2-Chloro-5-fluoropyrimidine → 5-fluoro-2-[(3R)-3-methylpiperazin-1-yl]pyrimidine

HRID 888183Notes

Reaction equation

HRID 888183 reaction equation
Cl[C:2]1[N:7]=[CH:6][C:5]([F:8])=[CH:4][N:3]=1.[CH3:9][C@@H:10]1[CH2:15][NH:14][CH2:13][CH2:12][NH:11]1>CC(O)C.CCN(C(C)C)C(C)C>[F:8][C:5]1[CH:4]=[N:3][C:2]([N:14]2[CH2:13][CH2:12][NH:11][C@H:10]([CH3:9])[CH2:15]2)=[N:7][CH:6]=1

Participants

5

Reactant 2

HCID 5834662-Chloro-5-fluoropyrimidineHCID 73304342-Methylpiperazine, (R)-

Product 1

HCID 584880425-fluoro-2-[(3R)-3-methylpiperazin-1-yl]pyrimidineYield 117.8%

Reagents, catalysts & solvents 2

HCID 3776IsopropanolSolventHCID 81531DiisopropylethylamineSolvent

Procedure

A solution of 2-chloro-5-fluoropyrimidine (239 mg, 1.80 mmol) and (R)-2-methylpiperazine (271 mg, 2.71 mmol) in iPrOH (1 mL) and DIEA (617 μL) was heated in MW at 130° C. for 30 min. Solvent was removed under reduced pressure and the crude (600 mg) was purified by chromatography on silica using DCM/methanol (9/1) as eluent to afford The title compound as a white solid (416 mg, quantitative). TLC-DCM/MeOH (8/2); Rf: 0.3. 1H NMR (DMSO-d6) δ 8.14 (s, 2H), 4.48 (d, J=13.2 Hz, 2H), 4.33 (brs, 1H), 2.98-3.13 (m, 2H), 2.83 (m, 2H), 2.67 (t, J=12.7 Hz, 1H), 1.20 (m, 3H).

Workup

  1. customSolvent was removed under reduced pressure
  2. customthe crude (600 mg) was purified by chromatography on silica

Sources & evidence

ORD record
ord-e638542a87af4be68413298932951fce
Source dataset
uspto-grants-2012_08
Patent number
US08247437B2

Reaction notes

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