Pyridine → HCID 178458726, compound

HRID 1430987Notes

Reaction equation

HRID 1430987 reaction equation
[CH:1]([O:4][C:5]1[CH:6]=[C:7]([CH:11]=[C:12]([O:14][CH2:15][CH2:16][C:17]2[CH:21]=[CH:20][S:19][CH:18]=2)[CH:13]=1)[C:8]([OH:10])=O)([CH3:3])[CH3:2].C(Cl)(=O)C(Cl)=O.[C:28]([SiH2:32][O:33][C:34]([CH3:43])([CH3:42])[C:35]1[CH:36]=[CH:37][C:38]([NH2:41])=[N:39][CH:40]=1)([CH3:31])([CH3:30])[CH3:29].N1C=CC=CC=1>C(Cl)Cl.CN(C=O)C>[C:28]([SiH2:32][O:33][C:34]([CH3:43])([CH3:42])[C:35]1[CH:36]=[CH:37][C:38]([NH:41][C:8](=[O:10])[C:7]2[CH:11]=[C:12]([O:14][CH2:15][CH2:16][C:17]3[CH:21]=[CH:20][S:19][CH:18]=3)[CH:13]=[C:5]([O:4][CH:1]([CH3:2])[CH3:3])[CH:6]=2)=[N:39][CH:40]=1)([CH3:31])([CH3:29])[CH3:30]

Participants

7

Reactant 4

HCID 1049PyridineHCID 65578Oxalyl chlorideHCID 585289133-Isopropoxy-5-(2-thiophen-3-yl-ethoxy)-benzoic acidHCID 178455437HCID 178455437, compound

Product 1

HCID 178458726HCID 178458726, compoundYield 36%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

3-Isopropoxy-5-(2-thiophen-3-yl-ethoxy)-benzoic acid (2.03 g, 6.61 mmol) was dissolved in DCM (33 mL) with DMF (0.05 mL), and cooled to 0° C. Oxalyl chloride (1.16 mL, 13.22 mmol) was added dropwise and the mixture was allowed to stir for 1.5 hours. The reaction mixture was concentrated under reduced pressure to remove residual oxalyl chloride. The yellow oil was re-dissolved in DCM (33 mL), and 5-(tert-butyl-dimethyl-silanyloxymethyl)-pyridin-2-ylamine (1.71 g, 7.17 mmol) and pyridine (0.86 mL, 10.5 mmol) were added. After 16 hours, the reaction mixture was concentrated under reduced pressure and partitioned in EtOAc (50 mL) and water (50 mL). The organic layer was rinsed with water (30 mL), and then a saturated sodium chloride solution (30 mL), dried over sodium sulfate, filtered, and concentrated to brown oil. After chromatography on silica gel with a gradient from 5-30% ethyl acetate-hexanes, N-[5-(tert-butyl-dimethyl-silanyloxymethyl)-pyridin-2-yl]-3-isopropoxy-5-(2-thiophen-3-yl-ethoxy)-benzamide (1.25 g, 36.0% yield) was obtained. 1H NMR (300 MHz, DMSO-d6): δ 10.65 (s, 1H), 8.25 (s, 1H), 8.05 (d, J=6.0 Hz, 1H), 7.65 (d, J=6.0 Hz, 1H), 7.40 (d, J=3.0 Hz, 1H), 7.25 (s, 1H), 7.15 (s, 1H), 7.10 (s, 1H), 7.05 (d, J=3.0 Hz, 1H), 6.60 (s, 1H), 4.65 (s, 2H), 4.60 (m, 1H), 4.15 (t, 2H), 2.95 (t, 2H), 1.05 (s, 3H), 1.0 (s, 3H), 0.85 (s, 9H), 0.00 (s, 6H); LCMS (m/z): 527.3 [C28H38N2O4SSi+H]+.

Workup

  1. concentrationThe reaction mixture was concentrated under reduced pressure
  2. customto remove residual oxalyl chloride
  3. dissolutionThe yellow oil was re-dissolved in DCM (33 mL)
  4. waitAfter 16 hours
  5. concentrationthe reaction mixture was concentrated under reduced pressure
  6. custompartitioned in EtOAc (50 mL)
  7. washThe organic layer was rinsed with water (30 mL)
  8. dry with materiala saturated sodium chloride solution (30 mL), dried over sodium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated to brown oil

Sources & evidence

ORD record
ord-b0e1a62873964d818ba1415caee5b0bd
Source dataset
uspto-grants-2015_01
Patent number
US08940927B2

Reaction notes

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