Triethylamine → HCID 178425170, compound

HRID 1501115Notes

Reaction equation

HRID 1501115 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([CH:8]=[CH:9][C:10]=1[CH:11]([O:13][C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)[CH3:12])[C:5]([OH:7])=O.ON1C2C=CC=CC=2N=N1.Cl.CN(C)CCCN=C=NCC.C(N(CC)CC)C.[NH2:49][CH2:50][C:51]1[C:52]([OH:59])=[N:53][C:54]([CH3:58])=[CH:55][C:56]=1[CH3:57]>ClCCl.O>[F:1][C:2]1[CH:3]=[C:4]([CH:8]=[CH:9][C:10]=1[CH:11]([O:13][C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)[CH3:12])[C:5]([NH:49][CH2:50][C:51]1[C:52]([OH:59])=[N:53][C:54]([CH3:58])=[CH:55][C:56]=1[CH3:57])=[O:7]

Participants

8

Reactant 5

HCID 8471TriethylamineHCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 89581389HCID 89581389, compoundHCID 178425242HCID 178425242, compound

Product 1

HCID 178425170HCID 178425170, compoundYield 46%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

A solution of 3-fluoro-4-(1-phenoxyethyl)benzoic acid (300 mg, 1.2 mmol) in dichloromethane (15.0 mL) was added N-hydroxybenzotriazole (270 mg, 2 mmol), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (384 mg, 2 mmol), triethylamine (202 mg, 2 mmol). The mixture was stirred for 30 minutes. Then 3-(aminomethyl)-4,6-dimethylpyridin-2-ol (270 mg, 1.8 mmol) was added and the mixture was stirred at room temperature for 12 hours. To the mixture, water (50 mL) was added. The mixture was extracted with dichloromethane (2*50 mL). The combined organic phase was separated, dried over sodium sulfate, filtered and concentrated to give a residue. The residue was purified by preparative-TLC (silica gel, methanol/dichloromethane=1:20, 1% NH3) to give 3-fluoro-N-((2-hydroxy-4,6-dimethylpyridin-3-yl)methyl)-4-(1-phenoxyethyl)benzamide as white solid (217 mg, 46%). LRMS (M+H+) m/z: calcd 394.17. found 394. HPLC purity (214 nm): 96%. 1H NMR (300 MHz, CD3OD): δ 7.57-7.49 (m, 3H), 7.16 (t, J=8.4 Hz, 2H), 6.85-6.82 (m, 3H), 6.09 (s, 1H), 5.68 (q, J=6.6 Hz, 1H), 4.45 (s, 2H), 2.34 (s, 3H), 2.23 (s, 3H), 1.62 (d, J=8.4 Hz, 3H).

Workup

  1. stirringthe mixture was stirred at room temperature for 12 hours
  2. extractionThe mixture was extracted with dichloromethane (2*50 mL)
  3. customThe combined organic phase was separated
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customto give a residue
  8. customThe residue was purified by preparative-TLC (silica gel, methanol/dichloromethane=1:20, 1% NH3)

Sources & evidence

ORD record
ord-ff5973bb661a4e7f8b3d4bb23ac12877
Source dataset
uspto-grants-2015_12
Patent number
US09206128B2

Reaction notes

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