Sodium triacetoxyborohydride → 1-(2-{4-[(2,3-Dihydro[1,4]dioxino[2,3-c]pyridin-7-ylmethyl)amino]piperidin-1-yl}ethyl)-7-fluoroquinoxalin-2(1H)-one

HRID 255305Notes

Reaction equation

HRID 255305 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]([F:20])[CH:18]=3)[N:13]=[CH:12][C:11]2=[O:21])[CH2:4][CH2:3]1.[O:22]1[C:31]2[CH:30]=[C:29]([CH:32]=O)[N:28]=[CH:27][C:26]=2[O:25][CH2:24][CH2:23]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>CO.C(Cl)(Cl)Cl>[O:22]1[C:31]2[CH:30]=[C:29]([CH2:32][NH:1][CH:2]3[CH2:3][CH2:4][N:5]([CH2:8][CH2:9][N:10]4[C:19]5[C:14](=[CH:15][CH:16]=[C:17]([F:20])[CH:18]=5)[N:13]=[CH:12][C:11]4=[O:21])[CH2:6][CH2:7]3)[N:28]=[CH:27][C:26]=2[O:25][CH2:24][CH2:23]1

Participants

5

Reactant 3

HCID 5049666Sodium triacetoxyborohydrideHCID 218736682,3-Dihydro[1,4]dioxino[2,3-c]pyridine-7-carbaldehydeHCID 593979071-(2-(4-aminopiperidin-1-yl)ethyl)-7-fluoroquinoxalin-2(1H)-one2×

Product 1

HCID 159824081-(2-{4-[(2,3-Dihydro[1,4]dioxino[2,3-c]pyridin-7-ylmethyl)amino]piperidin-1-yl}ethyl)-7-fluoroquinoxalin-2(1H)-oneYield 54.9%

Reagents, catalysts & solvents 1

HCID 21584188Chloroform methanolSolvent

Conditions

Temperature
70 °C

Procedure

A mixture of 1-[2-(4-aminopiperidin-1-yl)ethyl]-7-fluoroquinoxalin-2(1H)-one (Intermediate 140, 85 mg, 0.29 mmol), 2,3-dihydro[1,4]dioxino[2,3-c]pyridine-7-carbaldehyde (WO 2004/058144) (49 mg, 0.29 mmol) and molecular sieves 3 Å in dry methanol/chloroform (1:1, 10 mL) was heated to 70° C. for 3 hours. The reaction was allowed to cool to room temperature and sodium triacetoxy borohydride (190 mg, 0.88 mmol) was added. After 30 minutes, the reaction was filtered through celite, the filtrate was concentrated to dryness, taken up in 15% methanol/chloroform, and washed with saturated sodium bicarbonate solution. The aqueous phase was reextracted twice with 15% methanol/chloroform. The combined organic phases were dried over magnesium sulfate, filtered, and concentrated to dryness. Chromatography on silica gel with 5% methanol in dichloromethane containing 0.25% ammonium hydroxide gave 70 mg (54%) of the title compound as an off-white solid.

Workup

  1. temperatureto cool to room temperature
  2. filtrationthe reaction was filtered through celite
  3. concentrationthe filtrate was concentrated to dryness
  4. washwashed with saturated sodium bicarbonate solution
  5. dry with materialThe combined organic phases were dried over magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated to dryness

Sources & evidence

ORD record
ord-f84b94a003544496bad2f530ea712fca
Source dataset
uspto-grants-2011_01
Patent number
US07875715B2

Reaction notes

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