Potassium Carbonate → 4-[(10R,15S)-1,12-diazatetracyclo[7.6.1.05,16.010,15]hexadeca-5(16),6,8-trien-12-yl]-1-(4-fluorophenyl)butan-1-one

HRID 1292926Notes

Reaction equation

[CH:1]1[C:10]2[C@@H:11]3[CH2:16][NH:15][CH2:14][CH2:13][C@@H:12]3[N:8]3[C:9]=2[C:4]([CH2:5][CH2:6][CH2:7]3)=[CH:3][CH:2]=1.Cl[CH2:18][CH2:19][CH2:20][C:21]([C:23]1[CH:28]=[CH:27][C:26]([F:29])=[CH:25][CH:24]=1)=[O:22].C([O-])([O-])=O.[K+].[K+]>O1CCOCC1.C(Cl)(Cl)Cl>[CH:1]1[C:10]2[C@@H:11]3[CH2:16][N:15]([CH2:18][CH2:19][CH2:20][C:21]([C:23]4[CH:24]=[CH:25][C:26]([F:29])=[CH:27][CH:28]=4)=[O:22])[CH2:14][CH2:13][C@@H:12]3[N:8]3[C:9]=2[C:4]([CH2:5][CH2:6][CH2:7]3)=[CH:3][CH:2]=1

Participants

Conditions

Temperature: 100 °C

Procedure

To a solution of (7aS,11aR)-5,6,7a,8,9,10,11,11a-octahydro-4H-pyrido[3′,4′:4,5]pyrrolo[3,2,1-ij]quinoline (0.21 g, 1.0 mmol)) in 1,4-dioxane (7.0 mL) were added 4-chloro-4′-fluorobutyrophenone (0.40 g, 2.0 mmol), KI (catalytic amount) and K2CO3 (0.28 g, 2.0 mmol). The reaction mixture was heated at 100° C. for 48 h. The reaction mixture was cooled to 20° C. then diluted with CHCl3. The solution was filtered to remove excess K2CO3 and the filtrate was concentrated in vacuo and chromatographed (silica gel, CHCl3:MeOH 98:2) to give the title compound (0.22 g, 58%) as a white amorphous solid. 1H NMR (CDCl3, 300 MHz) δ 1.75-2.20 (m, 7H), 2.20-2.35 (m, 1H), 2.35-2.48 (m, 2H), 2.48-2.60 (m, 1H), 2.60-2.78 (m, 3H), 2.78-2.90 (m, 1H), 2.99 (t, J=7.2 Hz, 2H), 3.05-3.15 (m, 1H), 3.18-3.32 (m, 2H), 6.62 (t, J=7.3 Hz, 1H), 6.86 (d, J=7.3 Hz, 1H), 7.12 (t, J=8.6 Hz, 2H), 7.90-8.08 (m, 2H) ppm.

Workup

temperatureThe reaction mixture was cooled to 20° C.
filtrationThe solution was filtered
customto remove excess K2CO3
concentrationthe filtrate was concentrated in vacuo
customchromatographed (silica gel, CHCl3:MeOH 98:2)

Sources & evidence

ORD record: ord-8784ed9771e840258ccbc997d645f655
Source dataset: uspto-grants-2007_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07238690B2

Reaction notes

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