Formaldehyde → (S)-2-(4-chlorophenyl)-2-((S)-1-methylpyrrolidin-2-yl)-1-(4-(5-phenyl-1H-pyrrolo[2,3-b]pyridin-4-yl)piperazin-1-yl)ethanone dihydrochloride

HRID 79569ノート

反応式

HRID 79569 の反応式
[ClH:1].Cl.[Cl:3][C:4]1[CH:9]=[CH:8][C:7]([C@@H:10]([C@@H:34]2[CH2:38][CH2:37][CH2:36][NH:35]2)[C:11]([N:13]2[CH2:18][CH2:17][N:16]([C:19]3[C:24]([C:25]4[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=4)=[CH:23][N:22]=[C:21]4[NH:31][CH:32]=[CH:33][C:20]=34)[CH2:15][CH2:14]2)=[O:12])=[CH:6][CH:5]=1.C=O.[BH3-][C:42]#N.[Na+].CN.C([O-])(O)=O.[Na+]>CO>[ClH:3].[ClH:1].[Cl:3][C:4]1[CH:5]=[CH:6][C:7]([C@@H:10]([C@@H:34]2[CH2:38][CH2:37][CH2:36][N:35]2[CH3:42])[C:11]([N:13]2[CH2:14][CH2:15][N:16]([C:19]3[C:24]([C:25]4[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=4)=[CH:23][N:22]=[C:21]4[NH:31][CH:32]=[CH:33][C:20]=34)[CH2:17][CH2:18]2)=[O:12])=[CH:8][CH:9]=1

参加物

7

反応物 5

HCID 712FormaldehydeHCID 6329MethylamineHCID 516892Sodium BicarbonateHCID 5003444Sodium cyanoborohydrideHCID 68760830(S)-2-(4-chlorophenyl)-1-(4-(5-phenyl-1H-pyrrolo[2,3-b]pyri din-4-yl)piperazin-1-yl)-2-((S)-pyrrolidin-2-yl)ethanone dihydrochloride

生成物 1

HCID 68761411(S)-2-(4-chlorophenyl)-2-((S)-1-methylpyrrolidin-2-yl)-1-(4-(5-phenyl-1H-pyrrolo[2,3-b]pyridin-4-yl)piperazin-1-yl)ethanone dihydrochloride収率 194.7%

試薬・触媒・溶媒 1

HCID 887Methanol溶媒

実験手順

(S)-2-(4-Chlorophenyl)-1-(4-(5-phenyl-1H-pyrrolo[2,3-b]pyridin-4-yl)piperazin-1-yl)-2-((S)-pyrrolidin-2-yl)ethanone dihydrochloride (0.060 g, 0.105 mmol, see Example 20) in MeOH (0.5 mL) was cooled to a temperature of about 0° C. to about 5° C. Formaldehyde (0.0234 mL, 0.314 mmol) and NaCNBH3 (0.0132 g, 0.210 mmol) were added. The mixture was stirred at a temperature of about 14° C. to about 16° C. for 45 minutes. Methyl amine (2 mL, 2.0M in THF) was added, and the reaction was stirred for 30 minutes. Saturated NaHCO3 (5 mL) was added, and the aqueous phase was extracted with DCM (20 mL). The combined organic phases were washed with brine (10 mL), and dried over sodium sulfate. After removal of the solvent, the resulting residue was dissolved in DCM (0.5 mL), and 2M HCl in ether (1 mL) was added. The resulting solid was collected by filtration to give (S)-2-(4-chlorophenyl)-2-((S)-1-methylpyrrolidin-2-yl)-1-(4-(5-phenyl-1H-pyrrolo[2,3-b]pyridin-4-yl)piperazin-1-yl)ethanone dihydrochloride (0.060 g, 98%). MS ESI (+) m/z 514 detected.

後処理

  1. stirringthe reaction was stirred for 30 minutes
  2. extractionthe aqueous phase was extracted with DCM (20 mL)
  3. washThe combined organic phases were washed with brine (10 mL)
  4. dry with materialdried over sodium sulfate
  5. customAfter removal of the solvent
  6. dissolutionthe resulting residue was dissolved in DCM (0.5 mL)
  7. addition2M HCl in ether (1 mL) was added
  8. filtrationThe resulting solid was collected by filtration

出典と根拠

ORDレコード
ord-25ad813f970045568ac3633cbe95dd9b
出典データセット
uspto-grants-2014_09
特許番号
US08841304B2

反応ノート

読み込み中…