1,10-Phenanthroline → HCID 66733796, compound

HRID 1929711Notes

Reaction equation

HRID 1929711 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]2[C:14]([CH:18]([CH3:20])[CH3:19])=[N:15][C:16](I)=[C:10]2[CH:9]1[CH2:21][CH2:22][C:23]1[CH:28]=[CH:27][C:26]([C:29]([F:32])([F:31])[F:30])=[CH:25][CH:24]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].N1C2C(=CC=C3C=2N=CC=C3)C=CC=1.[C:47](=O)([O-])[O-:48].[Cs+].[Cs+]>CO.[Cu]I>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]2[C:14]([CH:18]([CH3:20])[CH3:19])=[N:15][C:16]([O:48][CH3:47])=[C:10]2[CH:9]1[CH2:21][CH2:22][C:23]1[CH:28]=[CH:27][C:26]([C:29]([F:32])([F:31])[F:30])=[CH:25][CH:24]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

6

Reactant 3

HCID 13181,10-PhenanthrolineHCID 10796Cesium carbonateHCID 66734032HCID 66734032, compound

Product 1

HCID 66733796HCID 66733796, compound

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 887MethanolSolvent

Procedure

A solution of 1-iodo-3-isopropyl-8-[2-(4-trifluoromethyl-phenyl)-ethyl]-5,6-dihydro-8H-imidazo[1,5-a]pyrazine-7-carboxylic acid tert-butyl ester (150 mg; 0.266 mmol) in anhydrous MeOH (3 ml) was treated successively with copper(I) iodide (5 mg; 0.026 mmol), 1,10-phenanthroline (10.5 mg; 0.053 mmol), and cesium carbonate (138.8 mg; 0.426 mmol). The resulting brown suspension was sealed and put in the microwave oven (35 W; 100° C.; 6 bars; 1 h). This microwave-assisted methoxylation was repeated two additional times with the same amount of starting material. The resulting mixed brown suspension was concentrated to dryness under reduced pressure and the crude was purified by preparative HPLC. The expected product 3-isopropyl-1-methoxy-8-[2-(4-trifluoromethyl-phenyl)-ethyl]-5,6-dihydro-8H-imidazo[1,5-a]pyrazine-7-carboxylic acid tert-butyl ester was obtained as a yellow oil (107.5 mg; 29%). LC-MS: tR=0.94 min.; [M+H]+=468.55 g/mol.

Workup

  1. customThe resulting brown suspension was sealed
  2. customput in the microwave oven (35 W; 100° C.; 6 bars; 1 h)
  3. additionThe resulting mixed brown suspension
  4. concentrationwas concentrated to dryness under reduced pressure
  5. customthe crude was purified by preparative HPLC

Sources & evidence

ORD record
ord-2487df0c7a2d4c35a9c0f4c1881f2303
Source dataset
uspto-grants-2012_05
Patent number
US08188082B2

Reaction notes

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