Diisopropylethylamine → (S)-1'-(5-ethylpyrimidin-2-yl)-3-(2-fluoro-4-(methylsulfonyl)phenylamino)-1,4'-bipiperidin-2-one

HRID 407918Notes

Reaction equation

Cl.[F:2][C:3]1[CH:8]=[C:7]([S:9]([CH3:12])(=[O:11])=[O:10])[CH:6]=[CH:5][C:4]=1[NH:13][C@H:14]1[CH2:19][CH2:18][CH2:17][N:16]([CH:20]2[CH2:25][CH2:24][NH:23][CH2:22][CH2:21]2)[C:15]1=[O:26].Cl[C:28]1[N:33]=[CH:32][C:31]([CH2:34][CH3:35])=[CH:30][N:29]=1.CCN(C(C)C)C(C)C>CN(C=O)C>[CH2:34]([C:31]1[CH:30]=[N:29][C:28]([N:23]2[CH2:22][CH2:21][CH:20]([N:16]3[CH2:17][CH2:18][CH2:19][C@H:14]([NH:13][C:4]4[CH:5]=[CH:6][C:7]([S:9]([CH3:12])(=[O:11])=[O:10])=[CH:8][C:3]=4[F:2])[C:15]3=[O:26])[CH2:25][CH2:24]2)=[N:33][CH:32]=1)[CH3:35]

Participants

Conditions

Temperature: 100 °C

Procedure

(S)-3-(2-fluoro-4-(methylsulfonyl)phenylamino)-1,4′-bipiperidin-2-one hydrochloride (prepared according to the method of Example 45) (0.35 g, 0.862 mmol), 2-chloro-5-ethylpyrimidine (0.123 g, 0.862 mmol) and DIEA (0.334 g, 2.59 mmol) were dissolved in DMF (5 mL) and The reaction was stirred at 100° C. overnight. The reaction was cooled to ambient temperature and concentrated. The residue was purified over silica gel (50-100% EtOAc in hexanes) to afford (S)-1′-(5-ethylpyrimidin-2-yl)-3-(2-fluoro-4-(methylsulfonyl)phenylamino)-1,4′-bipiperidin-2-one (0.142 g, 0.299 mmol, 34.6% yield) as a yellow solid. Mass spectrum (apci) m/z=476.2 (M+H).

Workup

temperatureThe reaction was cooled to ambient temperature
concentrationconcentrated
customThe residue was purified over silica gel (50-100% EtOAc in hexanes)

Sources & evidence

ORD record: ord-f9597875d88843ad88bc4a377b4c7abe
Source dataset: uspto-grants-2014_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08754226B2

Reaction notes

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