Dimethylacetamide → 6-Amino-4-chloro-3-pyridinecarbonitrile

HRID 1777862Notes

Reaction equation

Br[C:2]1[C:3]([Cl:9])=[CH:4][C:5]([NH2:8])=[N:6][CH:7]=1.C[C:11]([N:13](C)C)=O>CCOC(C)=O.[C-]#N.[Zn+2].[C-]#N.[Zn].C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].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]>[NH2:8][C:5]1[CH:4]=[C:3]([Cl:9])[C:2]([C:11]#[N:13])=[CH:7][N:6]=1

Participants

Conditions

Temperature: 70 °C

Procedure

5-bromo-4-chloropyridin-2-amine (500 mg, 2.41 mmol), zinc cyanide (297 mg, 2.53 mmol), zinc (31.5 mg, 0.482 mmol), Pd2(dba)3 (221 mg, 0.241 mmol), dppf (267 mg, 0.482 mmol) and DMA (20 ml) were charged into a flask under argon. The reaction mixture was stirred at 70° C. for 16 h. The reaction mixture was diluted in EtOAc and washed with sat. NaHCO3 (2×) and brine. The combined organic layers were dried over Na2SO4, filtered and concentrated under reduced pressure. The crude material was purified by normal phase chromatography (24 g silica gel cartridge, heptanes/EtOAc 100:0 to 58:42) to give the title compound as a beige solid. (UPLC-MS 1) tR 0.57 min; ESI-MS 154.0 [M+H]+.

Workup

washwashed with sat. NaHCO3 (2×) and brine
dry with materialThe combined organic layers were dried over Na2SO4
filtrationfiltered
concentrationconcentrated under reduced pressure
customThe crude material was purified by normal phase chromatography (24 g silica gel cartridge, heptanes/EtOAc 100:0 to 58:42)

Sources & evidence

ORD record: ord-94680d31a7d143e68caf4884a27b3b13
Source dataset: uspto-grants-2016_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09266883B2

Reaction notes

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