Dimethylformamide → 2-(5-amino-pyridin-3-yl)-6-chloro-1-methyl-1H-indole-3-carbonitrile

HRID 593661Notes

Reaction equation

ClS([N:5]=[C:6]=O)(=O)=O.CC(OC([N:15](C(OC(C)(C)C)=O)[C:16]1[CH:17]=[N:18][CH:19]=[C:20]([C:22]2[N:23]([CH3:32])[C:24]3[C:29]([CH:30]=2)=[CH:28][CH:27]=[C:26]([Cl:31])[CH:25]=3)[CH:21]=1)=O)(C)C.CN(C=O)C>C(#N)C>[NH2:15][C:16]1[CH:21]=[C:20]([C:22]2[N:23]([CH3:32])[C:24]3[C:29]([C:30]=2[C:6]#[N:5])=[CH:28][CH:27]=[C:26]([Cl:31])[CH:25]=3)[CH:19]=[N:18][CH:17]=1

Participants

Conditions

Temperature: 65 °C

Procedure

Chlorosulfonyl isocyanate (1.63 g, 11.5 mmol) is added to a solution of 3-[bis[[(1,1-dimethylethyl)oxy]carbonyl]amino]-5-(6-chloro-1-methyl-1H-indol-2-yl)-pyridine (0.91 g, 1.99 mmol) in acetonitrile (200 mL) and the reaction mixture is stirred for 10 min. DMF (3 mL) is added and the reaction mixture is stirred for 3 h. 20 g silica gel is added to the mixture and the solvent is removed in vacuo. The resulting solid is heated to 65° C. under high vacuum for 2 h. The mixture is cooled to room temperature and then purified by silica gel flash chromatography (dichloromethane-methanol-triethylamine, 83:8:9) to afford 2-(5-amino-pyridin-3-yl)-6-chloro-1-methyl-1H-indole-3-carbonitrile. 1H NMR (400 MHz, DMSO-d6) δ ppm 3.76 (s, 3H), 5.72 (s, 2H), 7.15 (t, J=2.3 Hz, 1H), 7.35 (dd, J=8.5, 1.9 Hz, 1H), 7.69 (d, J=8.3 Hz, 1H), 7.92 (d, J=1.8 Hz, 1H), 7.97 (d, J=1.8 Hz, 1H), 8.12 (d, J=2.5 Hz, 1H). MS (ESI) m/z 283.0 (M+H)+.

Workup

stirringthe reaction mixture is stirred for 3 h
addition20 g silica gel is added to the mixture
customthe solvent is removed in vacuo
temperatureThe mixture is cooled to room temperature
custompurified by silica gel flash chromatography (dichloromethane-methanol-triethylamine, 83:8:9)

Sources & evidence

ORD record: ord-e4bfbcc214fc469d86bb70cd6d84dbdd
Source dataset: uspto-grants-2016_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09242963B2

Reaction notes

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