Acetic Acid → HCID 22100877, compound

HRID 1458367Notes

Reaction equation

HRID 1458367 reaction equation
[CH3:1][C:2]1[CH:3]=[C:4]([C:9]2[NH:10][C:11]3[C:16]([C:17]=2[CH2:18][CH2:19][NH:20][CH2:21][CH2:22][CH2:23][CH2:24]C2C=NC=CC=2)=[CH:15][C:14]([C:31]([CH3:44])([CH3:43])[C:32]([N:34]([CH2:39][CH2:40][CH2:41][CH3:42])[CH2:35][CH2:36][CH2:37][CH3:38])=[O:33])=[CH:13][CH:12]=3)[CH:5]=[C:6]([CH3:8])[CH:7]=1.C=O.[C:47](O)(=O)C.[C:51]([BH3-])#[N:52].[Na+].[CH2:55]1[CH2:59]O[CH2:57][CH2:56]1>CO>[CH3:8][C:6]1[CH:5]=[C:4]([C:9]2[NH:10][C:11]3[C:16]([C:17]=2[CH2:18][CH2:19][N:20]([CH3:47])[CH2:21][CH2:22][CH2:23][CH2:24][C:55]2[CH:59]=[CH:51][N:52]=[CH:57][CH:56]=2)=[CH:15][C:14]([C:31]([CH3:44])([CH3:43])[C:32]([N:34]([CH2:39][CH2:40][CH2:41][CH3:42])[CH2:35][CH2:36][CH2:37][CH3:38])=[O:33])=[CH:13][CH:12]=3)[CH:3]=[C:2]([CH3:1])[CH:7]=1

Participants

7

Reactant 5

HCID 176Acetic AcidHCID 712FormaldehydeHCID 8028TetrahydrofuranHCID 5003444Sodium cyanoborohydrideHCID 22100891HCID 22100891, compound

Product 1

HCID 22100877HCID 22100877, compoundYield 45%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A dry flask containing 67 mg (0.113 mmol) of 2-[2-(3,5-dimethylphenyl)-3-[2-[methyl-[4-(pyridin-4-yl)butyl]amino]ethyl]-1H-indol-5-yl]-N,N-dibutylisobutyramide (prepared according to EXAMPLE 7.2), 33.9 mg (1.3 mmol) of paraformaldehyde, and 100 mg of powdered 3A molecular sieves was fitted with a septum and purged thoroughly with N2. Next, 2.65 mL of MeOH and 65.2 μL (67.8 mg, 1.13 mmol) of glacial acetic acid were added, and the mixture was stirred at room temperature for 35 minutes. Then 28.4 mg (0.452 mmol) of sodium cyanoborohydride was added, followed after an additional 20 minutes by 2.5 mL of anhydrous THF. After a few minutes, TLC indicated complete reaction. Therefore, the mixture was filtered, and the filtrate was shaken in a separatory funnel with brine. The aqueous phase was extracted an additional 3 times with CH2Cl2. The combined organic fractions were dried over Na2SO4, 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. NH4OH) to yield 31.1 mg (45%) of the title compound as a glass; homogeneous by TLC in 95:5:0.5 CH2Cl2 -MeOH-concd. NH4OH. 500 MHz 1H NMR (CDCl3) was consistent with the assigned structure. m/e=609.5 (M+H).

Workup

  1. customwas fitted with a septum
  2. custompurged thoroughly with N2
  3. waitAfter a few minutes
  4. customreaction
  5. filtrationTherefore, the mixture was filtered
  6. stirringthe filtrate was shaken in a separatory funnel with brine
  7. extractionThe aqueous phase was extracted an additional 3 times with CH2Cl2
  8. dry with materialThe combined organic fractions were dried over Na2SO4
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo
  11. customchromatographed on silica gel (gradient elution with 99:1:0.1 to 95:5:0.5 CH2Cl2 -MeOH-concd. NH4OH)

Sources & evidence

ORD record
ord-49172278bdf94f81ada4246b62f83096
Source dataset
uspto-grants-1998_12
Patent number
US05849764

Reaction notes

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