Potassium Carbonate → HCID 86688095, compound

HRID 407934Notes

Reaction equation

Cl[C:2]1[N:3]=[CH:4][C:5]([N:8]2[CH2:13][CH2:12][CH:11]([N:14]3[CH2:19][CH2:18][CH2:17][C@H:16]([NH:20][C:21]4[CH:26]=[C:25]([F:27])[C:24]([S:28]([CH3:31])(=[O:30])=[O:29])=[CH:23][C:22]=4[F:32])[C:15]3=[O:33])[CH2:10][CH2:9]2)=[N:6][CH:7]=1.C([O-])([O-])=O.[K+].[K+].[CH2:40]([Zn]CC)[CH3:41]>C1COCC1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[F:32][C:22]1[CH:23]=[C:24]([S:28]([CH3:31])(=[O:30])=[O:29])[C:25]([F:27])=[CH:26][C:21]=1[NH:20][C@H:16]1[CH2:17][CH2:18][CH2:19][N:14]([CH:11]2[CH2:12][CH2:13][N:8]([C:5]3[CH:4]=[N:3][C:2]([CH2:40][CH3:41])=[CH:7][N:6]=3)[CH2:9][CH2:10]2)[C:15]1=[O:33]

Participants

Conditions

Temperature: 60 °C

Procedure

(S)-1′-(5-chloropyrazin-2-yl)-3-(2,5-difluoro-4-(methylsulfonyl)phenylamino)-1,4′-bipiperidin-2-one (prepared according to the procedure of Example 45) (50 mg, 0.100 mmol) was dissolved in THF (2 mL) and K2CO3 (41.5 mg, 0.300 mmol) and PdCl2(dppf)*CH2Cl2 (8.17 mg, 0.0100 mmol) were added and purged with nitrogen. 1M diethylzinc (110 μL, 0.110 mmol) was added and the reaction was heated to 60° C. for 3 hours. The reaction was cooled to ambient temperature, concentrated in vacuo and purified over silica gel (70 to 90% EtOAc in hexanes) to afford (S)-3-(2,5-difluoro-4-(methylsulfonyl)phenylamino)-1′-(5-ethylpyrazin-2-yl)-1,4′-bipiperidin-2-one (26.8 mg, 0.0543 mmol, 54.3% yield) as a tan solid. Mass spectrum (apci) m/z=494.3 (M+H).

Workup

custompurged with nitrogen
temperatureThe reaction was cooled to ambient temperature
concentrationconcentrated in vacuo
custompurified over silica gel (70 to 90% EtOAc in hexanes)

Sources & evidence

ORD record: ord-db551f655f0749849b47f53c1b2df1f3
Source dataset: uspto-grants-2014_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08754226B2

Reaction notes

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