Triethylamine → HCID 178425181, compound

HRID 1501228Notes

Reaction equation

HRID 1501228 reaction equation
[N:1]1[CH:6]=[CH:5][C:4]([O:7][CH:8]([C:10]2[CH:18]=[CH:17][C:13]([C:14]([OH:16])=O)=[CH:12][CH:11]=2)[CH3:9])=[N:3][CH:2]=1.N1(O)C2C=CC=CC=2N=N1.Cl.CN(C)CCCN=C=NCC.C(N(CC)CC)C.[NH2:48][CH2:49][C:50]1[C:51]([OH:58])=[N:52][C:53]([CH3:57])=[CH:54][C:55]=1[CH3:56]>ClCCl.O>[OH:58][C:51]1[C:50]([CH2:49][NH:48][C:14](=[O:16])[C:13]2[CH:12]=[CH:11][C:10]([CH:8]([O:7][C:4]3[CH:5]=[CH:6][N:1]=[CH:2][N:3]=3)[CH3:9])=[CH:18][CH:17]=2)=[C:55]([CH3:56])[CH:54]=[C:53]([CH3:57])[N:52]=1

Participants

8

Reactant 5

HCID 8471TriethylamineHCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 89580475HCID 89580475, compoundHCID 178425242HCID 178425242, compound

Product 1

HCID 178425181HCID 178425181, compoundYield 40%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of 4-(1-(pyrimidin-4-yloxy)ethyl)benzoic acid (0.1 g, 0.4 mmol) in anhydrous dichloromethane (20 mL) was added 1H-benzo[d][1,2,3]triazol-1-ol (85 mg, 0.6 mmol), 1-(3-Dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (120 mg, 0.6 mmol) and triethylamine (0.2 mL, 1.2 mmol), and stirred at room temperature for 0.5 hour, 3-(aminomethyl)-4,6-dimethylpyridin-2-ol (90 mg, 0.6 mmol) was added and stirred for 3 hours. To the reaction mixture was added water (20 mL), extracted with dichloromethane (20 mL) two times, combined and concentrated the organic layers, the residue was purified by column chromatography with dichloromethane/methanol=15:1 to afford N-((2-hydroxy-4,6-dimethylpyridin-3-yl)methyl)-4-(1-(pyrimidin-4-yloxy)ethyl)benzamide (60 mg, 40% yield). LRMS (M+H+) m/z: calcd for 378.17. found 378. HPLC purity (214 nm): 98%. 1H NMR (CD3OD, 300 MHz) δ 8.67 (s, 1H), 8.46 (d, J=6.0 Hz, 1H), 7.81 (d, J=8.1 Hz, 2H), 7.53 (d, J=8.4 Hz, 2H), 6.98 (dd, J=6.0 and 1.2 Hz, 1H), 6.36 (q, J=6.6 Hz, 1H), 6.15 (s, 1H), 4.52 (s, 2H), 2.39 (s, 3H), 2.28 (s, 3H), 1.69 (d, J=8.7 Hz, 3H).

Workup

  1. stirringstirred for 3 hours
  2. extractionextracted with dichloromethane (20 mL) two times
  3. concentrationconcentrated the organic layers
  4. customthe residue was purified by column chromatography with dichloromethane/methanol=15:1

Sources & evidence

ORD record
ord-4f59712b7fd04d70934dd3da84fcc1de
Source dataset
uspto-grants-2015_12
Patent number
US09206128B2

Reaction notes

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