Pyridine → HCID 68543933, compound

HRID 2388567Notes

Reaction equation

HRID 2388567 reaction equation
[Cl:1][C:2]1[C:9]([CH3:10])=[C:8]([NH:11][C@@H:12]([C:16]2[O:17][C:18]([C:21]3[CH:26]=[CH:25][C:24]([C:27]#[N:28])=[CH:23][CH:22]=3)=[N:19][N:20]=2)[C@@H:13]([OH:15])[CH3:14])[CH:7]=[CH:6][C:3]=1[C:4]#[N:5].N1C=CC=CC=1.[C:35](Cl)(=[O:39])[CH2:36][CH2:37][CH3:38]>C(Cl)Cl>[C:35]([O:15][C@@H:13]([CH3:14])[C@@H:12]([NH:11][C:8]1[CH:7]=[CH:6][C:3]([C:4]#[N:5])=[C:2]([Cl:1])[C:9]=1[CH3:10])[C:16]1[O:17][C:18]([C:21]2[CH:22]=[CH:23][C:24]([C:27]#[N:28])=[CH:25][CH:26]=2)=[N:19][N:20]=1)(=[O:39])[CH2:36][CH2:37][CH3:38]

Participants

5

Reactant 3

HCID 1049PyridineHCID 8855Butyryl chlorideHCID 44200882RAD140

Product 1

HCID 68543933HCID 68543933, compoundYield 60%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a 50 mL round bottomed flask was added 2-chloro-4-((1R,2S)-1-(5-(4-cyanophenyl)-1,3,4-oxadiazol-2-yl)-2-hydroxypropylamino)-3-methylbenzonitrile (200 mg, 0.508 mmol, pyridine (1 mL, 12.41 mmol) and methylene chloride (15 mL). Butyryl chloride (0.26 mL, 2.54 mmol) was then added dropwise and the mixture was stirred at room temperature for 18 h. The reaction mixture was then quenched with 10% aq HCl (15 mL) and methylene chloride (30 mL) was added. The phases were partitioned and the aqueous phase extracted with methylene chloride (30 mL) (×2). The combined organics were washed with a saturated solution of sodium hydrogen carbonate, dried (Na2SO4) and concentrated to furnish a yellow oil (0.139 g, 60%). 1H NMR (Acetone d6, 400 MHz) δ 8.23 (d, J=9 Hz, 2H), 8.02 (d, J=9 Hz, 1H), 7.54 (d, J=9 Hz, 1H), 7.02 (d, J=9 Hz, 1H), 5.74 (d, J=9 Hz, 1H), 5.72-5.64 (m, 1H), 5.48 (dd, J=5 and 8 Hz, 1H), 2.37 (s, 3H), 2.33-2.25 (m, 2H), 1.64-1.50 (m, 2H), 1.47 (d, J=6 Hz, 3H) and 0.92 (t, J=8 Hz, 3H).

Workup

  1. customThe reaction mixture was then quenched with 10% aq HCl (15 mL) and methylene chloride (30 mL)
  2. additionwas added
  3. customThe phases were partitioned
  4. extractionthe aqueous phase extracted with methylene chloride (30 mL) (×2)
  5. washThe combined organics were washed with a saturated solution of sodium hydrogen carbonate
  6. dry with materialdried (Na2SO4)
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-4790bea8beca4762ac41f739d18eb97c
Source dataset
uspto-grants-2012_09
Patent number
US08268872B2

Reaction notes

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