Isoamylamine → HCID 59750685, compound

HRID 422255Notes

Reaction equation

HRID 422255 reaction equation
[CH:1]([CH:3]1[CH2:11][C:10]2[C:5](=[CH:6][CH:7]=[C:8]([O:12][C:13]3[CH:21]=[CH:20][C:16]([C:17]([NH2:19])=[O:18])=[CH:15][N:14]=3)[CH:9]=2)[CH2:4]1)=O.COC(OC)OC.[CH2:29]([NH2:34])[CH2:30][CH:31]([CH3:33])[CH3:32]>CO>[CH3:32][CH:31]([CH3:33])[CH2:30][CH2:29][NH:34][CH2:1][CH:3]1[CH2:11][C:10]2[C:5](=[CH:6][CH:7]=[C:8]([O:12][C:13]3[CH:21]=[CH:20][C:16]([C:17]([NH2:19])=[O:18])=[CH:15][N:14]=3)[CH:9]=2)[CH2:4]1

Participants

5

Reactant 3

HCID 7894IsoamylamineHCID 9005Trimethyl orthoformateHCID 59750672HCID 59750672, compound2×

Product 1

HCID 59750685HCID 59750685, compoundYield 25%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

Combine 6-(2-Formyl-indan-5-yloxy)-nicotinamide (Intermediate 32, 25.3 mg, 0.09 mmol), MeOH (2.4 mL), trimethylorthoformate (1.6 mL), and isopentyl amine (9 uL, 0.08 mmol). After the reaction stirs at room temperature under a nitrogen atmosphere for 4.5 hours, add NaBH (4.1 mg, 0.11 mmol), then stir at room temperature for another 12 hours. After that time, concentrate under reduced pressure then add ethyl acetate. Wash the organic phase with water, brine, and dry over Na2SO4. After concentration under reduced pressure the mixture, add to a 2 g SCX column, wash with MeOH and elute with 1N NH3-MeOH. After concentration, flash chromatograph using 2% 1N NH3-MeOH, 20% THF, 38% DCM to afford 7.0 mg, 0.02 mmol (25% yield) of the title compound: 1H NMR (500 MHz, d-Methanol); 0.9 (6H, d), 1.4-1.5 (2H, m), 1.6-1.7 (1H, m), 2.6-2.8 (6H, m), 3.1-3.2 (2H, m), 3.3-3.4 (1H, m), 6.8 (1H, d), 6.9 (1H, s), 7.1 (1H, d), 7.2 (1H, d), 8.1 (1H, d), 8.5 (1H, s); TLC 2% 1N NH3-MeOH:20% THF:78% CH2Cl2:Rf:=0.27.

Workup

  1. concentrationAfter that time, concentrate under reduced pressure
  2. washWash the organic phase with water, brine
  3. dry with materialdry over Na2SO4
  4. concentrationAfter concentration under reduced pressure the mixture
  5. additionadd to a 2 g SCX column
  6. washwash with MeOH
  7. washelute with 1N NH3-MeOH
  8. concentrationAfter concentration, flash chromatograph

Sources & evidence

ORD record
ord-5ac4f5b0d6204d93bf56e62913d955f3
Source dataset
uspto-grants-2012_01
Patent number
US08101638B2

Reaction notes

Loading…