1-Hydroxybenzotriazole → 1H-Indole-5-carboxylic acid {2-oxo-2-[4-(2-trifluoromethyl-benzoyl)-piperazine-1-yl]-ethyl}-amide

HRID 1178072Notes

Reaction equation

HRID 1178072 reaction equation
CCN(C(C)C)C(C)C.[NH:10]1[C:18]2[C:13](=[CH:14][C:15]([C:19]([NH:21][CH2:22][C:23]([OH:25])=O)=[O:20])=[CH:16][CH:17]=2)[CH:12]=[CH:11]1.C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.Cl.Cl.[N:49]1([C:55]([C:57]2[CH:62]=[CH:61][CH:60]=[CH:59][C:58]=2[C:63]([F:66])([F:65])[F:64])=[O:56])[CH2:54][CH2:53][NH:52][CH2:51][CH2:50]1>CN(C=O)C.O>[O:25]=[C:23]([N:52]1[CH2:53][CH2:54][N:49]([C:55](=[O:56])[C:57]2[CH:62]=[CH:61][CH:60]=[CH:59][C:58]=2[C:63]([F:66])([F:64])[F:65])[CH2:50][CH2:51]1)[CH2:22][NH:21][C:19]([C:15]1[CH:14]=[C:13]2[C:18](=[CH:17][CH:16]=1)[NH:10][CH:11]=[CH:12]2)=[O:20]

Participants

8

Reactant 5

HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 4908648[(1H-Indole-5-carbonyl)-amino]-acetic acidHCID 167337831-(2-Trifluoromethylbenzoyl)piperazine hydrochloride

Product 1

HCID 595596591H-Indole-5-carboxylic acid {2-oxo-2-[4-(2-trifluoromethyl-benzoyl)-piperazine-1-yl]-ethyl}-amideYield 45%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

DIPEA (0.111 mL, 0.64 mmol) was added to a stirred solution of [(1H-Indole-5-carbonyl)-amino]-acetic acid (40 mg, 0.18 mmol) in DMF (1.0 mL). HOBT (29 mg, 0.22 mmol) and EDCI.HCl (42 mg, 0.22 mmol) were added, followed by the addition of piperazine-1-yl-(2-trifluoromethyl-phenyl)-methanone hydrochloride (59 mg, 0.20 mmol) at room temperature. The resulting mixture was stirred at room temperature overnight. The mixture was then diluted with water and the resulting precipitate was filtered to afford 1H-Indole-5-carboxylic acid {2-oxo-2-[4-(2-trifluoromethyl-benzoyl)-piperazine-1-yl]-ethyl}-amide in 45% yield. LC-MS purity: 91%, 1H NMR (CDCl3): δ 8.48 (s, 1H), 8.18 (s, 1H), 7.78-7.54 (m, 4H), 7.42-7.30 (m, 2H), 7.28 (s, 1H), 6.62 (s, 1H), 4.40-4.20 (m, 2H), 4.18-3.82 (m, 2H), 3.78-3.52 (m, 4H), 3.24 (s, 2H).

Workup

  1. filtrationthe resulting precipitate was filtered

Sources & evidence

ORD record
ord-23a33f6afbf443eab2cec1c9d8274c3b
Source dataset
uspto-grants-2010_11
Patent number
US07842696B2

Reaction notes

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