1H-Benzotriazole, 1-hydroxy-, ammonium salt (1:1) → HCID 178425237, compound

HRID 1526945Notes

Reaction equation

HRID 1526945 reaction equation
[CH2:1]([N:8]1[C:12]([CH3:13])=[C:11]([C:14]([OH:16])=O)[CH:10]=[N:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Cl.C(N=C=NCCCN(C)C)C.C1C=C2N=NN(O)C2=CC=1.N.[NH2:40][CH2:41][C:42]1[C:43]([OH:50])=[N:44][C:45]([CH3:49])=[CH:46][C:47]=1[CH3:48]>O.ClCCl.C(N(CC)CC)C>[CH2:1]([N:8]1[C:12]([CH3:13])=[C:11]([C:14]([NH:40][CH2:41][C:42]2[C:43]([OH:50])=[N:44][C:45]([CH3:49])=[CH:46][C:47]=2[CH3:48])=[O:16])[CH:10]=[N:9]1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

8

Reactant 4

HCID 1131751H-Benzotriazole, 1-hydroxy-, ammonium salt (1:1)HCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 64931761-benzyl-5-methyl-1H-pyrazole-4-carboxylic acidHCID 178425242HCID 178425242, compound

Product 1

HCID 178425237HCID 178425237, compoundYield 30.3%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6344DichloromethaneSolventHCID 8471TriethylamineSolvent

Conditions

Temperature
25 °C

Procedure

A mixture of 1-benzyl-5-methyl-1H-pyrazole-4-carboxylic acid (75 mg, 0.34 mmol), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (95 mg, 0.5 mmol), N-hydroxybenzotrizole (67 mg, 0.5 mmol), triethylamine (0.1 mL) and dichloromethane (5 mL) were stirred at 25° C. for 0.5 hours. Then 3-(aminomethyl)-4,6-dimethylpyridin-2-ol (50 mg, 0.33 mmol) was added. The mixture was stirred at 25° C. for 12 hours. To the mixture, water (10 ml) was added and the mixture was extracted with dichloromethane (10 mL×3). The combined organic phase was dried by sodium sulfate and then filtered. The filtrate was concentrated in vacuo. The residue was purified by column chromatography (silica gel, dichloromethane/methanol=20:1) to give 1-benzyl-N-((2-hydroxy-4,6-dimethylpyridin-3-yl)methyl)-5-methyl-1H-pyrazole-4-carboxamide as a white solid (35 mg, 29%). LRMS (M+H+) m/z: calcd 350.17; found 350. 1H NMR (300 MHz, d6-DMSO): δ 11.46 (s, 1H), 8.21 (s, 1H), 7.68 (t, J=5.1 Hz, 1H), 7.38-7.21 (m, 5H), 5.85 (s, 1H), 5.20 (s, 2H), 4.19 (d, J=5.4 Hz, 2H), 2.29 (s, 3H), 2.15 (s, 3H), 2.10 (s, 3H).

Workup

  1. stirringThe mixture was stirred at 25° C. for 12 hours
  2. extractionthe mixture was extracted with dichloromethane (10 mL×3)
  3. dry with materialThe combined organic phase was dried by sodium sulfate
  4. filtrationfiltered
  5. concentrationThe filtrate was concentrated in vacuo
  6. customThe residue was purified by column chromatography (silica gel, dichloromethane/methanol=20:1)

Sources & evidence

ORD record
ord-f2918919741f4d07bcfc1bfb7b075777
Source dataset
uspto-grants-2015_07
Patent number
US09085583B2

Reaction notes

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