1-Hydroxybenzotriazole → 3-amino-5-(4-fluorophenyl)-N-{2-[4-(1-pyrrolidin-1-ylethyl)phenyl]ethyl}thiophene-2-carboxamide

HRID 1668398Notes

Reaction equation

HRID 1668398 reaction equation
[NH2:1][C:2]1[CH:6]=[C:5]([C:7]2[CH:12]=[CH:11][C:10]([F:13])=[CH:9][CH:8]=2)[S:4][C:3]=1[C:14]([OH:16])=O.Cl.Cl.[N:19]1([CH:24]([C:26]2[CH:31]=[CH:30][C:29]([CH2:32][CH2:33][NH2:34])=[CH:28][CH:27]=2)[CH3:25])[CH2:23][CH2:22][CH2:21][CH2:20]1.ON1C2C=CC=CC=2N=N1.C(N(CC)C(C)C)(C)C.Cl.CN(C)CCCN=C=NCC>C(OCC)(=O)C.CN(C=O)C>[NH2:1][C:2]1[CH:6]=[C:5]([C:7]2[CH:8]=[CH:9][C:10]([F:13])=[CH:11][CH:12]=2)[S:4][C:3]=1[C:14]([NH:34][CH2:33][CH2:32][C:29]1[CH:28]=[CH:27][C:26]([CH:24]([N:19]2[CH2:23][CH2:22][CH2:21][CH2:20]2)[CH3:25])=[CH:31][CH:30]=1)=[O:16]

Participants

8

Reactant 5

HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 107523413-amino-5-(4-fluorophenyl)thiophene-2-carboxylic AcidHCID 673611332-[4-(1-Pyrrolidin-1-ylethyl)phenyl]ethanamine dihydrochloride

Product 1

HCID 673594643-amino-5-(4-fluorophenyl)-N-{2-[4-(1-pyrrolidin-1-ylethyl)phenyl]ethyl}thiophene-2-carboxamideYield 45.4%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a mixture of 3-amino-5-(4-fluorophenyl)thiophene-2-carboxylic acid (0.20 g), 2-[4-(1-pyrrolidin-1-ylethyl)phenyl]ethanamine dihydrochloride (0.22 g), 1-hydroxybenzotriazole (0.16 g), N,N-diisopropylethylamine (0.30 ml) and DMF (3.0 ml) was added 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (0.15 g), and the mixture was stirred overnight at room temperature. The reaction mixture was diluted with ethyl acetate, washed with water and saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was purified by column chromatography (hexane:ethyl acetate=9:1 (volume ratio)→1:2 (volume ratio)) using NH-silica gel to give 3-amino-5-(4-fluorophenyl)-N-{2-[4-(1-pyrrolidin-1-ylethyl)phenyl]ethyl}thiophene-2-carboxamide (0.15 g).

Workup

  1. washwashed with water and saturated brine
  2. dry with materialdried over anhydrous sodium sulfate
  3. concentrationconcentrated under reduced pressure
  4. customThe residue was purified by column chromatography (hexane

Sources & evidence

ORD record
ord-f6ac35febcb84dc6a03849c474b84cf2
Source dataset
uspto-grants-2011_08
Patent number
US07989445B2

Reaction notes

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