Water → HCID 80522694, compound

HRID 920795Notes

Reaction equation

[H-].[Na+].[N:3]1[CH:8]=[CH:7][CH:6]=[C:5]([CH2:9][C:10]#[N:11])[CH:4]=1.Br[CH2:13][C:14]([O:19][CH3:20])([O:17][CH3:18])[CH2:15]Br.O>CN(C=O)C>[CH3:18][O:17][C:14]1([O:19][CH3:20])[CH2:15][C:9]([C:5]2[CH:4]=[N:3][CH:8]=[CH:7][CH:6]=2)([C:10]#[N:11])[CH2:13]1

Participants

Conditions

Temperature: 60 °C

Procedure

To a stirred suspension of NaH (1.466 g, 36.6 mmol, 60% in mineral oil) in DMF (25 mL) was added 2-(pyridin-3-yl)acetonitrile (1.954 mL, 18.32 mmol) followed by 1,3-dibromo-2,2-dimethoxypropane (4 g, 15.27 mmol) and the reaction mixture was warmed to 60° C. and stirred for 12 h. The reaction mixture was cooled to RT, poured into water (250 mL) and extracted with EtOAc (3×50 mL). The organic layer was separated, washed with water, brine, dried over Na2SO4, filtered and the filtrate concentrated. The crude product was purified by silica gel chromatography (40 g REDISEP® column, eluting with 50% EtOAc in hexanes). Fractions containing the product were combined and evaporated to afford Intermediate 311A as a white solid (2 g, 60%). MS(ES): m/z=219.2 [M+H]+; 1H NMR (300 MHz, DMSO-d6) δ ppm 8.71 (dd, J=0.8, 2.6 Hz, 1H), 8.58 (dd, J=1.7, 4.7 Hz, 1H), 7.89 (s, 1H), 7.51-7.45 (m, 1H), 3.19 (s, 3H), 3.08 (s, 3H), 2.89 (s, 1H), 2.83 (s, 1H), 2.78 (s, 1H), 2.73 (d, J=0.8 Hz, 1H).

Workup

temperatureThe reaction mixture was cooled to RT
extractionextracted with EtOAc (3×50 mL)
customThe organic layer was separated
washwashed with water, brine
dry with materialdried over Na2SO4
filtrationfiltered
concentrationthe filtrate concentrated
customThe crude product was purified by silica gel chromatography (40 g REDISEP® column, eluting with 50% EtOAc in hexanes)
additionFractions containing the product
customevaporated

Sources & evidence

ORD record: ord-7ecb7af7382c43aca8758ba638fc174d
Source dataset: uspto-grants-2016_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09273058B2

Reaction notes

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