Methyl isonipecotate → Methyl 1-(2-(5-(5-bromopyrimidin-2-ylamino)-2-fluorophenoxy)ethyl)piperidine-4-carboxylate

HRID 2067908

Reaction equation

CS(O[CH2:6][CH2:7][O:8][C:9]1[CH:14]=[C:13]([NH:15][C:16]2[N:21]=[CH:20][C:19]([Br:22])=[CH:18][N:17]=2)[CH:12]=[CH:11][C:10]=1[F:23])(=O)=O.[NH:24]1[CH2:29][CH2:28][CH:27]([C:30]([O:32][CH3:33])=[O:31])[CH2:26][CH2:25]1>CN1C(=O)CCC1.O>[Br:22][C:19]1[CH:20]=[N:21][C:16]([NH:15][C:13]2[CH:12]=[CH:11][C:10]([F:23])=[C:9]([CH:14]=2)[O:8][CH2:7][CH2:6][N:24]2[CH2:29][CH2:28][CH:27]([C:30]([O:32][CH3:33])=[O:31])[CH2:26][CH2:25]2)=[N:17][CH:18]=1

Participants

Conditions

Temperature: 90 °C

Procedure

2-(5-(5-bromopyrimidin-2-ylamino)-2-fluorophenoxy)ethyl methanesulfonate 46b (0.24 mmol) and methyl piperidine-4-carboxylate (0.48 mmol) are dissolved in NMP (2 mL) and heated to 90° C. for 3 h. The reaction mixture is cooled to rt and diluted with water and extracted with EtOAc (2×30 mL). The organic layer is washed with water, brine, dried over sodium sulfate, and concentrated to dryness. The crude product is purified by short SiO2 chromatography using DCM:hexane=9:1 as eluant to yield methyl 1-(2-(5-(5-bromopyrimidin-2-ylamino)-2-fluorophenoxy)ethyl)piperidine-4-carboxylate 47 as light brown solid. MS (m/z) (M+1)+: 454.1.

Workup

temperatureThe reaction mixture is cooled to rt
extractionextracted with EtOAc (2×30 mL)
washThe organic layer is washed with water, brine
dry with materialdried over sodium sulfate
concentrationconcentrated to dryness
customThe crude product is purified by short SiO2 chromatography

Sources & evidence

ORD record: ord-5eacd9c8f44141448122ab8b1c12f878
Source dataset: uspto-grants-2012_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08293757B2

Linked notes

Loading…