1,2-Dimethoxyethane → 9-tert-butyl-2-(3-pyridyl)-14-bromo-3-methoxy-5,6,10,11,12,13-hexahydroazocino[4',3':4,5]pyrrolo[2,1-a]isoquinolin-8(9H)-one

HRID 1971755Notes

Reaction equation

[C:1]([N:5]1[CH2:27][CH2:26][CH2:25][CH2:24][C:8]2[C:9]([Br:23])=[C:10]3[C:19]4[CH:18]=[C:17](Br)[C:16]([O:21][CH3:22])=[CH:15][C:14]=4[CH2:13][CH2:12][N:11]3[C:7]=2[C:6]1=[O:28])([CH3:4])([CH3:3])[CH3:2].[N:29]1[CH:34]=[CH:33][CH:32]=[C:31](B(O)O)[CH:30]=1.C([O-])([O-])=O.[K+].[K+].COCCOC>O>[C:1]([N:5]1[CH2:27][CH2:26][CH2:25][CH2:24][C:8]2[C:9]([Br:23])=[C:10]3[C:19]4[CH:18]=[C:17]([C:31]5[CH:30]=[N:29][CH:34]=[CH:33][CH:32]=5)[C:16]([O:21][CH3:22])=[CH:15][C:14]=4[CH2:13][CH2:12][N:11]3[C:7]=2[C:6]1=[O:28])([CH3:2])([CH3:3])[CH3:4]

Participants

Conditions

Temperature: 90 °C

Procedure

A mixture of 250 mg of 25a, 72 mg of pyridine-3-boronic acid, 135 mg of K2CO3 and 5 ml of degassed 90% aqueous DME was heated under N2 for 16 h at 90° C. The reaction was then cooled and diluted with water, and the product was extracted with ethyl acetate. The organic extract was washed with water, dried and concentrated, and the remainder was chromatographed over silica gel (using a gradient of heptane/ethyl acetate as eluent). The product isolated was triturated with diethylether, to provide 183 mg of 25b; NMR (CDCl3) δ 8.85, 8.56, 7.91, and 7.35 (4×m, 4, pyridyl-H), 8.37 and 6.87 (2×s, 2, Ar—H), 4.45 and 3.40-3.90 (br.m, 4, 2×CH2), 3.05 (bm, 2, CH2), 2.60 (br.m, 2, CH2), 1.90 and 1.70 (2×br.m, 4, 2×CH2), 1.58 (s, 9, tertC4H9).

Workup

temperatureThe reaction was then cooled
extractionthe product was extracted with ethyl acetate
extractionThe organic extract
washwas washed with water
customdried
concentrationconcentrated
customthe remainder was chromatographed over silica gel (
customThe product isolated
customwas triturated with diethylether

Sources & evidence

ORD record: ord-4a2332bb47384baba475b9f9d91e2831
Source dataset: uspto-grants-2013_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08431564B2

Reaction notes

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