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

HRID 2233937ノート

反応式

HRID 2233937 の反応式
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]

参加物

7

反応物 5

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

生成物 1

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

試薬・触媒・溶媒 1

HCID 31374Dimethylacetamide溶媒

実験手順

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).

後処理

  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

出典と根拠

ORDレコード
ord-6edce334ea5945b1963306249d8718c9
出典データセット
uspto-grants-2010_05
特許番号
US07709503B2

反応ノート

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