Acetic Acid → HCID 44215055, compound

HRID 1532392Notes

Reaction equation

HRID 1532392 reaction equation
[CH:1]12[N:7]([C:8](=[O:42])[C:9]([C:12]3[CH:13]=[C:14]4[C:18](=[CH:19][CH:20]=3)[NH:17][C:16]([C:21]3[CH:26]=[C:25]([CH3:27])[CH:24]=[C:23]([CH3:28])[CH:22]=3)=[C:15]4[CH2:29][CH2:30][NH:31][CH2:32][CH2:33][CH2:34][CH2:35][C:36]3[CH:41]=[CH:40][N:39]=[CH:38][CH:37]=3)([CH3:11])[CH3:10])[CH:4]([CH2:5][CH2:6]1)[CH2:3][CH2:2]2.C=O.[C:45](O)(=O)C.C([BH3-])#N.[Na+].[NH4+].[OH-]>O1CCCC1.CO>[CH:4]12[N:7]([C:8](=[O:42])[C:9]([C:12]3[CH:13]=[C:14]4[C:18](=[CH:19][CH:20]=3)[NH:17][C:16]([C:21]3[CH:22]=[C:23]([CH3:28])[CH:24]=[C:25]([CH3:27])[CH:26]=3)=[C:15]4[CH2:29][CH2:30][N:31]([CH3:45])[CH2:32][CH2:33][CH2:34][CH2:35][C:36]3[CH:41]=[CH:40][N:39]=[CH:38][CH:37]=3)([CH3:11])[CH3:10])[CH:1]([CH2:2][CH2:3]1)[CH2:6][CH2:5]2

Participants

8

Reactant 5

HCID 176Acetic AcidHCID 712FormaldehydeHCID 14923Ammonium HydroxideHCID 5003444Sodium cyanoborohydrideHCID 44293249HCID 44293249, compound

Product 1

HCID 44215055HCID 44215055, compound

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

A dry flask containing 120 mg (0.21 mmol) of 1-(7-azabicyclo[2.2.1]hept-7-yl)-2-[2-(3,5-dimethylphenyl)-3-[2-[4-(pyridin-4-yl)butylamino]ethyl]-1H-indol-5-yl)-2-methylpropan-1-one (prepared essentially as described in EXAMPLE 2), 63.0 mg (2.1 mmol) of paraformaldehyde, and 200 mg of powdered 3A molecular sieves was fitted with a septum and purged thoroughly with nitrogen. Next, 5 mL of methanol and 0.121 mL (126.1 mg, 2.1 mmol) of glacial acetic acid were added, and the mixture was stirred at room temperature for 15 minutes. Then 52.8 mg (0.84 mmol) of sodium cyanoborohydride was added, followed after an additional 25 minutes by 2.5 mL of anhydrous tetrahydrofuran. After 1 day, the mixture was filtered, and the filter cake was washed thoroughly with methylene chloride. The filtrate was shaken in a separatory funnel with water. The aqueous phase was extracted an additional 3 times with methylene chloride. The combined organic fractions were dried over sodium sulfate, filtered, and concentrated in vacuo. The residue was flash chromatographed on silica gel (gradient elution with 99:1:0.1 to 95:5:0.5 CH2Cl2-MeOH-concd. NH4O) to yield 95.4 mg (79%) of a yellow, stiff foam; homogeneous by TLC in 95:5:0.5 CH2Cl2-MeOH-concd. NH4OH. 500 MHz 1H NMR (CDCl3) was consistent with the assigned structure. Mass spectrum (ESI): m/e=577.5 (M+H).

Workup

  1. customprepared essentially
  2. customwas fitted with a septum
  3. custompurged thoroughly with nitrogen
  4. waitAfter 1 day
  5. filtrationthe mixture was filtered
  6. washthe filter cake was washed thoroughly with methylene chloride
  7. stirringThe filtrate was shaken in a separatory funnel with water
  8. extractionThe aqueous phase was extracted an additional 3 times with methylene chloride
  9. dry with materialThe combined organic fractions were dried over sodium sulfate
  10. filtrationfiltered
  11. concentrationconcentrated in vacuo
  12. customchromatographed on silica gel (gradient elution with 99:1:0.1 to 95:5:0.5 CH2Cl2-MeOH-concd. NH4O)
  13. customto yield 95.4 mg (79%) of a yellow, stiff foam

Sources & evidence

ORD record
ord-b77ce27f10de46a8a560583e3926d13f
Source dataset
uspto-grants-2001_03
Patent number
US06200957B1

Reaction notes

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