1-Hydroxybenzotriazole → HCID 89544209, compound

HRID 1050949Notes

Reaction equation

HRID 1050949 reaction equation
[F:1][C:2]1[CH:24]=[CH:23][C:5]([O:6][C:7]2[CH:12]=[CH:11][C:10]([C:13]3[CH:14]=[C:15]([CH:19]=[C:20]([CH3:22])[N:21]=3)[C:16](O)=[O:17])=[CH:9][CH:8]=2)=[CH:4][CH:3]=1.ON1C2C=CC=CC=2N=N1.[O:35]1[CH2:40][CH2:39][N:38]([CH2:41][CH2:42][NH2:43])[CH2:37][CH2:36]1>C(Cl)Cl>[F:1][C:2]1[CH:3]=[CH:4][C:5]([O:6][C:7]2[CH:12]=[CH:11][C:10]([C:13]3[CH:14]=[C:15]([CH:19]=[C:20]([CH3:22])[N:21]=3)[C:16]([NH:43][CH2:42][CH2:41][N:38]3[CH2:39][CH2:40][O:35][CH2:36][CH2:37]3)=[O:17])=[CH:9][CH:8]=2)=[CH:23][CH:24]=1

Participants

5

Reactant 3

HCID 757711-HydroxybenzotriazoleHCID 4082852-MorpholinoethylamineHCID 89544099HCID 89544099, compound

Product 1

HCID 89544209HCID 89544209, compoundYield 36.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

In a 50 mL vial with a screw-top septum 2-(4-(4-fluorophenoxy)phenyl)-6-methylisonicotinic acid (300 mg, 0.9 mmol) was dissolved in DCM (5 mL). To the solution were added 1-ethyl-3-(3-dimethyl-aminopropyl) carbodiimide (144 mg, 0.9 mmol) and 1-hydroxybenzotriazole (63 mg, 0.46 mmol). The reaction mixture was stirred for 20 minutes at room temperature. Then, 2-morpholinoethanamine (121 mg, 0.9 mmol) was added. The reaction mixture was stirred for 20 hours at room temperature and was then chromatographed directly by combiflash without workup using a 40-gram silica column and a gradient of MeOH (40% max) in chloroform to provide 2-(4-(4-fluorophenoxy)phenyl)-6-methyl-N-(2-morpholinoethyl) isonicotinamide as a clear oil (142 mg). 1H NMR (CD3OD): 8.05-7.99 (m, 2 H), 7.98 7.94 (m, 1 H), 7.56-7.51 (m, 1 H), 7.19-7.03 (s, 6 H), 3.75-3.67 (m, 4 H), 3.62-3.54 (m, 2 H), 2.68-2.60 (m, 5 H), 2.59-2.52 (m, 4 H). LCMS: m/z=436 [M+H+]+.

Workup

  1. stirringThe reaction mixture was stirred for 20 hours at room temperature
  2. customwas then chromatographed directly by combiflash without workup

Sources & evidence

ORD record
ord-0ae36a3f9f204848bae33fd3958af331
Source dataset
uspto-grants-2016_07
Patent number
US09388137B2

Reaction notes

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