2,6-Dimethylmorpholine, cis- → (2S,6R)-4-(2-chloro-7-(4-fluorophenyl)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)-2,6-dimethylmorpholine

HRID 475752Notes

Reaction equation

HRID 475752 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@H:20]1[O:25][C@@H:24]([CH3:26])[CH2:23][NH:22][CH2:21]1>CO>[Cl:1][C:2]1[N:3]=[C:4]([N:22]2[CH2:21][C@@H:20]([CH3:19])[O:25][C@@H:24]([CH3:26])[CH2:23]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 6415002,6-Dimethylmorpholine, cis-2×HCID 580754242,4-Dichloro-7-(4-fluorophenyl)-6,7-dihydro-5H-cyclopenta[D]pyrimidine

Product 1

HCID 58075482(2S,6R)-4-(2-chloro-7-(4-fluorophenyl)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)-2,6-dimethylmorpholineYield 87.3%

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 cis-2,6-Dimethylmorpholine (105 μL, 0.848 mmol). The resulting mixture was stirred at RT overnight. An additional 2 equ. of cis-2,6-Dimethylmorpholine was then added and the mixture was again stirred overnight at RT. The reaction mixture was then concentrated in vacuo. The resulting oil was purified by flash chromatography (Silica, EtOAc/Hexanes) to give (2S,6R)-4-(2-chloro-7-(4-fluorophenyl)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)-2,6-dimethylmorpholine (223 mg, 0.616 mmol, 87% yield). LC-MS (M+H)+=332.1. 1H NMR (500 MHz, MeOD) δ ppm 7.11-7.24 (2H, m), 6.99-7.09 (2H, m), 4.39-4.51 (2H, m), 4.20 (1H, s), 3.70 (2H, td, J=4.12, 2.44 Hz), 3.14-3.25 (1H, m), 3.03-3.13 (1H, m), 2.69-2.80 (2H, m), 2.54-2.68 (1H, m), 1.95-2.13 (1H, m), 1.23 (6H, d, J=6.10 Hz).

Workup

  1. waitthe mixture was again stirred overnight at RT
  2. concentrationThe reaction mixture was then concentrated in vacuo
  3. customThe resulting oil was purified by flash chromatography (Silica, EtOAc/Hexanes)

Sources & evidence

ORD record
ord-f6ec10bc23ed44a8a8591596063f0b1b
Source dataset
uspto-grants-2014_01
Patent number
US08637525B2

Reaction notes

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