tert-Butyl 1-[4-(aminocarbonyl)-6-chloropyridin-2-yl]piperidin-4-ylcarbamate → tert-Butyl {1-[4-(aminocarbonyl)-6-cyanopyridin-2-yl]piperidin-4-yl}carbamate

HRID 2233838Notes

Reaction equation

[NH2:1][C:2]([C:4]1[CH:9]=[C:8](Cl)[N:7]=[C:6]([N:11]2[CH2:16][CH2:15][CH:14]([NH:17][C:18](=[O:24])[O:19][C:20]([CH3:23])([CH3:22])[CH3:21])[CH2:13][CH2:12]2)[CH:5]=1)=[O:3].[Cu](C#N)[C:26]#[N:27]>O1CCOCC1.CCOC(C)=O.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.[Fe+2]>[NH2:1][C:2]([C:4]1[CH:9]=[C:8]([C:26]#[N:27])[N:7]=[C:6]([N:11]2[CH2:16][CH2:15][CH:14]([NH:17][C:18](=[O:24])[O:19][C:20]([CH3:23])([CH3:22])[CH3:21])[CH2:13][CH2:12]2)[CH:5]=1)=[O:3]

Participants

Conditions

Temperature: 100 °C

Procedure

tert-Butyl {1-[4-(aminocarbonyl)-6-chloropyridin-2-yl]piperidin-4-yl}carbamate (Intermediate 16) (100 mg, 0.282 mmol), copper cyanide (101 mg, 1.13 mmol), Pd(dba) (103 mg, 0.11 mmol) and Dppf (250 mg, 0.45 mmol) were placed in anhydrous dioxane (5 ml) under argon. The mixture was heated at 100° C. for 5 h, then diluted with EtOAc (20 ml) and filtered through celite. The mixture was washed with sodium bicarbonate (2×20 ml), brine (20 ml), dried over sodium sulphate and concentrated in vacuo. The brown residue was purified by flash chromatography eluting with DCM and MeOH mixtures to give the title compound as a brown solid (61 mg).

Workup

filtrationfiltered through celite
washThe mixture was washed with sodium bicarbonate (2×20 ml), brine (20 ml)
dry with materialdried over sodium sulphate
concentrationconcentrated in vacuo
customThe brown residue was purified by flash chromatography
washeluting with DCM and MeOH mixtures

Sources & evidence

ORD record: ord-61e577fc18c04c1c81f1615972b4378d
Source dataset: uspto-grants-2010_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07709503B2

Reaction notes

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