1,2-Dichloroethane → HCID 67136005, compound

HRID 1631029Notes

Reaction equation

HRID 1631029 reaction equation
[OH:1][N:2]=[C:3]([NH2:12])[C:4]1[CH:9]=[CH:8][N:7]=[C:6]([CH2:10][OH:11])[CH:5]=1.Br[C:14]1[CH:23]=[CH:22][C:17]([C:18]([O:20][CH3:21])=O)=[CH:16][C:15]=1[CH2:24]OC.[CH2:27](Cl)[CH2:28]Cl>CC#N.N1C=CC=CC=1>[CH3:21][O:20][CH2:18][C:17]1[CH:16]=[C:15]([C:24]2[O:1][N:2]=[C:3]([C:4]3[CH:9]=[CH:8][N:7]=[C:6]([CH2:10][OH:11])[CH:5]=3)[N:12]=2)[CH:14]=[CH:23][C:22]=1[C:8]1[CH:9]=[CH:4][CH:5]=[CH:6][C:27]=1[CH3:28]

Participants

6

Reactant 3

HCID 111,2-DichloroethaneHCID 58554220Methyl 4-bromo-3-(methoxymethyl)benzoateHCID 136359924HCID 136359924, compound

Product 1

HCID 67136005HCID 67136005, compound

Reagents, catalysts & solvents 2

HCID 1049PyridineSolventHCID 6342AcetonitrileSolvent

Procedure

To a solution of N′-hydroxy-2-(hydroxymethyl)isonicotinimidamide (Example 66, Step 1; 0.100 g; 0.30 mmol) and Intermediate A1 (0.108 g; 0.42 mmol) in MeCN (3 mL) was added EDC (0.060 g; 0.38 mmol). The reaction mixture was stirred at ambient temperature for 18 h. The reaction mixture was diluted with pyridine (2 mL) and heated at 150° C. in the microwave for 30 minutes. This process was repeated 4 times and combined for work-up. The solvent was removed in vacuo and the residue dissolved in DCM. The mixture was washed with water and the organic phase passed through a hydrophobic frit. The solvent was evaporated in vacuo. The residue was purified by flash chromatography on silica, eluting with iso-hexane/EtOAc (100% iso-hexane to 100% EtOAc) to afford the title compound. 1H NMR (CDCl3, 400 MHz) δ 8.76 (1 H, d, J=5.2 Hz), 8.44 (1 H, s), 8.18 (1 H, dd, J=7.9, 1.9 Hz), 8.06 (1 H, s), 7.99 (1 H, d, J=5.2 Hz), 7.39-7.22 (4 H, m), 7.13 (1 H, d, J=7.5 Hz), 4.90 (2 H, s), 4.28-4.18 (2 H, m), 3.65 (1 H, br s), 3.34 (3 H, s), 2.08 (3 H, s). LC/MS: 388 (M+H)+. HPLC (Method B) Rt 3.91 min (Purity: 98.1%).

Workup

  1. temperatureheated at 150° C. in the microwave for 30 minutes
  2. customThe solvent was removed in vacuo
  3. dissolutionthe residue dissolved in DCM
  4. washThe mixture was washed with water
  5. customThe solvent was evaporated in vacuo
  6. customThe residue was purified by flash chromatography on silica
  7. washeluting with iso-hexane/EtOAc (100% iso-hexane to 100% EtOAc)

Sources & evidence

ORD record
ord-8abbd018f9084e869f932624707244d4
Source dataset
uspto-grants-2014_07
Patent number
US08791142B2

Reaction notes

Loading…