Ethyl Acetate → tert-Butyl 4-[2-(5-carbamoylpyrazin-2-ylamino)ethyl]piperidine-1-carboxylate

HRID 75109Notes

Reaction equation

Cl[C:2]1[N:3]=[CH:4][C:5]([C:8]([NH2:10])=[O:9])=[N:6][CH:7]=1.[NH2:11][CH2:12][CH2:13][CH:14]1[CH2:19][CH2:18][N:17]([C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[CH2:16][CH2:15]1.C(=O)([O-])[O-].[K+].[K+].C(OCC)(=O)C>CS(C)=O.O>[C:8]([C:5]1[N:6]=[CH:7][C:2]([NH:11][CH2:12][CH2:13][CH:14]2[CH2:15][CH2:16][N:17]([C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[CH2:18][CH2:19]2)=[N:3][CH:4]=1)(=[O:9])[NH2:10]

Participants

Conditions

Temperature: 100 °C

Procedure

A mixture of 1.12 g (7.15 mmol) of 5-chloropyrazine-2-carboxamide, 1.95 g (8.58 mmol) of tert-butyl 4-(2-aminoethyl)piperidine-1-carboxylate and 1.18 g (8.58 mmol) of potassium carbonate in 1.4 ml of dimethyl sulphoxide is heated during 5 hours at 100° C. under an argon atmosphere and with stirring. After cooling to ambient temperature, 25 ml of ethyl acetate and 25 ml of water are added. The organic phase is separated by settling and washed 3 times with 25 ml of water and then 25 ml of a saturated aqueous sodium chloride solution. It is dried over sodium sulphate and evaporated to dryness. The residue is purified by chromatography on silica gel, elution being carried out with a 97:3, then 95:5 and 93:7 mixture of dichloromethane and methanol, in order to obtain 1.99 g (5.69 mmol) of product in the form of a light-yellow paste.

Workup

temperatureAfter cooling to ambient temperature
customThe organic phase is separated by settling
washwashed 3 times with 25 ml of water
dry with materialIt is dried over sodium sulphate
customevaporated to dryness
customThe residue is purified by chromatography on silica gel, elution
addition95:5 and 93:7 mixture of dichloromethane and methanol

Sources & evidence

ORD record: ord-300b12ca0b2c44e29c34b070319d84be
Source dataset: uspto-grants-2014_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08835418B2

Reaction notes

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