N-methyl-2-pyrrolidone → 1,1-Dimethylethyl 4-(5,7-dihydro-5-methylfuro[3,4-d]pyrimidin-4-yl)-1-piperazinecarboxylate

HRID 2191538Notes

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

Participants

Conditions

Temperature: 90 °C

Procedure

A mixture of 4-chloro-5-methyl-5,7-dihydrofuro[3,4-d]pyrimidine (0.97 g, 5.7 mmol), N-Bocpiperazine (1.3 g, 6.8 mmol), TEA (1.6 mL, 11.4 mmol) and NMP (3 mL) was heated 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 tert-butyl 4-(5-methyl-5,7-dihydrofuro[3,4-d]pyrimidin-4-yl)piperazine-1-carboxylate (1.5 g, 83%) as an off white solid. 1H NMR (CDCl3, 400 MHz) δ 8.54 (s. 1H), 5.57-5.52 (m, 1H), 4.93 (d, J=2.0 Hz, 2H), 3.67-3.45 (m, 8H), 1.48 (s, 9H), 1.41 (d, J=6.0 Hz, 3H). LCMS (APCI+) m/z 321 [M+H+].

Workup

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

Sources & evidence

ORD record: ord-31f2add296ee44d5b2c091a733faf84e
Source dataset: uspto-grants-2012_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08329701B2

Reaction notes

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