2-Methylpyrrolidine → HCID 58075271, compound

HRID 451037Notes

Reaction equation

HRID 451037 reaction equation
[Cl:1][C:2]1[N:3]=[C:4](Cl)[C:5]2[CH2:10][CH2:9][CH:8]([C:11]3[CH:16]=[CH:15][C:14]([F:17])=[CH:13][CH:12]=3)[C:6]=2[N:7]=1.[CH3:19][CH:20]1[CH2:24][CH2:23][CH2:22][NH:21]1>CO>[Cl:1][C:2]1[N:3]=[C:4]([N:21]2[CH2:22][CH2:23][CH2:24][CH:20]2[CH3:19])[C:5]2[CH2:10][CH2:9][CH:8]([C:11]3[CH:16]=[CH:15][C:14]([F:17])=[CH:13][CH:12]=3)[C:6]=2[N:7]=1

Participants

4

Reactant 2

HCID 130032-MethylpyrrolidineHCID 580754242,4-Dichloro-7-(4-fluorophenyl)-6,7-dihydro-5H-cyclopenta[D]pyrimidine

Product 1

HCID 58075271HCID 58075271, compoundYield 33.9%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a solution of 2,4-dichloro-7-(4-fluorophenyl)-6,7-dihydro-5H-cyclopenta[d]pyrimidine (Preparation H) (200 mg, 0.706 mmol) in MeOH (7064 μL) was added 2-Methylpyrrolidine (82 μL, 0.848 mmol). The resulting mixture was stirred at RT for 2 days. The reaction mixture was then concentrated in vacuo. The resulting oil was purified by flash chromatography (Silica, EtOAc/Hexanes) to give two racemic pairs of diasteriomers 2-chloro-7-(4-fluorophenyl)-4-(2-methylpyrrolidin-1-yl)-6,7-dihydro-5H-cyclopenta[d]pyrimidine. (Hc1, Diastereomer 1, racemic, first to elute) (79.5 mg, 0.240 mmol, 33.9% yield). LC-MS (M+H)+=332.1; 1H NMR (500 MHz, MeOD) δ ppm 7.16 (2H, d, J=5.49 Hz), 7.04 (2H, s), 4.42-4.54 (1H, m), 4.09-4.22 (1H, m), 3.86-4.00 (1H, m), 3.71-3.82 (1H, m), 3.24-3.31 (1H, m), 3.10-3.22 (1H, m), 2.54-2.65 (1H, m), 2.05-2.16 (2H, m), 1.94-2.05 (2H, m), 1.69-1.80 (1H, m), 1.27 (3H, d, J=6.10 Hz). (Hc2, Diastereomer 2, racemic, second to elute) (89.5 mg, 0.270 mmol, 38% yield). LC-MS (M+H)+=332.1; 1H NMR (500 MHz, MeOD) δ ppm 7.14 (2H, d, J=5.49 Hz), 6.99-7.08 (2H, m), 4.42-4.54 (1H, m), 4.13-4.22 (1H, m), 3.86-4.00 (1H, m), 3.71-3.83 (1H, m), 3.25-3.32 (1H, m), 3.14-3.25 (1H, m), 2.52-2.67 (1H, m), 2.05-2.19 (2H, m), 1.94-2.05 (2H, m), 1.68-1.78 (1H, m), 1.19-1.32 (3H, m). The relative stereochemistry for Hc1 and Hc2 was not determined

Workup

  1. concentrationThe reaction mixture was then concentrated in vacuo
  2. customThe resulting oil was purified by flash chromatography (Silica, EtOAc/Hexanes)

Sources & evidence

ORD record
ord-f25611f3bb9d431c8d601ad389bef898
Source dataset
uspto-grants-2013_07
Patent number
US08486952B2

Reaction notes

Loading…