4-Piperidinecarboxylic acid → 1-(4-(5-(5-amino-6-(5-tert-butyl-1,3,4-oxadiazol-2-yl)pyrazin-2-yl)-1-methyl-1H-1,2,4-triazol-3-yl)piperidin-1-yl)-3-hydroxypropan-1-one

HRID 1749676Notes

Reaction equation

HRID 1749676 reaction equation
[C:1]([N:8]1[CH2:16][CH2:15][CH:11]([C:12](O)=O)[CH2:10][CH2:9]1)([O:3]C(C)(C)C)=O.N1CC[CH:20]([C:21](O)=[O:22])CC1.[CH3:26]N1CCOCC1.ClC(OCC(C)C)=O.[NH2:41][C:42]1[N:43]=[CH:44][C:45](/[C:57](=[N:59]/[NH2:60])/[NH2:58])=[N:46][C:47]=1[C:48]1[O:49][C:50]([C:53]([CH3:56])([CH3:55])[CH3:54])=[N:51][N:52]=1>CC(N(C)C)=O.O>[NH2:41][C:42]1[N:43]=[CH:44][C:45]([C:57]2[N:59]([CH3:26])[N:60]=[C:12]([CH:11]3[CH2:10][CH2:9][N:8]([C:1](=[O:3])[CH2:20][CH2:21][OH:22])[CH2:16][CH2:15]3)[N:58]=2)=[N:46][C:47]=1[C:48]1[O:49][C:50]([C:53]([CH3:54])([CH3:55])[CH3:56])=[N:51][N:52]=1

Participants

8

Reactant 5

HCID 37734-Piperidinecarboxylic acidHCID 79724-MethylmorpholineHCID 62365Isobutyl chloroformateHCID 3928711-(tert-Butoxycarbonyl)-4-piperidinecarboxylic acidHCID 90283262N',5-diamino-6-(5-tert-butyl-1,3,4-oxadiazol-2-yl)pyrazine-2-carboximidamide

Product 1

HCID 867276631-(4-(5-(5-amino-6-(5-tert-butyl-1,3,4-oxadiazol-2-yl)pyrazin-2-yl)-1-methyl-1H-1,2,4-triazol-3-yl)piperidin-1-yl)-3-hydroxypropan-1-one

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 31374DimethylacetamideSolvent

Procedure

In an alternative preparation, the N-Boc-isonipecotic acid may be made in situ as follows: Isonipecotic acid (858 g, 3.74 mol) was dissolved in DMA (25.3 L) and 4-methylmorpholine (393 mL, 3.74 mol) added. Stirred for 5 mins and isobutyl chloroformate (489 mL, 3.74 mol) added. The reaction mixture was stirred at 25° C. for 2 h and cooled to 15° C. before (Z)-5-amino-6-(5-tert-butyl-1,3,4-oxadiazol-2-yl)pyrazine-2-carbohydrazonamide (940 g, 3.4 mol) was added portionwise over 10 mins. The reaction mixture was stirred for 1-2 h at 15° C. Water (20.5 L) was added portionwise over 1 h and stirred for a further 1 h before being filtered. The filtercake was then washed with water (4×4 L) and pulled dry on the filter before being dried in a vacuum oven at 50° C. until dry to give the desired product.

Workup

  1. customIn an alternative preparation
  2. stirringThe reaction mixture was stirred at 25° C. for 2 h
  3. additionwas added portionwise over 10 mins
  4. stirringThe reaction mixture was stirred for 1-2 h at 15° C
  5. stirringstirred for a further 1 h
  6. filtrationbefore being filtered
  7. washThe filtercake was then washed with water (4×4 L)
  8. custompulled dry on the
  9. filtrationfilter
  10. custombefore being dried in a vacuum oven at 50° C.
  11. customuntil dry

Sources & evidence

ORD record
ord-8fa44db09b804aa6b1b90d37eacf8986
Source dataset
uspto-grants-2015_10
Patent number
US09156831B2

Reaction notes

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