Dimethylformamide → 4-{[(4-amino-2-ethylthiazolo[4,5-c]quinolin-7-yl)oxy]methyl}-N-[2-(1H-indol-2-yl)ethyl]benzenesulfonamide

HRID 913367Notes

Reaction equation

[NH2:1][C:2]1[C:11]2[N:12]=[C:13]([CH2:15][CH3:16])[S:14][C:10]=2[C:9]2[CH:8]=[CH:7][C:6]([OH:17])=[CH:5][C:4]=2[N:3]=1.C(=O)([O-])[O-].[Cs+].[Cs+].[CH3:24][N:25]([CH:27]=O)C.Br[CH2:30][C:31]1[CH:36]=[CH:35][C:34]([S:37]([NH:40][CH2:41][CH2:42]C2C3C(=CC=CC=3)NC=2)(=[O:39])=[O:38])=[CH:33][CH:32]=1>O>[NH2:1][C:2]1[C:11]2[N:12]=[C:13]([CH2:15][CH3:16])[S:14][C:10]=2[C:9]2[CH:8]=[CH:7][C:6]([O:17][CH2:30][C:31]3[CH:36]=[CH:35][C:34]([S:37]([NH:40][CH2:41][CH2:42][C:24]4[NH:25][C:27]5[C:8]([CH:7]=4)=[CH:9][CH:4]=[CH:5][CH:6]=5)(=[O:39])=[O:38])=[CH:33][CH:32]=3)=[CH:5][C:4]=2[N:3]=1

Participants

Conditions

Temperature: 75 °C

Procedure

A mixture of 4-amino-2-ethylthiazolo[4,5-c]quinolin-7-ol (245 mg, 1.0 mmol), cesium carbonate (1.3 g, 4.0 mmol), and DMF (20 mL) was stirred at 75° C. for 10 minutes. {[4-(Bromomethyl)phenyl]sulfonyl}[2-(indol-3-yl)ethyl]amine (432 mg, 1.1 mmol) was added in portions over a period of 30 minutes. Several small additions of {[4-(bromomethyl)phenyl]sulfonyl}[2-(indol-3-yl)ethyl]amine were made over several hours. The reaction mixture was diluted with water (250 mL) and then extracted with chloroform (3×100 mL). The extracts were combined and concentrated under reduced pressure. The residue was purified by HPFC eluting with a gradient of 0-20% CMA in chloroform over 700 mL and then with 20% CMA in chloroform over 400 mL. The resulting solid was recrystallized from 100:1 acetonitrile:water to provide 6 mg of 4-{[(4-amino-2-ethylthiazolo[4,5-c]quinolin-7-yl)oxy]methyl}-N-[2-(1H-indol-2-yl)ethyl]benzenesulfonamide as an off-white solid, mp 100.0-101.0° C. MS (APCI) m/z 558 (M+H)+; Anal. calcd for C29H27N5O3S2: C, 62.46; H, 4.88; N, 12.56. Found C, 62.27; H, 4.63; N, 12.73.

Workup

extractionextracted with chloroform (3×100 mL)
concentrationconcentrated under reduced pressure
customThe residue was purified by HPFC
washeluting with a gradient of 0-20% CMA in chloroform over 700 mL
customThe resulting solid was recrystallized from 100:1 acetonitrile

Sources & evidence

ORD record: ord-8fe5b62b94604003a94ae7366be4dc9c
Source dataset: uspto-grants-2011_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08026366B2

Reaction notes

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