Cesium carbonate → (S)-tert-butyl 1-(5-aminopyrimidin-4-yl)piperidin-3-ylcarbamate

HRID 716176Notes

Reaction equation

[NH:1]1[CH2:6][CH2:5][CH2:4][C@H:3]([NH:7][C:8](=[O:14])[O:9][C:10]([CH3:13])([CH3:12])[CH3:11])[CH2:2]1.[NH2:15][C:16]1[C:17](Cl)=[N:18][CH:19]=[N:20][CH:21]=1.C([O-])([O-])=O.[Cs+].[Cs+]>CN(C=O)C.CCOC(C)=O>[NH2:15][C:16]1[C:17]([N:1]2[CH2:6][CH2:5][CH2:4][C@H:3]([NH:7][C:8](=[O:14])[O:9][C:10]([CH3:11])([CH3:13])[CH3:12])[CH2:2]2)=[N:18][CH:19]=[N:20][CH:21]=1

Participants

Conditions

Temperature: 150 °C

Procedure

tert-butyl ((3S)-1-(5-amino-4-pyrimidinyl)-3-piperidinyl) carbamate. A mixture of (S)-tert-butyl piperidin-3-ylcarbamate (486 mg, 2.42 mmol), 5-amino -4-chloropyrimidine (262 mg, 2.02 mmol, Magical Scientific, Atchison, Kans.) and Cs2CO3 (988 mg, 3.03 mmol) in 2 mL of DMF was heated in a microwave at 150° C. for 45 min. The mixture was diluted with 50 mL of EtOAc and filtered through a pad of Celite. The filtrate was washed with 5 mL saturated NH4Cl (aq.) followed by 5 mL of brine. The organic solution was concentrated and purified by silica gel chromatography (60-100% EtOAc in hexanes) to give tert-butyl ((3S)-1-(5-amino-4-pyrimidinyl)-3-piperidinyl)carbamate (233 mg, 39% yield, 90% purity). This material used without further purification. MS (ESI, pos. ion) m/z: 294.2 (M+1).

Workup

filtrationfiltered through a pad of Celite
washThe filtrate was washed with 5 mL saturated NH4Cl (aq.)
concentrationThe organic solution was concentrated
custompurified by silica gel chromatography (60-100% EtOAc in hexanes)

Sources & evidence

ORD record: ord-9715b95f835c416fbfa171459e94b386
Source dataset: uspto-grants-2015_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09187486B2

Reaction notes

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