1-Hydroxybenzotriazole → HCID 178425208, compound

HRID 1500996Notes

Reaction equation

HRID 1500996 reaction equation
[O:1]([C:8]1[CH:9]=[CH:10][C:11]([C:14]([OH:16])=O)=[N:12][CH:13]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Cl.C(N=C=NCCCN(C)C)C.ON1C2C=CC=CC=2N=N1.[NH2:39][CH2:40][C:41]1[C:42]([OH:49])=[N:43][C:44]([CH3:48])=[CH:45][C:46]=1[CH3:47]>O.ClCCl.C(N(CC)CC)C>[OH:49][C:42]1[C:41]([CH2:40][NH:39][C:14](=[O:16])[C:11]2[CH:10]=[CH:9][C:8]([O:1][C:2]3[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=3)=[CH:13][N:12]=2)=[C:46]([CH3:47])[CH:45]=[C:44]([CH3:48])[N:43]=1

Participants

8

Reactant 4

HCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 222614835-Phenoxypyridine-2-carboxylic acidHCID 178425242HCID 178425242, compound

Product 1

HCID 178425208HCID 178425208, compoundYield 37%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6344DichloromethaneSolventHCID 8471TriethylamineSolvent

Conditions

Temperature
25 °C

Procedure

A mixture of 5-phenoxypicolinic acid (83 mg, 0.39 mmol), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (191 mg, 1 mmol), N-hydroxybenzotriazole (135 mg, 1 mmol), triethylamine (0.2 mL) and dichloromethane (5 mL) was stirred at 25° C. for 0.5 hour. And then 3-(aminomethyl)-4,6-dimethylpyridin-2-ol (76 mg, 0.5 mmol) was added to the mixture. The resultant mixture was stirred at 25° C. for 12 hours. Then water (20 ml) was added to the mixture and the mixture was extracted with dichloromethane (30 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 N-((2-hydroxy-4,6-dimethylpyridin-3-yl)methyl)-5-phenoxypicolinamide (Compound I-21) as a white solid (50 mg, 37%). LRMS (M+H+) m/z: calcd 349.15. found 349. HPLC purity (214 nm): 99%. 1H NMR (300 MHz, d6-DMSO): δ 11.53 (s, 1H), 8.56 (t, J=6.0 Hz, 1H), 8.37-8.36 (m, 1H), 8.01 (d, J=8.7 Hz, 1H), 7.48-7.42 (m, 3H), 7.26-7.16 (m, 3H), 5.86 (s, 1H), 4.32 (d, J=6.0 Hz, 2H), 2.22 (s, 3H), 2.10 (s, 3H).

Workup

  1. extractionthe mixture was extracted with dichloromethane (30 mL×3)
  2. dry with materialThe combined organic phase was dried by sodium sulfate
  3. filtrationfiltered
  4. concentrationThe filtrate was concentrated in vacuo
  5. customThe residue was purified by column chromatography (silica gel, dichloromethane/methanol=20:1)

Sources & evidence

ORD record
ord-d55a54ab6c9c4a29b784ecaf7b07cb17
Source dataset
uspto-grants-2015_12
Patent number
US09206128B2

Reaction notes

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