Acetic Acid → 8-(1-(cyclopropylmethyl)piperidin-4-yloxy)-3,4-dihydropyrazino[1,2-a]indol-1(2H)-one

HRID 506644Notes

Reaction equation

[NH:1]1[CH2:6][CH2:5][CH:4]([O:7][C:8]2[CH:16]=[CH:15][C:14]3[N:13]4[CH2:17][CH2:18][NH:19][C:20](=[O:21])[C:12]4=[CH:11][C:10]=3[CH:9]=2)[CH2:3][CH2:2]1.[CH:22]1([CH:25]=O)[CH2:24][CH2:23]1.C(O)(=O)C.C([BH3-])#N.[Na+].C(=O)(O)[O-].[Na+]>O1CCCC1.O>[CH:22]1([CH2:25][N:1]2[CH2:2][CH2:3][CH:4]([O:7][C:8]3[CH:16]=[CH:15][C:14]4[N:13]5[CH2:17][CH2:18][NH:19][C:20](=[O:21])[C:12]5=[CH:11][C:10]=4[CH:9]=3)[CH2:5][CH2:6]2)[CH2:24][CH2:23]1

Participants

Conditions

Temperature: 55 °C

Procedure

To the solution of 0.27 g (0.95 mmol) 8-(piperidin-4-yloxy)-3,4-dihydro-2H-pyrazino[1,2-a]indol-1-one in 6 mL tetrahydrofuran, 20 μL water, 11 μL (99 μg, 1.42 mmol) cyclopropanecarboxaldehyde, 0.16 mL (0.17 g, 2.8 mmol) acetic acid and 1.42 mL (1.42 mmol, 1M solution in tetrahydrofuran) sodium cyanoborohydride were added and the reaction mixture was stirred for 18 hours at 55° C. The mixture was poured on 10% aqueous sodium bicarbonate 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 96 μg (30%) of the desired compound as a white solid.

Workup

extractionwas extracted three times with ethyl acetate
washThe combined organic layers were washed with brine
dry with materialdried over magnesium sulfate
filtrationfiltered
customevaporated
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-1f92fa6bbe804a9c918f00bda966e38f
Source dataset: uspto-grants-2010_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07786109B2

Reaction notes

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