Dimethylformamide → 1H-Indolamine
Reaction equation
C(OC([C:11]1[C:19]2[C:14](=[CH:15][CH:16]=[C:17](CCOS(C)(=O)=O)[CH:18]=2)[NH:13][C:12]=1C)=O)C1C=CC=CC=1.C([O-])([O-])=O.[K+].[K+].C[N:35](C=O)C>>[NH:13]1[C:14]2[C:19](=[CH:18][CH:17]=[CH:16][CH:15]=2)[CH:11]=[C:12]1[NH2:35]Participants
Conditions
- Temperature
- 80 °C
Procedure
5-(2-Methanesulfonyloxy-ethyl)-2-methyl-1H-indole-3-carboxylic acid benzyl ester (0.300 g, 0.770 mmol, 1 eq, Example 56, Step D) was suspended in DMF (5 mL) under Ar. K2CO3 (0.425 g, 3.080 mmol, 4 eq) was added followed by the addition of (1S,4S)-(+)-1-Aza-5-oxabicycle[2,2,1]-heptane hydrochloride (0.314 g, 2.320 mmol, 3 eq). The reaction mixture was stirred at 80° C. for 18 hours. Then the reaction was quenched with saturated sodium bicarbonate and extracted with ethyl acetate (3×). The combined organic phases were washed with brine and dried over Na2SO4. After removing the solvent, the residue was loaded on silica gel and chromatographed, eluting with ethyl acetate/methanol/triethyl amine (100/10/1). 0.150 g (50%) of the indole-amine was obtained as a white solid. This was converted to the .HCl salt. LC/MS (ESI+) 391 (M+1); Anal. Calcd for C24H26N2O3.1HCl.0.90H2O: C, 65.05; H, 6.55; N, 6.32; Found: C, 65.05; H, 6.60; N, 6.13.
Workup
- customThen the reaction was quenched with saturated sodium bicarbonate
- extractionextracted with ethyl acetate (3×)
- washThe combined organic phases were washed with brine
- dry with materialdried over Na2SO4
- customAfter removing the solvent
- customchromatographed
- washeluting with ethyl acetate/methanol/triethyl amine (100/10/1)
Sources & evidence
- ORD record
- ord-3ddddb11997d454ab424423b5caf9ff8
- Source dataset
- uspto-grants-2005_10
- Patent number
- US06951848B2
Reaction notes
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