Pyridine → HCID 68544007, compound

HRID 470902Notes

Reaction equation

HRID 470902 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:37])[CH3:36]>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:37])[CH3:36]

Participants

5

Reactant 3

HCID 1049PyridineHCID 6367Acetyl chlorideHCID 44200882RAD140

Product 1

HCID 68544007HCID 68544007, compoundYield 24%

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). Acetyl chloride (0.18 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 (0.052 g, 24%). 1H NMR (Acetone d6, 400 MHz) δ 8.23 (d, J=9 Hz, 2 H), 8.02 (d, J=9 Hz, 2 H), 7.54 (d, J=9 Hz, 1 H), 7.01 (d, J=9 Hz, 1 H), 5.74 (d, J=9 Hz, 1 H), 5.68-5.62 (m, 1H), (dd, J=9 and 5 Hz, 1H), 2.37 (s, 3 H), 2.04 (s, 3H), 1.47 (d, J=6 Hz, 3 H).

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-434be4d26a634800bb58fd59cf721756
Source dataset
uspto-grants-2014_01
Patent number
US08629167B2

Reaction notes

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