1-Hydroxybenzotriazole → HCID 71571202, compound

HRID 1500971Notes

Reaction equation

HRID 1500971 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([CH:8]=[CH:9][C:10]=1[O:11][C:12]1[CH:17]=[CH:16][CH:15]=[C:14]([C:18]2[CH:23]=[CH:22][N:21]=[N:20][CH:19]=2)[C:13]=1[C:24]#[N:25])[C:5](O)=[O:6].Cl.C(N=C=NCCCN(C)C)C.ON1C2C=CC=CC=2N=N1.[NH2:48][CH2:49][C:50]1[C:51](=[O:58])[NH:52][C:53]([CH3:57])=[CH:54][C:55]=1[CH3:56]>O.ClCCl.C(N(CC)CC)C>[Cl:1][C:2]1[CH:3]=[C:4]([CH:8]=[CH:9][C:10]=1[O:11][C:12]1[CH:17]=[CH:16][CH:15]=[C:14]([C:18]2[CH:23]=[CH:22][N:21]=[N:20][CH:19]=2)[C:13]=1[C:24]#[N:25])[C:5]([NH:48][CH2:49][C:50]1[C:51](=[O:58])[NH:52][C:53]([CH3:57])=[CH:54][C:55]=1[CH3:56])=[O:6]

Participants

8

Reactant 4

HCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 70638443-(Aminomethyl)-4,6-dimethyl-1,2-dihydropyridin-2-oneHCID 69671864HCID 69671864, compound

Product 1

HCID 71571202HCID 71571202, compoundYield 72%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6344DichloromethaneSolventHCID 8471TriethylamineSolvent

Conditions

Temperature
25 °C

Procedure

A mixture of 3-chloro-4-(2-cyano-3-(pyridazin-4-yl)phenoxy)benzoic acid (70 mg, 0.2 mmol), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (60 mg, 0.3 mmol) and N-hydroxybenzotriazole (45 mg, 0.3 mmol), triethylamine (0.1 mL) and dichloromethane (5 mL) were stirred at 25° C. for half an hour and then 3-(aminomethyl)-4,6-dimethylpyridin-2(1H)-one (30 mg, 0.2 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 3-chloro-4-(2-cyano-3-(pyridazin-4-yl)phenoxy)-N-((4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)benzamide as a white solid (70 mg, 70%).

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-cd235bea52c1474897a2ed208b063154
Source dataset
uspto-grants-2015_12
Patent number
US09206128B2

Reaction notes

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