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

HRID 2233937노트

반응식

HRID 2233937 반응식
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]

참가 물질

7

반응물 5

HCID 81531DiisopropylethylamineHCID 204431481,4-Dioxane hydrochlorideHCID 86608240tert-Butyl 1-[4-(aminocarbonyl)-6-chloropyridin-2-yl]piperidin-4-ylcarbamate2회HCID 86608241Pentafluorophenyl 4-bromo-5-methyl-1H-pyrrole-2-carboxylate2회HCID 866082552-(4-Aminopiperidin-1-yl)-6-chloroisonicotinamide hydrochloride

생성물 1

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

시약·촉매·용매 1

HCID 31374Dimethylacetamide용매

실험 절차

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).

후처리

  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

출처 및 근거

ORD 기록
ord-6edce334ea5945b1963306249d8718c9
출처 데이터셋
uspto-grants-2010_05
특허 번호
US07709503B2

반응 노트

불러오는 중…