Dimethylformamide → Benzyl 3-{7-bromo-3-methyl-1-[2-(3-methylureido)ethyl]-1H-indol-6-ylmethoxy}-4-{4-[3-(2-methoxybenzyloxy)propoxy]phenyl}-piperidine-1-carboxylate

HRID 1712384Notes

Reaction equation

HRID 1712384 reaction equation
[NH2:1][CH2:2][CH2:3][N:4]1[C:12]2[C:7](=[CH:8][CH:9]=[C:10]([CH2:14][O:15][CH:16]3[CH:21]([C:22]4[CH:27]=[CH:26][C:25]([O:28][CH2:29][CH2:30][CH2:31][O:32][CH2:33][C:34]5[CH:39]=[CH:38][CH:37]=[CH:36][C:35]=5[O:40][CH3:41])=[CH:24][CH:23]=4)[CH2:20][CH2:19][N:18]([C:42]([O:44][CH2:45][C:46]4[CH:51]=[CH:50][CH:49]=[CH:48][CH:47]=4)=[O:43])[CH2:17]3)[C:11]=2[Br:13])[C:6]([CH3:52])=[CH:5]1.C(N(CC)CC)C.[CH3:60][N:61](C)[CH:62]=[O:63]>>[Br:13][C:11]1[C:10]([CH2:14][O:15][CH:16]2[CH:21]([C:22]3[CH:23]=[CH:24][C:25]([O:28][CH2:29][CH2:30][CH2:31][O:32][CH2:33][C:34]4[CH:39]=[CH:38][CH:37]=[CH:36][C:35]=4[O:40][CH3:41])=[CH:26][CH:27]=3)[CH2:20][CH2:19][N:18]([C:42]([O:44][CH2:45][C:46]3[CH:51]=[CH:50][CH:49]=[CH:48][CH:47]=3)=[O:43])[CH2:17]2)=[CH:9][CH:8]=[C:7]2[C:12]=1[N:4]([CH2:3][CH2:2][NH:1][C:62]([NH:61][CH3:60])=[O:63])[CH:5]=[C:6]2[CH3:52]

Participants

4

Reactant 3

HCID 6228DimethylformamideHCID 8471TriethylamineHCID 68504218benzyl 3-[1-(2-aminoethyl)-7-bromo-3-methyl-1H-indol-6-ylmethoxy]-4-{4-[3-(2-methoxybenzyloxy)propoxy]phenyl}piperidine-1-carboxylate

Product 1

HCID 68505966Benzyl 3-{7-bromo-3-methyl-1-[2-(3-methylureido)ethyl]-1H-indol-6-ylmethoxy}-4-{4-[3-(2-methoxybenzyloxy)propoxy]phenyl}-piperidine-1-carboxylate

Procedure

The solution of 0.270 g of benzyl 3-[1-(2-aminoethyl)-7-bromo-3-methyl-1H-indol-6-ylmethoxy]-4-{4-[3-(2-methoxybenzyloxy)propoxy]phenyl}piperidine-1-carboxylate (Example 76b) in 1.5 ml of N,N-dimethylformamide is cooled to 0° C. and admixed successively with 0.066 g of N-succinimidyl N-methyl carbamate and 0.043 ml of triethylamine. The reaction mixture is stirred at room temperature over 2 hours, subsequently poured onto water (40 ml) and extracted with dichloromethane (2×40 ml). The organic phases are washed successively with water (40 ml), 1M sodium hydrogencarbonate solution (40 ml) and brine (40 ml), dried over sodium sulphate, filtered and concentrated by evaporation. The title compound is obtained as a brown oil from the residue by means of flash chromatography (SiO2 60F). Rf=0.10 (2:1 EtOAc-heptane); Rt=5.76.

Workup

  1. additionsubsequently poured onto water (40 ml)
  2. extractionextracted with dichloromethane (2×40 ml)
  3. washThe organic phases are washed successively with water (40 ml), 1M sodium hydrogencarbonate solution (40 ml) and brine (40 ml)
  4. dry with materialdried over sodium sulphate
  5. filtrationfiltered
  6. concentrationconcentrated by evaporation

Sources & evidence

ORD record
ord-5566c92d2d88470791d392c58a3c1d3f
Source dataset
uspto-grants-2010_09
Patent number
US07790715B2

Reaction notes

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