4-(Pyridin-3-yl)benzaldehyde → 1-(7-Azabicyclo[2.2.1]hept-7-yl)-2-{2-(3,5-dimethylphenyl)-3-[2-(4-pyridin-3-yl-benzylamino)ethyl]-1H-indol-5-yl}-2-methylpropan-1-one

HRID 1603056Notes

Reaction equation

HRID 1603056 reaction equation
[NH2:1][CH2:2][CH2:3][C:4]1[C:12]2[C:7](=[CH:8][CH:9]=[C:10]([C:13]([CH3:24])([CH3:23])[C:14]([N:16]3[CH:20]4[CH2:21][CH2:22][CH:17]3[CH2:18][CH2:19]4)=[O:15])[CH:11]=2)[NH:6][C:5]=1[C:25]1[CH:30]=[C:29]([CH3:31])[CH:28]=[C:27]([CH3:32])[CH:26]=1.[N:33]1[CH:38]=[CH:37][CH:36]=[C:35]([C:39]2[CH:46]=[CH:45][C:42]([CH:43]=O)=[CH:41][CH:40]=2)[CH:34]=1.C([BH3-])#N.[Na+]>CC(C)[O-].[Ti+4].CC(C)[O-].CC(C)[O-].CC(C)[O-].C(O)(=O)C>[CH:17]12[N:16]([C:14](=[O:15])[C:13]([C:10]3[CH:11]=[C:12]4[C:7](=[CH:8][CH:9]=3)[NH:6][C:5]([C:25]3[CH:30]=[C:29]([CH3:31])[CH:28]=[C:27]([CH3:32])[CH:26]=3)=[C:4]4[CH2:3][CH2:2][NH:1][CH2:43][C:42]3[CH:41]=[CH:40][C:39]([C:35]4[CH:34]=[N:33][CH:38]=[CH:37][CH:36]=4)=[CH:46][CH:45]=3)([CH3:24])[CH3:23])[CH:20]([CH2:19][CH2:18]1)[CH2:21][CH2:22]2

Participants

6

Reactant 3

HCID 36930464-(Pyridin-3-yl)benzaldehydeHCID 5003444Sodium cyanoborohydrideHCID 117617912-[3-(2-Aminoethyl)-2-(3,5-dimethylphenyl)-1H-indol-5-yl]-1-(7-azabicyclo[2.2.1]hept-7-yl)-2-methyl-propan-1-one

Product 1

HCID 109848361-(7-Azabicyclo[2.2.1]hept-7-yl)-2-{2-(3,5-dimethylphenyl)-3-[2-(4-pyridin-3-yl-benzylamino)ethyl]-1H-indol-5-yl}-2-methylpropan-1-oneYield 28.8%

Reagents, catalysts & solvents 2

HCID 11026Titanium isopropoxideCatalystHCID 176Acetic AcidSolvent

Procedure

To a solution of 2-[3-(2-aminoethyl)-2-(3,5-dimethylphenyl)-1H-indol-5-yl]-1-(7-azabicyclo[2.2.1]hept-7-yl)-2-methyl-propan-1-one (20 mg in 1.5 mL dry, degassed tetrahydrofuran) was added 9.4 mg 4-pyridin-3-yl-benzaldehyde followed by 43 mg titanium (IV) isopropoxide and the mixture stirred at room temperature. After 60 hours, the reaction was cooled to 0° C. and a solution of sodium cyanoborohydride (9.0 mg in 0.50 mL methanol) was added along with 0.026 mL acetic acid and the mixture stirred at low temperature. The reaction was quenched after 45 minutes by the addition of saturated aqueous ammonium chloride and brine. This was then extracted with ethyl acetate and the organics washed with brine, dried over magnesium sulfate and concentrated in vacuo. Purification of the residue by flash chomatography on silica gel (ethyl acetate:hexane, 75:25; then methylene chloride:10% ammonium hydroxide in methanol, 98:2; then 97:3; then 95:5) gave the title compound (8.0 mg). MASS: 597 (M+H).

Workup

  1. temperaturethe reaction was cooled to 0° C.
  2. stirringthe mixture stirred at low temperature
  3. customThe reaction was quenched after 45 minutes by the addition of saturated aqueous ammonium chloride and brine
  4. extractionThis was then extracted with ethyl acetate
  5. washthe organics washed with brine
  6. dry with materialdried over magnesium sulfate
  7. concentrationconcentrated in vacuo
  8. customPurification of the residue by flash chomatography on silica gel (ethyl acetate

Sources & evidence

ORD record
ord-f25de84892d1473aa845b1fcf9dfea1b
Source dataset
uspto-grants-1999_11
Patent number
US05985901

Reaction notes

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