1-Hydroxybenzotriazole → HCID 178425188, compound

HRID 1501017Notes

Reaction equation

HRID 1501017 reaction equation
[O:1]([C@H:8]([C:10]1[CH:18]=[CH:17][C:13]([C:14]([OH:16])=O)=[CH:12][CH:11]=1)[CH3:9])[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.[NH2:41][CH2:42][C:43]1[C:44]([OH:51])=[N:45][C:46]([CH3:50])=[CH:47][C:48]=1[CH3:49]>O.ClCCl.C(N(CC)CC)C>[OH:51][C:44]1[C:43]([CH2:42][NH:41][C:14](=[O:16])[C:13]2[CH:12]=[CH:11][C:10]([C@@H:8]([O:1][C:2]3[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=3)[CH3:9])=[CH:18][CH:17]=2)=[C:48]([CH3:49])[CH:47]=[C:46]([CH3:50])[N:45]=1

Participants

8

Reactant 4

HCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 89581520HCID 89581520, compoundHCID 178425242HCID 178425242, compound

Product 1

HCID 178425188HCID 178425188, compoundYield 53.1%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6344DichloromethaneSolventHCID 8471TriethylamineSolvent

Conditions

Temperature
25 °C

Procedure

A mixture of (S)-4-(1-phenoxyethyl)benzoic acid (121 mg, 0.5 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) were stirred at 25° C. for half an hour. And then 3-(aminomethyl)-4,6-dimethylpyridin-2-ol (76 mg, 0.5 mmol) was added. The mixture was stirred at 25° C. for 12 hours. To the mixture, water (20 mL) was added 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 (S)—N-((2-hydroxy-4,6-dimethylpyridin-3-yl)methyl)-4-(1-phenoxyethyl)benzamide as a white solid (100 mg, 53%). LRMS (M+H+) m/z: calcd. 376.18. found 376. HPLC purity (214 nm): 100%. 1H NMR (300 MHz, d6-DMSO): δ 11.44 (s, 1H), 8.29-8.27 (m, 1H), 7.77 (d, J=8.1 Hz, 2H), 7.42 (d, J=8.1 Hz, 2H), 7.20-7.15 (m, 2H), 6.87-6.83 (m, 3H), 5.83 (s, 1H), 5.53-5.51 (m, 1H), 4.26 (d, J=5.1 Hz, 2H), 2.14 (s, 3H), 2.10 (s, 3H), 1.53 (d, J=6.6 Hz, 3H).

Workup

  1. stirringThe mixture was stirred at 25° C. for 12 hours
  2. extractionthe mixture was extracted with dichloromethane (30 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-84149c55e52341e4a9fc79945b5ecff3
Source dataset
uspto-grants-2015_12
Patent number
US09206128B2

Reaction notes

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