Pyridine, hydrofluoride (1:1) → HCID 71043121, compound

HRID 1501880Notes

Reaction equation

HRID 1501880 reaction equation
[Si]([O:8][C@H:9]1[CH2:14][CH2:13][CH2:12][CH2:11][C@@H:10]1[N:15]1[CH:23]([CH3:24])[C:22]2[C:21]3[CH:25]=[CH:26][CH:27]=[CH:28][C:20]=3[C:19]([CH2:29][N:30]3[CH2:35][CH2:34][C:33]([C:38]4[CH:43]=[CH:42][CH:41]=[CH:40][N:39]=4)([C:36]#[N:37])[CH2:32][CH2:31]3)=[CH:18][C:17]=2[C:16]1=[O:44])(C(C)(C)C)(C)C.N1C=CC=CC=1.F.C(=O)(O)[O-].[Na+]>N1C=CC=CC=1>[OH:8][C@H:9]1[CH2:14][CH2:13][CH2:12][CH2:11][C@@H:10]1[N:15]1[CH:23]([CH3:24])[C:22]2[C:21]3[CH:25]=[CH:26][CH:27]=[CH:28][C:20]=3[C:19]([CH2:29][N:30]3[CH2:31][CH2:32][C:33]([C:38]4[CH:43]=[CH:42][CH:41]=[CH:40][N:39]=4)([C:36]#[N:37])[CH2:34][CH2:35]3)=[CH:18][C:17]=2[C:16]1=[O:44]

Participants

5

Reactant 3

HCID 64774Pyridine, hydrofluoride (1:1)HCID 516892Sodium BicarbonateHCID 123444541HCID 123444541, compound

Product 1

HCID 71043121HCID 71043121, compound

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Procedure

To a solution of 1-({2-[(1S,2S)-2-{[tert-butyl(dimethyl)silyl]oxy}cyclohexyl]-1-methyl-3-oxo-2,3-dihydro-1H-benzo[e]isoindol-5-yl}methyl)-4-(pyridin-2-yl)piperidine-4-carbonitrile (0.120 g, 0.197 mmol) in 0.1 mL of pyridine was added hydrogen fluoride pyridine (0.098 g, 0.98 mmol). After 15 hr, the mixture was treated with saturated aqueous sodium bicarbonate and extracted 2× with ethyl acetate. The combined organic extracts were washed with brine, dried with magnesium sulfate, filtered, and concentrated in vacuo. The residue was purified via silica gel chromatography, eluting with 10-100% ethyl acetate in hexanes, to provide the titled compound that gave a proton NMR spectra consistent with theory and a mass ion (ES+) of 495.2765 for [M+H]+ [calc'd for C31H35N4O2, [M+H]+=495.2755]: 1H NMR (400 MHz, CDCl3) δ 8.60-8.58 (m, 1H), 8.45-8.41 (m, 1H), 7.95-7.90 (m, 1H), 7.83-7.79 (m, 1H), 7.74-7.69 (m, 1H), 7.66-7.56 (m, 3H), 7.25-7.21 (m, 1H), 5.11-5.03 (m, 2H), 4.42 (br s, 1H), 4.03-3.98 (m, 2H), 3.79-3.72 (m, 1H), 3.65-3.59 (m, 1H), 3.06-3.02 (m, 2H), 2.88-2.86 (m, 1H), 2.67-2.59 (m, 2H), 2.35-2.17 (m, 2H), 2.09-2.06 (m, 1H), 2.04-1.81 (m, 2H), 1.42-1.22 (m, 4H), 0.96-0.83 (m, 4H) ppm.

Workup

  1. extractionextracted 2× with ethyl acetate
  2. washThe combined organic extracts were washed with brine
  3. dry with materialdried with magnesium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified via silica gel chromatography
  7. washeluting with 10-100% ethyl acetate in hexanes

Sources & evidence

ORD record
ord-3db82e0564a5404aafef781a13ff9651
Source dataset
uspto-grants-2015_12
Patent number
US09206200B2

Reaction notes

Loading…