ORD record
ord-8953806d241142a2a0277ea2bc9612fa
Source dataset
uspto-grants-2011_02
Patent number
US07893056B2

Reaction notes

Loading…