Acetic Acid → 7-(1-Cyclopropylmethyl-piperidin-4-yloxy)-3,4-dihydro-2H-2,4a,5-triaza-fluoren-1-one

HRID 2105432Notes

Reaction equation

HRID 2105432 reaction equation
[NH:1]1[CH2:6][CH2:5][CH:4]([O:7][C:8]2[CH:20]=[C:19]3[C:11]([N:12]4[C:17](=[CH:18]3)[C:16](=[O:21])[NH:15][CH2:14][CH2:13]4)=[N:10][CH:9]=2)[CH2:3][CH2:2]1.O.[CH:23]1([CH:26]=O)[CH2:25][CH2:24]1.C(O)(=O)C.C([BH3-])#N.[Na+].C(=O)(O)[O-].[Na+]>O1CCCC1>[CH:23]1([CH2:26][N:1]2[CH2:2][CH2:3][CH:4]([O:7][C:8]3[CH:20]=[C:19]4[C:11]([N:12]5[C:17](=[CH:18]4)[C:16](=[O:21])[NH:15][CH2:14][CH2:13]5)=[N:10][CH:9]=3)[CH2:5][CH2:6]2)[CH2:25][CH2:24]1

Participants

8

Reactant 6

HCID 176Acetic AcidHCID 962WaterHCID 123114CyclopropanecarboxaldehydeHCID 516892Sodium BicarbonateHCID 5003444Sodium cyanoborohydrideHCID 684660687-(piperidin-4-yloxy)-3,4-dihydro-2H-2,4a,5-triaza-fluoren-1-one

Product 1

HCID 166791247-(1-Cyclopropylmethyl-piperidin-4-yloxy)-3,4-dihydro-2H-2,4a,5-triaza-fluoren-1-oneYield 40%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
55 °C

Procedure

To a solution of 0.40 g (1.40 mmol) 7-(piperidin-4-yloxy)-3,4-dihydro-2H-2,4a,5-triaza-fluoren-1-one in 8 mL tetrahydrofuran, 30 μL (30 μg, 1.67 mmol) water, 0.16 mL (0.15 g, 2.11 mmol) cyclopropanecarboxaldehyde, 0.24 mL (0.25 g, 4.2 mmol) acetic acid and 2.1 mL (1.93 g, 2.1 mmol) sodium cyanoborohydride (1M solution in tetrahydrofuran) were added successively and the reaction mixture was stirred for 18 hours at 55° C. After cooling to room temperature the reaction was poured on 10% aqueous sodium bicarbonate solution and was extracted three times with ethyl acetate. The combined organic layers were washed with brine, dried over magnesium sulfate, filtered and evaporated. The residue was flash-chromatographed on silica gel with dichloromethane:methanol:ammonia (9:1:0.1 v/v) as eluant to give 0.19 g (40%) of the desired compound as a white solid.

Workup

  1. temperatureAfter cooling to room temperature the reaction
  2. extractionwas extracted three times with ethyl acetate
  3. washThe combined organic layers were washed with brine
  4. dry with materialdried over magnesium sulfate
  5. filtrationfiltered
  6. customevaporated
  7. customThe residue was flash-chromatographed on silica gel with dichloromethane:methanol:ammonia (9:1:0.1 v/v) as eluant

Sources & evidence

ORD record
ord-ab3eb9f65e334c1b8f50501ad14e40f2
Source dataset
uspto-grants-2009_08
Patent number
US07579351B2

Reaction notes

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