Triethylamine → HCID 46866330, compound

HRID 1913890Notes

Reaction equation

HRID 1913890 reaction equation
Cl.[F:2][C:3]1[CH:8]=[CH:7][C:6]([N:9]2[C:18]3[C:13](=[CH:14][C:15]([O:19][CH:20]4[CH2:25][CH2:24][NH:23][CH2:22][CH2:21]4)=[CH:16][CH:17]=3)[CH2:12][CH2:11][C:10]2=[O:26])=[CH:5][CH:4]=1.C(N(CC)CC)C.C(O[C:37]1(O[Si](C)(C)C)[CH2:39][CH2:38]1)C.C([BH3-])#N.[Na+]>CO.C(O)(=O)C>[CH:37]1([N:23]2[CH2:22][CH2:21][CH:20]([O:19][C:15]3[CH:14]=[C:13]4[C:18](=[CH:17][CH:16]=3)[N:9]([C:6]3[CH:7]=[CH:8][C:3]([F:2])=[CH:4][CH:5]=3)[C:10](=[O:26])[CH2:11][CH2:12]4)[CH2:25][CH2:24]2)[CH2:39][CH2:38]1

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 2734686(1-Ethoxycyclopropoxy)trimethylsilaneHCID 5003444Sodium cyanoborohydrideHCID 66684102HCID 66684102, compound

Product 1

HCID 46866330HCID 46866330, compoundYield 37%

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 887MethanolSolvent

Procedure

A suspension of 1-(4-fluorophenyl)-6-(piperidin-4-yloxy)-3,4-dihydroquinolin-2(1H)-one hydrochloride prepared in Example 7-(3) (0.30 g), triethylamine (0.080 g), [(1-ethoxycyclopropyl)-oxy]trimethylsilane (0.69 g), acetic acid (0.48 g) and molecular sieves 3A (1.0 g) in methanol (10 mL) was stirred at room temperature for 1 hour, followed by addition of sodium cyanoborohydride (0.25 g) and stirring at the same temperature for 16 hours. The reaction mixture was warmed to 95° C., heated under reflux for 7 hours, and then cooled to room temperature, followed by filtration to remove insoluble materials. The filtrate was concentrated under reduced pressure, and the resulting residue was purified by silica gel column chromatography (eluting solvent: chloroform→chloroform/methanol=4/1) and preparative TLC (on a single plate of 2 mm thickness, developing solvent: chloroform/methanol=9/1) to give the titled compound (0.11 g, 37%) as a colorless amorphous substance.

Workup

  1. stirringstirring at the same temperature for 16 hours
  2. temperatureThe reaction mixture was warmed to 95° C.
  3. temperatureheated
  4. temperatureunder reflux for 7 hours
  5. temperaturecooled to room temperature
  6. filtrationfollowed by filtration
  7. customto remove insoluble materials
  8. concentrationThe filtrate was concentrated under reduced pressure
  9. customthe resulting residue was purified by silica gel column chromatography (eluting solvent: chloroform→chloroform/methanol=4/1) and preparative TLC (on a single plate of 2 mm thickness

Sources & evidence

ORD record
ord-a515ccbcb1b6449e8879263c47858227
Source dataset
uspto-grants-2013_12
Patent number
US08609847B2

Reaction notes

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