1-Hydroxybenzotriazole → 4-(4-bromophenyl)-5-({(3S)-1-[(1-methylcyclopropyl)carbonyl]-3-pyrrolidinyl}methyl)-2,4-dihydro-3H-1,2,4-triazol-3-one

HRID 525246Notes

Reaction equation

HRID 525246 reaction equation
Cl.[Br:2][C:3]1[CH:8]=[CH:7][C:6]([N:9]2[C:13]([CH2:14][C@@H:15]3[CH2:19][CH2:18][NH:17][CH2:16]3)=[N:12][NH:11][C:10]2=[O:20])=[CH:5][CH:4]=1.[CH3:21][C:22]1([C:25](O)=[O:26])[CH2:24][CH2:23]1.Cl.CN(C)CCCN=C=NCC.ON1C2C=CC=CC=2N=N1.C(N(CC)C(C)C)(C)C>CN(C)C=O>[Br:2][C:3]1[CH:8]=[CH:7][C:6]([N:9]2[C:13]([CH2:14][C@@H:15]3[CH2:19][CH2:18][N:17]([C:25]([C:22]4([CH3:21])[CH2:24][CH2:23]4)=[O:26])[CH2:16]3)=[N:12][NH:11][C:10]2=[O:20])=[CH:5][CH:4]=1

Participants

7

Reactant 5

HCID 757711-HydroxybenzotriazoleHCID 813261-Methylcyclopropanecarboxylic acidHCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 673774324-(4-bromophenyl)-5-[(3S)-3-pyrrolidinylmethyl]-2,4-dihydro-3H-1,2,4-triazol-3-one Hydrochloride

Product 1

HCID 673763504-(4-bromophenyl)-5-({(3S)-1-[(1-methylcyclopropyl)carbonyl]-3-pyrrolidinyl}methyl)-2,4-dihydro-3H-1,2,4-triazol-3-oneYield 87%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Into a 5 mL microwave vial was placed 4-(4-bromophenyl)-5-[(3S)-3-pyrrolidinylmethyl]-2,4-dihydro-3H-1,2,4-triazol-3-one hydrochloride (0.473 mmol), 1-methylcyclopropanecarboxylic acid (0.499 mmol), N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (1.200 mmol), 1-hydroxybenzotriazole (1.208 mmol), N,N-diisopropylethylamine (1.431 mmol), and N,N-dimethylformamide (2 mL). The vial was capped and the contents were stirred at room temperature for 4 h. Purification of the crude material by reverse phase HPLC (10-40% acetonitrile w/0.1% TFA/water w/0.1% TFA) followed by collection and concentration of the desired fractions provided the title compound (166 mg, 87%). MS(ES)+ m/e 405.0, 407.1 [M+H]+.

Workup

  1. customThe vial was capped
  2. customPurification of the crude material by reverse phase HPLC (10-40% acetonitrile w/0.1% TFA/water w/0.1% TFA)
  3. customfollowed by collection and concentration of the desired fractions

Sources & evidence

ORD record
ord-6aab7034cd964cd296f3b537ae6f3dd4
Source dataset
uspto-grants-2016_05
Patent number
US09340529B2

Reaction notes

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