Sodium triacetoxyborohydride → HCID 15983188, compound

HRID 1644284Notes

Reaction equation

HRID 1644284 reaction equation
[NH2:1][CH:2]1[CH2:7][CH2:6][N:5]([CH2:8][CH2:9][N:10]2[C:19]3[C:14](=[CH:15][CH:16]=[C:17]([O:20][CH3:21])[CH:18]=3)[C:13](=[O:22])[CH:12]=[CH:11]2)[CH2:4][CH2:3]1.[O:23]1[C:32]2[CH:31]=[C:30]([CH:33]=O)[N:29]=[CH:28][C:27]=2[O:26][CH2:25][CH2:24]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>C(Cl)(Cl)Cl.CO>[O:23]1[C:32]2[CH:31]=[C:30]([CH2:33][NH:1][CH:2]3[CH2:7][CH2:6][N:5]([CH2:8][CH2:9][N:10]4[C:19]5[C:14](=[CH:15][CH:16]=[C:17]([O:20][CH3:21])[CH:18]=5)[C:13](=[O:22])[CH:12]=[CH:11]4)[CH2:4][CH2:3]3)[N:29]=[CH:28][C:27]=2[O:26][CH2:25][CH2:24]1

Participants

5

Reactant 3

HCID 5049666Sodium triacetoxyborohydrideHCID 218736682,3-Dihydro[1,4]dioxino[2,3-c]pyridine-7-carbaldehydeHCID 66774065HCID 66774065, compound2×

Product 1

HCID 15983188HCID 15983188, compound

Reagents, catalysts & solvents 1

HCID 21584188Chloroform methanolSolvent

Conditions

Temperature
0 °C

Procedure

A solution of 1-[2-(4-aminopiperidin-1-yl)ethyl]-7-methoxyquinolin-4(1H)-one (Intermediate 8, 60 mg, 0.20 mmol) and 2,3-dihydro[1,4]dioxino[2,3-c]pyridine-7-carbaldehyde (WO 2004/058144) (33 mg, 0.20 mmol) in dry chloroform/methanol (5 mL, 1:1) was heated over 3 Å molecular sieves at 70° C. for 3 hours. The reaction mixture was cooled to 0° C., and sodium triacetoxyborohydride (127 mg, 0.6 mmol) was added and the resulting mixture was stirred at room temperature for 30 minutes. The mixture was then filtered through a 0.45 μm membrane, acidified with conc. HCl to pH 1 and concentrated to dryness under reduced pressure. The residue was taken up in dichloromethane (50 mL) and saturated aqueous sodium hydrogen carbonate solution (5 mL). The pH of the aqueous phase was adjusted to pH10 with 1M aqueous sodium hydroxide solution. The aqueous phase was back extracted twice with dichloromethane (2×20 mL) and the combined organic phases were dried over sodium sulfate. Chromatography on silica gel with dichloromethane/methanol (4:1), containing 0.125% ammonium hydroxide, gave the free base of the title compound as a colorless oil. The free base was taken up in dichloromethane (2 mL), ethanol (7 mL) was added, followed by addition of 1M HCl in ether (0.45 mL). The colorless precipitate was collected by filtration and gave 84 mg (81% yield) of the bis-hydrochloride salt of the product, mp 260° C.

Workup

  1. filtrationThe mixture was then filtered through a 0.45 μm membrane
  2. concentrationconcentrated to dryness under reduced pressure
  3. extractionThe aqueous phase was back extracted twice with dichloromethane (2×20 mL)
  4. dry with materialthe combined organic phases were dried over sodium sulfate
  5. additionChromatography on silica gel with dichloromethane/methanol (4:1), containing 0.125% ammonium hydroxide

Sources & evidence

ORD record
ord-eb0c3fa5605f4563bc1574809c6f65aa
Source dataset
uspto-grants-2012_02
Patent number
US08124602B2

Reaction notes

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