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 451038Notes

Reaction equation

HRID 451038 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-ebb399b157e9490abb7f12606e70e665
Source dataset
uspto-grants-2013_07
Patent number
US08486952B2

Reaction notes

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