1-Hydroxybenzotriazole → HCID 178425174, compound

HRID 1501050Notes

Reaction equation

HRID 1501050 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([CH:17]=[CH:18][CH:19]=1)[O:5][CH:6]([C:8]1[CH:16]=[CH:15][C:11]([C:12]([OH:14])=O)=[CH:10][CH:9]=1)[CH3:7].Cl.C(N=C=NCCCN(C)C)C.ON1C2C=CC=CC=2N=N1.[NH2:42][CH2:43][C:44]1[C:45]([OH:52])=[N:46][C:47]([CH3:51])=[CH:48][C:49]=1[CH3:50]>O.ClCCl.C(N(CC)CC)C>[F:1][C:2]1[CH:3]=[C:4]([CH:17]=[CH:18][CH:19]=1)[O:5][CH:6]([C:8]1[CH:9]=[CH:10][C:11]([C:12]([NH:42][CH2:43][C:44]2[C:45]([OH:52])=[N:46][C:47]([CH3:51])=[CH:48][C:49]=2[CH3:50])=[O:14])=[CH:15][CH:16]=1)[CH3:7]

Participants

8

Reactant 4

HCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 89580996HCID 89580996, compoundHCID 178425242HCID 178425242, compound

Product 1

HCID 178425174HCID 178425174, compoundYield 34.2%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6344DichloromethaneSolventHCID 8471TriethylamineSolvent

Conditions

Temperature
25 °C

Procedure

A mixture of 4-(1-(3-fluorophenoxy)ethyl)benzoic acid (260 mg, 1 mmol), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (382 mg, 2 mmol), N-hydroxybenzotriazole (270 mg, 2 mmol), triethylamine (0.3 mL) and dichloromethane (15 mL) were stirred at 25° C. for half an hour. And then 3-(aminomethyl)-4,6-dimethylpyridin-2-ol (152 mg, 1 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 4-(1-(3-fluorophenoxy)ethyl)-N-((2-hydroxy-4,6-dimethylpyridin-3-yl)methyl)benzamide (Compound I-42) (135 mg, 34%). LRMS (M+H+) m/z: calcd. 394.17. found 394. HPLC purity (214 nm): 91%. 1H NMR (300 MHz, d6-DMSO): δ 11.44 (s, 1H), 8.30 (t, J=4.8 Hz, 1H), 7.78 (d, J=8.4 Hz, 2H), 7.43 (d, J=8.1 Hz, 2H), 7.20 (q, J=8.1 Hz, 1H), 6.77-6.64 (m, 3H), 5.83 (s, 1H), 5.57 (q, J=6.3 Hz, 1H), 4.27 (d, J=4.8 Hz, 2H), 2.15 (s, 3H), 2.10 (s, 3H), 1.53 (d, J=6.0 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-0f87433efb6644bfb6faf80cf2caf0e2
Source dataset
uspto-grants-2015_12
Patent number
US09206128B2

Reaction notes

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