4-Methylpiperidin-4-ol → 1-(2-chloro-7-(4-fluorophenyl)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)-4-methylpiperidin-4-ol

HRID 2370119Notes

Reaction equation

HRID 2370119 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][C:20]1([OH:26])[CH2:25][CH2:24][NH:23][CH2:22][CH2:21]1>CO>[Cl:1][C:2]1[N:3]=[C:4]([N:23]2[CH2:24][CH2:25][C:20]([CH3:19])([OH:26])[CH2:21][CH2:22]2)[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 156491744-Methylpiperidin-4-olHCID 580754242,4-Dichloro-7-(4-fluorophenyl)-6,7-dihydro-5H-cyclopenta[D]pyrimidine

Product 1

HCID 580753921-(2-chloro-7-(4-fluorophenyl)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)-4-methylpiperidin-4-olYield 73.2%

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) (400 mg, 1.413 mmol) in MeOH (14.100 mL) was added 4-methylpiperidin-4-ol (163 mg, 1.413 mmol). The resulting mixture was stirred at RT overnight. The reaction mixture was then concentrated in vacuo. Purification by flash chromatography (Silica, EtOAc/Hexanes) gave 1-(2-chloro-7-(4-fluorophenyl)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)-4-methylpiperidin-4-ol (374 mg, 1.034 mmol, 73.2% yield). LC-MS (M+H)+=362.0. 1H NMR (500 MHz, MeOD) δ ppm 7.12-7.21 (2 H, m), 7.04 (2 H, t, J=8.85 Hz), 4.11-4.30 (3 H, m), 3.48-3.63 (2 H, m), 3.14-3.23 (1 H, m), 3.00-3.12 (1 H, m), 2.54-2.66 (1 H, m), 1.94-2.09 (1 H, m), 1.68 (4 H, t, J=4.12 Hz), 1.28 (3 H, s).

Workup

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

Sources & evidence

ORD record
ord-0729d01cf6ed46b3b997778cfcf324a3
Source dataset
uspto-grants-2014_04
Patent number
US08710061B2

Reaction notes

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