Cesium carbonate → Benzyl 4-{[(5-fluoro-pyrimidin-2-yl)amino]methyl}piperidine-1-carboxylate

HRID 1827229Notes

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]([F:26])=[CH:22][N:21]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>CN(C=O)C.C(OCC)(=O)C>[F: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: 100 °C

Procedure

A stirred mixture of benzyl 4-(aminomethyl)piperidine-1-carboxylate (EXAMPLE 13, STEP 1) (10.0 g, 0.040 mol), 2-chloro-5-fluoropyrimidine (5.3 g, 0.040 mol) and cesium carbonate (26.2 g, 0.081 mol) in DMF (100 mL) was heated at 100° C. for 2 h. The reaction mixture was cooled to rt, diluted with ethyl acetate (400 mL), washed with aqueous saturated NaHCO3 (100 mL), water (5×100 mL), and brine (50 mL), dried over anhydrous Na2SO4, filtered and concentrated. The residue was chromatographed on silica gel 60 (0.5 kg), eluting with 50–100% ethyl acetate in hexane to give the title compound. M.S. (M+1): 345.

Workup

temperatureThe reaction mixture was cooled to rt
washwashed with aqueous saturated NaHCO3 (100 mL), water (5×100 mL), and brine (50 mL)
dry with materialdried over anhydrous Na2SO4
filtrationfiltered
concentrationconcentrated
customThe residue was chromatographed on silica gel 60 (0.5 kg)
washeluting with 50–100% ethyl acetate in hexane

Sources & evidence

ORD record: ord-ca227a6b359e443691ededefc2b71f92
Source dataset: uspto-grants-2006_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07053089B2

Reaction notes

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