Cyanogen Bromide → 4-(1-(5-(5-Amino-1,3,4-oxadiazol-2-yl)-4-cyclobutyl-2-ethylbenzoyl)piperidin-4-yl)benzonitrile

HRID 541349Notes

Reaction equation

HRID 541349 reaction equation
[C:1]([C:3]1[CH:8]=[CH:7][C:6]([CH:9]2[CH2:14][CH2:13][N:12]([C:15]([C:17]3[C:18]([CH2:31][CH3:32])=[CH:19][C:20]([CH:27]4[CH2:30][CH2:29][CH2:28]4)=[C:21]([CH:26]=3)[C:22]([NH:24][NH2:25])=[O:23])=[O:16])[CH2:11][CH2:10]2)=[CH:5][CH:4]=1)#[N:2].C(=O)(O)[O-].[Na+].[N:38]#[C:39]Br>O1CCOCC1>[NH2:38][C:39]1[O:23][C:22]([C:21]2[C:20]([CH:27]3[CH2:30][CH2:29][CH2:28]3)=[CH:19][C:18]([CH2:31][CH3:32])=[C:17]([CH:26]=2)[C:15]([N:12]2[CH2:11][CH2:10][CH:9]([C:6]3[CH:5]=[CH:4][C:3]([C:1]#[N:2])=[CH:8][CH:7]=3)[CH2:14][CH2:13]2)=[O:16])=[N:24][N:25]=1

Participants

5

Reactant 3

HCID 10476Cyanogen BromideHCID 516892Sodium BicarbonateHCID 682884435-(4-(4-Cyanophenyl)piperidine-1-carbonyl)-2-cyclobutyl-4-ethylbenzohydrazide2×

Product 1

HCID 682883904-(1-(5-(5-Amino-1,3,4-oxadiazol-2-yl)-4-cyclobutyl-2-ethylbenzoyl)piperidin-4-yl)benzonitrile

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
25 °C

Procedure

To a solution of 5-(4-(4-cyanophenyl)piperidine-1-carbonyl)-2-cyclobutyl-4-ethylbenzohydrazide (compound 215.6, 600 mg, 1.39 mmol, 1.00 equiv) in 1,4-dioxane (10 mL) was added 10 mL of an aqueous solution of sodium bicarbonate (350 mg, 4.17 mmol, 1.00 equiv). Cyanogen bromide (220 mg, 2.08 mmol, 1.50 equiv) was added to the reaction mixture dropwise. The reaction mixture was stirred at 25° C. for 2 h, then quenched with 20 mL of FeSO4 (aq., sat.) and diluted with DCM. The resulting mixture was stirred vigorously then filtered through celite and washed with 1 M FeSO4, water, and ethyl acetate. The layers were separated and the aqueous phase was extracted with 2×50 mL of DCM. The combined organic layers were dried over anhydrous sodium sulfate and concentrated in vacuo. This resulted in 600 mg (95%) of 4-(1-(5-(5-amino-1,3,4-oxadiazol-2-yl)-4-cyclobutyl-2-ethylbenzoyl)piperidin-4-yl)benzonitrile as an off-white solid.

Workup

  1. customquenched with 20 mL of FeSO4 (aq., sat.)
  2. additiondiluted with DCM
  3. stirringThe resulting mixture was stirred vigorously
  4. filtrationthen filtered through celite
  5. washwashed with 1 M FeSO4, water, and ethyl acetate
  6. customThe layers were separated
  7. extractionthe aqueous phase was extracted with 2×50 mL of DCM
  8. dry with materialThe combined organic layers were dried over anhydrous sodium sulfate
  9. concentrationconcentrated in vacuo
  10. customThis resulted in 600 mg (95%) of 4-(1-(5-(5-amino-1,3,4-oxadiazol-2-yl)-4-cyclobutyl-2-ethylbenzoyl)piperidin-4-yl)benzonitrile as an off-white solid

Sources & evidence

ORD record
ord-041e2d1b8d3c45a085a98177b6367bad
Source dataset
uspto-grants-2014_10
Patent number
US08871790B2

Reaction notes

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