Indole-2-carboxylic acid → 1h-Indole-2-carboxylic acid {4-[4-(6-fluoro-benzo[b]thiophen-3-yl)-[1,4]diazepan-1-yl]-butyl}-amide

HRID 1986909Notes

Reaction equation

HRID 1986909 reaction equation
[NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[CH:3]=[C:2]1[C:10]([OH:12])=O.[F:13][C:14]1[CH:15]=[CH:16][C:17]2[C:21]([N:22]3[CH2:28][CH2:27][CH2:26][N:25]([CH2:29][CH2:30][CH2:31][CH2:32][NH2:33])[CH2:24][CH2:23]3)=[CH:20][S:19][C:18]=2[CH:34]=1.C(N(C(C)C)CC)(C)C.ON1C2C=CC=CC=2N=N1.O1CCN(N=C=N)CC1>CN(C=O)C>[F:13][C:14]1[CH:15]=[CH:16][C:17]2[C:21]([N:22]3[CH2:28][CH2:27][CH2:26][N:25]([CH2:29][CH2:30][CH2:31][CH2:32][NH:33][C:10]([C:2]4[NH:1][C:9]5[C:4]([CH:3]=4)=[CH:5][CH:6]=[CH:7][CH:8]=5)=[O:12])[CH2:24][CH2:23]3)=[CH:20][S:19][C:18]=2[CH:34]=1

Participants

7

Reactant 5

HCID 72899Indole-2-carboxylic acidHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 20187300MorpholinocarbodiimideHCID 577225964-[4-(6-Fluoro-benzo[b]thiophen-3-yl)-[1,4]diazapan-1-yl]butylamine

Product 1

HCID 102051101h-Indole-2-carboxylic acid {4-[4-(6-fluoro-benzo[b]thiophen-3-yl)-[1,4]diazepan-1-yl]-butyl}-amideYield 53.9%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Add indole-2-carboxylic acid (507 mg, 3.15 mmol) to a solution of 4-[4-(6-fluoro-benzo[b]thiophen-3-yl)-[1,4]diazapan-1-yl]butylamine (Example 6) (920 mg, 2.86 mmol), diisopropylethylamine (2.5 mL, 14.3 mmol), 1-hydroxy-1H-benzotriazole (503 mg, 3.72 mmol) and morpholinocarbodiimide (1.39 g, 3.29 mmol) in DMF (10 mL), and stir the solution overnight at room temperature. Remove the solvent under vacuum and dissolve the residue in EtOAc. Wash the organic phase with ether and saturated sodium chloride solution, and dry over MgSO4. Evaporate the solvent under vacuum and purify the crude product by column chromatography (EtOAc/MeOH 7:3) to obtain 716 mg of a colorless solid LC/MS, (LiChrospher 5μ, RP-18, 250 mm CH3CN/Water-gradient 20%→100% (25 min), Flow: 1.5 mL/min) tR=19.89 min, m/z=464.3.

Workup

  1. customRemove the solvent under vacuum
  2. dissolutiondissolve the residue in EtOAc
  3. washWash the organic phase with ether and saturated sodium chloride solution
  4. dry with materialdry over MgSO4
  5. customEvaporate the solvent under vacuum
  6. custompurify the crude product by column chromatography (EtOAc/MeOH 7:3)

Sources & evidence

ORD record
ord-af86d52deb984dd99065ffd4c150c93e
Source dataset
uspto-grants-2009_06
Patent number
US07550469B2

Reaction notes

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