O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate → 5-Fluoro-1-methyl-3-[(4-{4-[3-(2-methylpiperidin-1-yl)propoxy]phenyl}piperazin-1-yl)carbonyl]-1H-indole

HRID 1434590

Reaction equation

HRID 1434590 reaction equation
[F:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[N:7]([CH3:11])[CH:6]=[C:5]2[C:12]([OH:14])=O.F[B-](F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2C=CC=CC=2N=N1.[CH3:37][CH:38]1[CH2:43][CH2:42][CH2:41][CH2:40][N:39]1[CH2:44][CH2:45][CH2:46][O:47][C:48]1[CH:53]=[CH:52][C:51]([N:54]2[CH2:59][CH2:58][NH:57][CH2:56][CH2:55]2)=[CH:50][CH:49]=1>CN(C=O)C.C(N(C(C)C)CC)(C)C>[F:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[N:7]([CH3:11])[CH:6]=[C:5]2[C:12]([N:57]1[CH2:58][CH2:59][N:54]([C:51]2[CH:50]=[CH:49][C:48]([O:47][CH2:46][CH2:45][CH2:44][N:39]3[CH2:40][CH2:41][CH2:42][CH2:43][CH:38]3[CH3:37])=[CH:53][CH:52]=2)[CH2:55][CH2:56]1)=[O:14]

Participants

6

Reactant 3

HCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 183851025-fluoro-1-methyl-1H-indole-3-carboxylic acidHCID 579358411-{4-[3-(2-Methylpiperidin-1-yl)propoxy]phenyl}piperazine

Product 1

HCID 579357735-Fluoro-1-methyl-3-[(4-{4-[3-(2-methylpiperidin-1-yl)propoxy]phenyl}piperazin-1-yl)carbonyl]-1H-indoleYield 45.4%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolvent2×HCID 81531DiisopropylethylamineSolvent

Procedure

A solution of 5-fluoro-1-methyl-1H-indole-3-carboxylic acid (19.3 mg) and O-(1H-benzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium tetrafluoroborate (TBTU) (56 mg) in DMF (1 ml) and diisopropylethylamine (0.035 ml) was stirred for 10 min before 1-{4-[3-(2-methylpiperidin-1-yl)propoxy]phenyl}piperazine (E76b) (21.3 mg) in DMF (0.5 ml) was added. The mixture was stirred for 18 h and then concentrated under reduced pressure. The residue was purified by SPE ion exchange chromatography on an SCX-2 cartridge (1 g). The cartridge was washed with methanol (3 ml) and the product eluted with 2M ammonia in methanol (2.5 ml), to give the title compound (15 mg) LCMS RT=2.42 min, ES+ve m/z 493 (M+H)+.

Workup

  1. additionwas added
  2. concentrationconcentrated under reduced pressure
  3. customThe residue was purified by SPE ion exchange chromatography on an SCX-2 cartridge (1 g)
  4. washThe cartridge was washed with methanol (3 ml)
  5. washthe product eluted with 2M ammonia in methanol (2.5 ml)

Sources & evidence

ORD record
ord-7338ca25405f4cc3ae8e178f4bc53e3d
Source dataset
uspto-grants-2009_11
Patent number
US07615550B2

Linked notes

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