Triethylamine → HCID 178425198, compound

HRID 1501054Notes

Reaction equation

HRID 1501054 reaction equation
[CH3:1][CH:2]([CH3:20])[CH:3]([C:11]1[CH:19]=[CH:18][C:14]([C:15]([OH:17])=O)=[CH:13][CH:12]=1)[O:4][C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(CC)CC)C.[NH2:52][CH2:53][C:54]1[C:55]([OH:62])=[N:56][C:57]([CH3:61])=[CH:58][C:59]=1[CH3:60]>ClCCl>[OH:62][C:55]1[C:54]([CH2:53][NH:52][C:15](=[O:17])[C:14]2[CH:13]=[CH:12][C:11]([CH:3]([O:4][C:5]3[CH:6]=[CH:7][CH:8]=[CH:9][CH:10]=3)[CH:2]([CH3:1])[CH3:20])=[CH:19][CH:18]=2)=[C:59]([CH3:60])[CH:58]=[C:57]([CH3:61])[N:56]=1

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 89580898HCID 89580898, compoundHCID 178425242HCID 178425242, compound

Product 1

HCID 178425198HCID 178425198, compoundYield 32.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
25 °C

Procedure

A mixture of 4-(2-methyl-1-phenoxypropyl)benzoic acid (208 mg, 0.77 mmol), o-(7-azabenzotriazol-1-yl)-N,N,N′,N′-te-tramethyluroniumhexafluorophosphate (439 mg, 1.2 mmol), triethylamine (0.32 mL) and dichloromethane (15 mL) were stirred at 25° C. for half an hour. Then 3-(aminomethyl)-4,6-dimethylpyridin-2-ol (152 mg, 1.0 mmol) was added. The mixture was stirred at 25° C. for 12 hours. The resultant mixture was washed with water (30 mL). The organic phase was separated, dried over sodium, filtered, concentrated to give a residue. The residue was purified by column chromatography (silica gel, dichloromethane/methanol=10:1) to give N-((2-hydroxy-4,6-dimethylpyridin-3-yl)methyl)-4-(2-methyl-1-phenoxypropyl)benzamide (Compound I-43) as a white solid (100 mg, 32%). LRMS (M+H+) m/z: calcd 404.21. found 404. HPLC purity (214 nm): 100%. 1H NMR (300 MHz, d6-DMSO): δ 11.46 (s, 1H), 8.33 (t, J=5.1 Hz, 1H), 7.47 (s, 1H), 7.34 (m, 3H), 7.20 (m, 3H), 6.88 (m, 2H), 5.84 (s, 1H), 5.54 (d, J=6.6 Hz, 1H), 4.25 (d, J=4.5 Hz, 2H), 2.35-2.30 (m, 1H), 2.17 (s, 3H), 2.13 (s, 3H), 1.01 (d, J=6.6 Hz, 6H).

Workup

  1. stirringThe mixture was stirred at 25° C. for 12 hours
  2. washThe resultant mixture was washed with water (30 mL)
  3. customThe organic phase was separated
  4. dry with materialdried over sodium
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customto give a residue
  8. customThe residue was purified by column chromatography (silica gel, dichloromethane/methanol=10:1)

Sources & evidence

ORD record
ord-1d8ab4d6eb4f4580b55ef4c407bc3515
Source dataset
uspto-grants-2015_12
Patent number
US09206128B2

Reaction notes

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