Water → HCID 23393846, compound

To a suspension of NaH (0.959 mmol, 0.038 g, 60% in mineral oil, rinsed twice with hexanes) in 5 mL of DMF at 0° C. under N2 was added a solution of 5-(2-chloro-ethoxy)-2-methyl-1H-indole-3-carboxylic acid benzyl ester (0.873 mmol, 0.300 g, Example 1, Step A) in 3.73 mL of DMF. The ice bath was removed and the solution was stirred for 2 hours at room temperature. Benzyl bromide (0.959 mmol, 0.114 mL, Aldrich) was added dropwise via syringe and the solution was stirred for 19 hours. Water (10 mL) was added and the mixture was stirred for 30 minutes. The resulting precipitate was filtered off, the filtrate was extracted with ethyl acetate (3×10 mL), and the extracts were washed with brine (1×10 mL), dried over MgSO4, and concentrated. The residue was combined with the solid and purified by silica gel flash column chromatography (10-20% ethyl acetate/hexanes) to give an off-white solid (0.236 g, 62%): 1HNMR (400 MHz, DMSO-d6) δ 2.64 (s, 3H, ArCH3),3.86-3.89 (m, 2H, CH2Cl), 4.09-4.12 (m, 2H, CH2OAr), 5.30 (s, 2H, CO2CH2Ph), 5.46 (s, 2H, NCH2Ph), 6.78 (dm, J=8.79 Hz, 1H, ArH), 6.96 (d, J=7.33 Hz, 2H, ArH), 7.18-7.30 (m, 3H, ArH), 7.32-7.40 (m, 4H, ArH), 7.44-7.49 (m, 3H, ArH); MS(APCI+): m/z 434.1 (M+1).

1. washrinsed twice with hexanes) in 5 mL of DMF at 0° C. under N2
2. customThe ice bath was removed
3. stirringthe solution was stirred for 19 hours
4. stirringthe mixture was stirred for 30 minutes
5. filtrationThe resulting precipitate was filtered off
6. extractionthe filtrate was extracted with ethyl acetate (3×10 mL)
7. washthe extracts were washed with brine (1×10 mL)
8. dry with materialdried over MgSO4
9. concentrationconcentrated
10. custompurified by silica gel flash column chromatography (10-20% ethyl acetate/hexanes)

ORD record

ord-2b1b875df9ce49d29dbf3c4b0268303f

Source dataset

uspto-grants-2005_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06951848B2