Pyridine → 2-[2-(tert-Butyl-dimethyl-silanyloxy)-ethylamino]-6-chloro-nicotinonitrile

HRID 1483752Notes

Reaction equation

[C:1]([Si:5]([CH3:21])([CH3:20])[O:6][CH2:7][CH2:8][NH:9][C:10]1[N:18]=[C:17]([Cl:19])[CH:16]=[CH:15][C:11]=1[C:12]([NH2:14])=O)([CH3:4])([CH3:3])[CH3:2].N1C=CC=CC=1.O=P(Cl)(Cl)Cl.[OH-].[Na+]>C(#N)C.CCOC(C)=O>[C:1]([Si:5]([CH3:21])([CH3:20])[O:6][CH2:7][CH2:8][NH:9][C:10]1[N:18]=[C:17]([Cl:19])[CH:16]=[CH:15][C:11]=1[C:12]#[N:14])([CH3:4])([CH3:3])[CH3:2]

Participants

Conditions

Temperature: 60 °C

Procedure

To a solution of 2-[2-(tert-butyl-dimethyl-silanyloxy)-ethylamino]-6-chloro-nicotinamide (3, 300 mg, 0.96 mmol) in acetonitrile (anhydrous, 50 mL) were added pyridine (0.62 mL, 7.65 mmol) and POCl3 (0.35 mL, 382 mmol). The reaction was heated at 60° C. for 1 hour. After cooling to room temperature, NaOH solution (10% aq.) was slowly added till pH 9. EtOAc (200 mL) was added and the layers separated. The aqueous layer was extracted with EtOAc (2×200 mL). The combined organic layer was dried over MgSO4, filtered, and concentrated in vacuo. Purification was accomplished by silica gel chromatography, eluting with 1%-20% EtOAc/hexanes gradient, to afford 220 mg (78% yield) of the titled product.

Workup

temperatureAfter cooling to room temperature
customthe layers separated
extractionThe aqueous layer was extracted with EtOAc (2×200 mL)
dry with materialThe combined organic layer was dried over MgSO4
filtrationfiltered
concentrationconcentrated in vacuo
customPurification
washeluting with 1%-20% EtOAc/hexanes gradient

Sources & evidence

ORD record: ord-3e37a75ea94846bca02f184eedd8d972
Source dataset: uspto-grants-2016_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09416146B2

Reaction notes

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