Diisopropylethylamine → 2-(4-{[(4-Bromo-5-methyl-1H-pyrrol-2-yl)carbonyl]amino}piperidin-1-yl)-6-chloroisonicotinamide

HRID 2233937Notes

Reaction equation

HRID 2233937 reaction equation
Cl.O1CCOCC1.[NH2:8][C:9]([C:11]1[CH:16]=[C:15]([Cl:17])[N:14]=[C:13]([N:18]2[CH2:23][CH2:22][CH:21]([NH:24][C:25](=[O:31])OC(C)(C)C)[CH2:20][CH2:19]2)[CH:12]=1)=[O:10].[Br:32][C:33]1[CH:34]=[C:35](C(OC2C(F)=C(F)C(F)=C(F)C=2F)=O)[NH:36][C:37]=1[CH3:38].C(N(CC)C(C)C)(C)C.Cl.NC1CCN(C2C=C(C=C(Cl)N=2)C(N)=O)CC1>CC(N(C)C)=O>[Br:32][C:33]1[CH:34]=[C:35]([C:25]([NH:24][CH:21]2[CH2:20][CH2:19][N:18]([C:13]3[CH:12]=[C:11]([CH:16]=[C:15]([Cl:17])[N:14]=3)[C:9]([NH2:8])=[O:10])[CH2:23][CH2:22]2)=[O:31])[NH:36][C:37]=1[CH3:38]

Participants

7

Reactant 5

HCID 81531DiisopropylethylamineHCID 204431481,4-Dioxane hydrochlorideHCID 86608240tert-Butyl 1-[4-(aminocarbonyl)-6-chloropyridin-2-yl]piperidin-4-ylcarbamate2×HCID 86608241Pentafluorophenyl 4-bromo-5-methyl-1H-pyrrole-2-carboxylate2×HCID 866082552-(4-Aminopiperidin-1-yl)-6-chloroisonicotinamide hydrochloride

Product 1

HCID 114193192-(4-{[(4-Bromo-5-methyl-1H-pyrrol-2-yl)carbonyl]amino}piperidin-1-yl)-6-chloroisonicotinamideYield 22.5%

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent

Procedure

4 N HCl/dioxane solution (10 ml) was added to tert-butyl 1-[4-(aminocarbonyl)-6-chloropyridin-2-yl]piperidin-4-ylcarbamate (Intermediate 16, 100 mg, 0.282 mmol). The mixture was stirred at room temperature for 90 minutes. The solvent was removed in vacuo and the anhydrous diethylether (25 ml) was added. The solvent was removed in vacuo and light brown solid that resulted was dried under vacuum for several hours. LCMS indicated a pure product 2-(4-aminopiperidin-1-yl)-6-chloroisonicotinamide hydrochloride salt (MS M+H:255). Pentafluorophenyl 4-bromo-5-methyl-1H-pyrrole-2-carboxylate (Intermediate 17) (104 mg, 0.282 mmol), and N,N-diisopropyl ethylamine (98 μl, 0.564 mmol) were added to 2-(4-aminopiperidin-1-yl)-6-chloroisonicotinamide hydrochloride salt (82 mg, 0.282 mmol) in anhydrous DMA (4 ml). The mixture was stirred at room temperature 18 h and was filtered and purified by semi-preparative HPLC using CH3CN/H2O (0.1% TFA) to give the title compound (28 mg).

Workup

  1. customThe solvent was removed in vacuo
  2. additionthe anhydrous diethylether (25 ml) was added
  3. customThe solvent was removed in vacuo and light brown solid that
  4. customresulted
  5. customwas dried under vacuum for several hours
  6. stirringThe mixture was stirred at room temperature 18 h
  7. filtrationwas filtered
  8. custompurified by semi-preparative HPLC

Sources & evidence

ORD record
ord-6edce334ea5945b1963306249d8718c9
Source dataset
uspto-grants-2010_05
Patent number
US07709503B2

Reaction notes

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