N-methyl-2-pyrrolidone → HCID 66985318, compound

HRID 2191543Notes

Reaction equation

HRID 2191543 reaction equation
Cl[C:2]1[C:3]2[CH:10]([CH3:11])[O:9][CH2:8][C:4]=2[N:5]=[CH:6][N:7]=1.[C:12]([O:16][C:17]([N:19]1[CH2:24][CH2:23][NH:22][C@@H:21]([CH3:25])[CH2:20]1)=[O:18])([CH3:15])([CH3:14])[CH3:13].CN1C(=O)CCC1>O.CCOC(C)=O>[CH3:25][C@@H:21]1[N:22]([C:2]2[C:3]3[CH:10]([CH3:11])[O:9][CH2:8][C:4]=3[N:5]=[CH:6][N:7]=2)[CH2:23][CH2:24][N:19]([C:17]([O:16][C:12]([CH3:13])([CH3:15])[CH3:14])=[O:18])[CH2:20]1

Participants

6

Reactant 3

HCID 13387N-methyl-2-pyrrolidoneHCID 7023035(S)-1-Boc-3-methylpiperazineHCID 584973354-Chloro-5-methyl-5,7-dihydrofuro[3,4-d]pyrimidine

Product 1

HCID 66985318HCID 66985318, compoundYield 89%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
90 °C

Procedure

A mixture of 4-chloro-5-methyl-5,7-dihydrofuro[3,4-d]pyrimidine (0.340 g, 1.99 mmol), (S)-tert-butyl-3-methylpiperazine-1-carboxylate (0.439, 2.19 mmol), TEA (0.56 mL, 4.0 mmol) and NMP (3 mL) was heat to 90° C. for 4 hours. The reaction was cooled to room temperature and diluted with H2O and EtOAc. The organic layer was separated and the aqueous layer extracted with EtOAc (3×20 mL). The combined organics were dried with MgSO4 and concentrated. The residue was purified by column chromatography (EtOAc) to give (3S)-tert-butyl 3-methyl-4-(5-methyl-5,7-dihydrofuro[3,4-d]pyrimidin-4-yl)piperazine-1-carboxylate (0.590 g, 89%) as an off white solid. LCMS (APCI+) m/z 235 [M-C5H9O2+H+]; Rt=2.71 min. This material was dissolved in DCM (5 mL) to which was added excess 4 N HCl in dioxane (2 mL) and the reaction allowed to stir at room temperature overnight. The reaction was concentrated to give 5-methyl-4-((S)-2-methylpiperazin-1-yl)-5,7-dihydrofuro[3,4-d]pyrimidine dihydrochloride (0.540 g, 93%) was an off white solid. 1H NMR (CD3OD, 400 MHz) δ 8.82 (s, 1H), 5.83-5.79 (m, 1H), 5.18-5.05 (m, 1H), 4.48-4.36 (m, 1H), 3.87-3.73 (m, 1H), 3.58-3.52 (m, 1H), 3.48-3.43 (m, 3H), 1.51-1.46 (m, 5H). LCMS (APCI+) m/z 235 [M+H+]; Rt=1.13 min.

Workup

  1. temperatureThe reaction was cooled to room temperature
  2. customThe organic layer was separated
  3. extractionthe aqueous layer extracted with EtOAc (3×20 mL)
  4. dry with materialThe combined organics were dried with MgSO4
  5. concentrationconcentrated
  6. customThe residue was purified by column chromatography (EtOAc)

Sources & evidence

ORD record
ord-dd8266b50412402f986beb3138d5e655
Source dataset
uspto-grants-2012_12
Patent number
US08329701B2

Reaction notes

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