Cesium carbonate → Benzyl 4-{[(5-methyl-2-pyrimidinyl)amino]methyl}-1-piperidinecarboxylate

HRID 1351594Notes

Reaction equation

[NH2:1][CH2:2][CH:3]1[CH2:8][CH2:7][N:6]([C:9]([O:11][CH2:12][C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)=[O:10])[CH2:5][CH2:4]1.Cl[C:20]1[N:25]=[CH:24][C:23]([CH3:26])=[CH:22][N:21]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>CN(C=O)C.C(OCC)(=O)C>[CH3:26][C:23]1[CH:22]=[N:21][C:20]([NH:1][CH2:2][CH:3]2[CH2:8][CH2:7][N:6]([C:9]([O:11][CH2:12][C:13]3[CH:14]=[CH:15][CH:16]=[CH:17][CH:18]=3)=[O:10])[CH2:5][CH2:4]2)=[N:25][CH:24]=1

Participants

Conditions

Temperature: 150 °C

Procedure

A stirred mixture of benzyl 4-(aminomethyl)-piperidine-1-carboxylate (EXAMPLE 13, STEP 1) (20.0 g, 0.081 mol), 2-chloro-5-methylpyrimidine (10.4 g, 0.081 mol) and cesium carbonate (52.5 g, 0.161 mol) in DMF (200 mL) was heated at 150° C. for 6 h. The reaction mixture was cooled to rt, diluted with ethyl acetate (700 mL), washed with aqueous saturated NaHCO3 (200 mL), water (5×200 mL), and brine (100 mL), dried over anhydrous sodium sulfate, filtered and concentrated. The residue was chromatographed on silica gel 60 (1 kg), eluting with 50–100% ethyl acetate in hexane to give the title compound. M.S. (M+1): 341.

Workup

temperatureThe reaction mixture was cooled to rt
washwashed with aqueous saturated NaHCO3 (200 mL), water (5×200 mL), and brine (100 mL)
dry with materialdried over anhydrous sodium sulfate
filtrationfiltered
concentrationconcentrated
customThe residue was chromatographed on silica gel 60 (1 kg)
washeluting with 50–100% ethyl acetate in hexane

Sources & evidence

ORD record: ord-2e5d5b310eaa4de38d599bd4d8231396
Source dataset: uspto-grants-2007_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07217716B2

Reaction notes

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