1-Hydroxybenzotriazole → 2-(1-(cyclopropylmethyl)-5-oxo-1H-1,2,4-triazol-4(5H)-yl)-4-methyl-N-(pyridin-4-ylmethyl)thiazole-5-carboxamide

HRID 555006Notes

Reaction equation

HRID 555006 reaction equation
[CH:1]1([CH2:4][N:5]2[C:9](=[O:10])[N:8]([C:11]3[S:12][C:13]([C:17]([OH:19])=O)=[C:14]([CH3:16])[N:15]=3)[CH:7]=[N:6]2)[CH2:3][CH2:2]1.Cl.CN(C)CCCN=C=NCC.C(N(CC)C(C)C)(C)C.ON1C2C=CC=CC=2N=N1.[NH2:51][CH2:52][C:53]1[CH:58]=[CH:57][N:56]=[CH:55][CH:54]=1>CN(C)C=O.C(OCC)(=O)C>[CH:1]1([CH2:4][N:5]2[C:9](=[O:10])[N:8]([C:11]3[S:12][C:13]([C:17]([NH:51][CH2:52][C:53]4[CH:58]=[CH:57][N:56]=[CH:55][CH:54]=4)=[O:19])=[C:14]([CH3:16])[N:15]=3)[CH:7]=[N:6]2)[CH2:2][CH2:3]1

Participants

8

Reactant 5

HCID 757711-HydroxybenzotriazoleHCID 773174-PyridinemethanamineHCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 579197562-(1-(cyclopropylmethyl)-5-oxo-1H-1,2,4-triazol-4(5H)-yl)-4-methylthiazole-5-carboxylic acid

Product 1

HCID 579200152-(1-(cyclopropylmethyl)-5-oxo-1H-1,2,4-triazol-4(5H)-yl)-4-methyl-N-(pyridin-4-ylmethyl)thiazole-5-carboxamideYield 49%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 2-(1-(cyclopropylmethyl)-5-oxo-1H-1,2,4-triazol-4(5H)-yl)-4-methylthiazole-5-carboxylic acid (0.15 g, 0.53 mmol), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (0.14 g, 0.69 mmol) and N,N-diisopropylethylamine (0.09 mL, 0.69 mmol) in N,N-dimethylformamide (10 mL) was added 1-hydroxybenzotriazole (0.09 g, 0.69 mmol). The resulting mixture was stirred at ambient temperature for 15 minutes, followed by the addition of 4-aminomethylpyridine (0.07 mL, 0.69 mmol). The reaction mixture was kept stirring at ambient temperature for 20 hours, diluted with ethyl acetate (200 mL) and washed with water and brine. The organic solution was dried over anhydrous sodium sulfate and filtered. The filtrate was concentrated in vacuo and the residue was purified by column chromatography to afford the title compound in 49% yield (0.10 g): mp 169-170° C.; 1H NMR (300 MHz, CDCl3) δ 8.64-8.48 (m, 2H), 8.28-8.25 (m, 1H), 7.26-7.20 (m, 2H), 6.22 (t, J=5.8 Hz, 1H), 4.60 (d, J=5.8 Hz, 2H), 3.71 (d, J=7.2 Hz, 2H), 2.67 (s, 3H), 1.30-1.17 (m, 1H), 0.62-0.54 (m, 2H), 0.43-0.135 (m, 2H); MS (ES+) m/z 371.2 (M+1).

Workup

  1. stirringThe reaction mixture was kept stirring at ambient temperature for 20 hours
  2. washwashed with water and brine
  3. dry with materialThe organic solution was dried over anhydrous sodium sulfate
  4. filtrationfiltered
  5. concentrationThe filtrate was concentrated in vacuo
  6. customthe residue was purified by column chromatography

Sources & evidence

ORD record
ord-57000731e7c14554ba199f1b071dc9d9
Source dataset
uspto-grants-2011_11
Patent number
US08049016B2

Reaction notes

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