Tributylphosphine → 8-(1-isopropylpiperidin-4-yloxy)-3,4-dihydropyrazino[1,2-a]indol-1(2H)-one

HRID 506638Notes

Reaction equation

[OH:1][C:2]1[CH:10]=[CH:9][C:8]2[N:7]3[CH2:11][CH2:12][NH:13][C:14](=[O:15])[C:6]3=[CH:5][C:4]=2[CH:3]=1.[CH:16]([N:19]1[CH2:24][CH2:23][CH:22](O)[CH2:21][CH2:20]1)([CH3:18])[CH3:17].C(P(CCCC)CCCC)CCC.N(C(N1CCCCC1)=O)=NC(N1CCCCC1)=O>O1CCCC1>[CH:16]([N:19]1[CH2:24][CH2:23][CH:22]([O:1][C:2]2[CH:10]=[CH:9][C:8]3[N:7]4[CH2:11][CH2:12][NH:13][C:14](=[O:15])[C:6]4=[CH:5][C:4]=3[CH:3]=2)[CH2:21][CH2:20]1)([CH3:18])[CH3:17]

Participants

Conditions

Temperature: 0 °C

Procedure

To the suspension of 1.0 g (4.9 mmol) 8-hydroxy-3,4-dihydro-2H-pyrazino[1,2-a]indol-1-one in 70 ml tetrahydrofuran, a solution of 0.92 g (0.64 mmol) 1-isopropyl-piperidin-4-ol (commercially available) in 25 mL tetrahydrofuran, and 2.4 mL (2.0 g, 9.9 mmol) tributylphosphine were added. Another 20 mL tetrahydrofuran was added, and then the suspension was cooled to 0° C. Within 60 min., 2.5 g (9.9 mmol) 1,1′-(azodicarbonyl)dipiperidine was added under stirring and the reaction was allowed to reach room temperature. After 16 hours the suspension was filtered and the filtrate was evaporated. The residue was flash-chromatographed two times on silica gel with dichloromethane:methanol:ammonia (9:1:0.1 v/v) to give 0.43 g (26%) of the product as a light brown solid.

Workup

customto reach room temperature
filtrationAfter 16 hours the suspension was filtered
customthe filtrate was evaporated
customThe residue was flash-chromatographed two times on silica gel with dichloromethane:methanol:ammonia (9:1:0.1 v/v)

Sources & evidence

ORD record: ord-59b37a41cd884e0bad5c1277b4ea0c0e
Source dataset: uspto-grants-2010_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07786109B2

Reaction notes

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