Glycine → HCID 67050740, compound

HRID 886451Notes

Reaction equation

HRID 886451 reaction equation
Br[C:2]1[CH:23]=[CH:22][C:5]2[C:6]3[N:10]([CH2:11][CH2:12][O:13][C:4]=2[CH:3]=1)[CH:9]=[C:8]([C:14]1[N:15]([CH:19]([CH3:21])[CH3:20])[N:16]=[CH:17][N:18]=1)[N:7]=3.[NH2:24][CH2:25][C:26]([OH:28])=[O:27].O[C@H:30]1CN[C@H](C(O)=O)C1.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>CS(C)=O.[Cu]I>[CH3:30][O:27][C:26](=[O:28])[CH2:25][NH:24][C:2]1[CH:23]=[CH:22][C:5]2[C:6]3[N:10]([CH2:11][CH2:12][O:13][C:4]=2[CH:3]=1)[CH:9]=[C:8]([C:14]1[N:15]([CH:19]([CH3:21])[CH3:20])[N:16]=[CH:17][N:18]=1)[N:7]=3

Participants

7

Reactant 4

HCID 750GlycineHCID 5810L-HydroxyprolineHCID 62657Potassium Phosphate, TribasicHCID 582043138-bromo-2-(2-isopropyl-2H-[1,2,4]triazol-3-yl)-4,5-dihydro-6-oxa-1,3a-diaza-benzo[e]azulene

Product 1

HCID 67050740HCID 67050740, compoundYield 98.5%

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 679Dimethyl SulfoxideSolvent

Procedure

8-Bromo-2-(2-isopropyl-2H-[1,2,4]triazol-3-yl)-4,5-dihydro-6-oxa-1,3a-diaza-benzo[e]azulene (1.0 g, 2.7 mmol), glycine (2.0 g, 27 mmol), copper (I) iodide (0.2 g, 1.08 mmol), trans-4-hydroxy-(L)-proline (0.14 g, 1.08 mmol) and potassium phosphate (1.14 g, 5.4 mmol) in DMSO (10 mL) were heated under nitrogen at 80° C. for 18 h. The reaction mixture was cooled to RT, concentrated in vacuo, loaded onto an SCX-2 cartridge, washed with methanol and eluted with 2M ammonia in methanol. Basic fractions were combined and concentrated in vacuo and the resultant residue was subjected to flash chromatography (SiO2, gradient 0 to 10% methanol in DCM) to give [2-(2-Isopropyl-2H-[1,2,4]triazol-3-yl)-4,5-dihydro-6-oxa-1,3a-diaza-benzo[e]azulen-8-ylamino]-acetic acid methyl ester (0.407 g, 39% total). 1H NMR 400 MHz (CDCl3) δ: 8.32 (1H, d, J=8.78 Hz), 7.55 (1H, s), 7.26 (1H, s), 6.46 (1H, dd, J=8.79, 2.45 Hz), 6.18 (1H, d, J=2.42 Hz), 6.00 (1H, m), 4.46-4.45 (2H, m), 4.41-4.35 (2H, m), 3.94 (2H, d, J=5.39 Hz), 3.80 (3H, s), 1.59 (6H, t, J=6.88 Hz).

Workup

  1. concentrationconcentrated in vacuo
  2. washwashed with methanol
  3. washeluted with 2M ammonia in methanol
  4. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-34ea71fa0a934dd9affa2018fcb62b74
Source dataset
uspto-grants-2012_08
Patent number
US08242104B2

Reaction notes

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