Sodium triacetoxyborohydride → HCID 15983189, compound

HRID 1644288Notes

Reaction equation

HRID 1644288 reaction equation
[NH2:1][CH:2]1[CH2:7][CH2:6][N:5]([CH2:8][CH2:9][N:10]2[C:18]3[C:13](=[CH:14][CH:15]=[C:16]([O:19][CH3:20])[CH:17]=3)[CH:12]=[C:11]2[C:21]([O:23][CH3:24])=[O:22])[CH2:4][CH2:3]1.[O:25]1[C:34]2[CH:33]=[C:32]([CH:35]=O)[N:31]=[CH:30][C:29]=2[O:28][CH2:27][CH2:26]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>C(Cl)(Cl)Cl.CO>[O:25]1[C:34]2[CH:33]=[C:32]([CH2:35][NH:1][CH:2]3[CH2:3][CH2:4][N:5]([CH2:8][CH2:9][N:10]4[C:18]5[C:13](=[CH:14][CH:15]=[C:16]([O:19][CH3:20])[CH:17]=5)[CH:12]=[C:11]4[C:21]([O:23][CH3:24])=[O:22])[CH2:6][CH2:7]3)[N:31]=[CH:30][C:29]=2[O:28][CH2:27][CH2:26]1

Participants

5

Reactant 3

HCID 5049666Sodium triacetoxyborohydrideHCID 218736682,3-Dihydro[1,4]dioxino[2,3-c]pyridine-7-carbaldehydeHCID 66774305HCID 66774305, compound2×

Product 1

HCID 15983189HCID 15983189, compoundYield 82%

Reagents, catalysts & solvents 1

HCID 21584188Chloroform methanolSolvent

Conditions

Temperature
0 °C

Procedure

A solution of methyl 1-[2-(4-aminopiperidin-1-yl)ethyl]-6-methoxy-1H-indole-2-carboxylate (Intermediate 12, 200 mg, 0.60 mmol) and 2,3-dihydro[1,4]dioxino[2,3-c]pyridine-7-carbaldehyde (WO 2004/058144) (100 mg, 0.60 mmol) in dry chloroform/methanol (10 mL, 1:1) was heated over 3 Å molecular sieves at 70° C. for 3 hours. The reaction mixture was cooled to 0° C., sodium triacetoxy borohydride (384 mg, 1.8 mmol) was added and the resulting mixture was stirred at room temperature for 30 minutes. The reaction mixture was filtered through a 0.45 μm membrane and concentrated to dryness under reduced pressure. The residue was taken up in dichloromethane (150 mL) and saturated aqueous sodium hydrogen carbonate solution (30 mL), the aqueous phase back extracted once with dichloromethane (70 mL) and the combined organic phases were dried over sodium sulfate. Chromatography on silica gel with dichloromethane/methanol (5:1), containing 0.125% ammonium hydroxide, gave the free base of the title compound, 239 mg (82% yield), as a colorless solid, mp 130° C.

Workup

  1. filtrationThe reaction mixture was filtered through a 0.45 μm membrane
  2. concentrationconcentrated to dryness under reduced pressure
  3. extractionsaturated aqueous sodium hydrogen carbonate solution (30 mL), the aqueous phase back extracted once with dichloromethane (70 mL)
  4. dry with materialthe combined organic phases were dried over sodium sulfate
  5. additionChromatography on silica gel with dichloromethane/methanol (5:1), containing 0.125% ammonium hydroxide

Sources & evidence

ORD record
ord-a21633d853c649e59cd64176bb1e95c3
Source dataset
uspto-grants-2012_02
Patent number
US08124602B2

Reaction notes

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