Dimethyl Sulfoxide → (R)-tert-butyl 4-(5-methyl-7-oxo-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)piperazine-1-carboxylate

HRID 1675871Notes

Reaction equation

HRID 1675871 reaction equation
C(Cl)(=O)C(Cl)=O.CS(C)=O.[OH:11][CH:12]1[C:16]2[N:17]=[CH:18][N:19]=[C:20]([N:21]3[CH2:26][CH2:25][N:24]([C:27]([O:29][C:30]([CH3:33])([CH3:32])[CH3:31])=[O:28])[CH2:23][CH2:22]3)[C:15]=2[C@H:14]([CH3:34])[CH2:13]1.O>C(Cl)Cl.CCOC(C)=O>[CH3:34][C@H:14]1[C:15]2[C:20]([N:21]3[CH2:26][CH2:25][N:24]([C:27]([O:29][C:30]([CH3:33])([CH3:32])[CH3:31])=[O:28])[CH2:23][CH2:22]3)=[N:19][CH:18]=[N:17][C:16]=2[C:12](=[O:11])[CH2:13]1

Participants

7

Reactant 4

HCID 679Dimethyl SulfoxideHCID 962WaterHCID 65578Oxalyl chlorideHCID 59580348(R)-tert-butyl 4-(7-hydroxy-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)piperazine-1-carboxylate

Product 1

HCID 59580350(R)-tert-butyl 4-(5-methyl-7-oxo-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)piperazine-1-carboxylateYield 79.7%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolvent4×HCID 8857Ethyl AcetateSolvent2×

Procedure

To a −78° C. solution of oxalyl chloride (0.203 mL, 2.33 mmol) in 10 mL DCM was added dropwise by syringe a solution of DMSO (0.330 mL, 4.66 mmol) in 3 mL DCM. The reaction mixture was stirred 35 minutes, then a solution of (R)-tert-butyl 4-(7-hydroxy-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)piperazine-1-carboxylate (0.556 g, 1.66 mmol) in 5 mL DCM was added slowly by syringe. The reaction mixture was stirred another 1 hour at −78° C., after which neat TEA (1.09 mL, 7.81 mmol) was added. The reaction mixture was then allowed to warm to room temperature, stirred 30 minutes, and H2O was added. The mixture was extracted with 3×75 mL DCM, and the combined extracts were dried (Na2SO4), filtered, and concentrated in vacuo. The crude was purified on silica gel (Biotage 40M): the column was flushed with about 300 mL 4:1 DCM:EtOAc, then gradient to 1:4 DCM: EtOAc to give (R)-tert-butyl 4-(5-methyl-7-oxo-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)piperazine-1-carboxylate (0.440 g, 79.6% yield) as a brown foam. MS (APCI+) m/z 333 [M+H]−. 1H NMR (CDCl3, 400 MHz) δ 8.73 (s, 1H), 3.93-3.82 (m, 2H), 3.74-3.48 (m, 7H), 2.96 (dd, J=19.6, 7.3 Hz, 1H), 2.34 (dd, J=19.6, 1.5 Hz, 1H), 1.50 (s, 9H), 1.32 (d, J=6.8 Hz, 3H).

Workup

  1. stirringThe reaction mixture was stirred another 1 hour at −78° C.
  2. stirringstirred 30 minutes
  3. extractionThe mixture was extracted with 3×75 mL DCM
  4. dry with materialthe combined extracts were dried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe crude was purified on silica gel (Biotage 40M)
  8. customthe column was flushed with about 300 mL 4:1 DCM

Sources & evidence

ORD record
ord-8300c90e41d0459d8f3c4858df92b147
Source dataset
uspto-grants-2011_08
Patent number
US08003651B2

Reaction notes

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