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 79569Notes

Reaction equation

HRID 79569 reaction equation
[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

Participants

7

Reactant 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

Product 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 dihydrochlorideYield 194.7%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

(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.

Workup

  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

Sources & evidence

ORD record
ord-25ad813f970045568ac3633cbe95dd9b
Source dataset
uspto-grants-2014_09
Patent number
US08841304B2

Reaction notes

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