Imidazole → 7-(Dimethoxymethyl)-1,2,3,4-tetrahydro-6-(1H-imidazol-1-yl)-1,8-naphthyridine

HRID 1778055Notes

Reaction equation

HRID 1778055 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:9](=[N:10][C:11]=1[CH:12]([O:15][CH3:16])[O:13][CH3:14])[NH:8][CH2:7][CH2:6][CH2:5]2.[NH:17]1[CH:21]=[CH:20][N:19]=[CH:18]1.C([O-])([O-])=O.[Cs+].[Cs+]>CN(C=O)C.C(OCC)(=O)C.O.[Cu]I>[CH3:14][O:13][CH:12]([O:15][CH3:16])[C:11]1[N:10]=[C:9]2[C:4]([CH2:5][CH2:6][CH2:7][NH:8]2)=[CH:3][C:2]=1[N:17]1[CH:21]=[CH:20][N:19]=[CH:18]1

Participants

8

Reactant 3

HCID 795ImidazoleHCID 10796Cesium carbonateHCID 1180362976-Bromo-7-(dimethoxymethyl)-1,2,3,4-tetrahydro-1,8-naphthyridine2×

Product 1

HCID 1180367227-(Dimethoxymethyl)-1,2,3,4-tetrahydro-6-(1H-imidazol-1-yl)-1,8-naphthyridine

Reagents, catalysts & solvents 4

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
120 °C

Procedure

A suspension of 6-bromo-7-(dimethoxymethyl)-1,2,3,4-tetrahydro-1,8-naphthyridine (intermediate 12, 200 mg, 0.696 mmol), imidazole (66 mg, 0.969 mmol), Cs2CO3 (454 mg, 1.393 mmol) and CuI (27 mg, 0.142 mmol) in DMF (1.4 ml) was heated to 120° C. for 19 h. The reaction mixture was diluted with ethyl acetate and water, layers were separated and the aqueous layer was extracted with ethyl acetate (7×). Organic layers were combined, washed with water and brine, dried using Na2SO4, filtered, evaporated and dried to yield the title compound as a yellow solid. (UPLC-MS 3) tR 0.45 min, ESI-MS 275.1 [M+H]+.

Workup

  1. customwere separated
  2. extractionthe aqueous layer was extracted with ethyl acetate (7×)
  3. washwashed with water and brine
  4. customdried
  5. filtrationfiltered
  6. customevaporated
  7. customdried

Sources & evidence

ORD record
ord-6fb5e930cbfd4e71aa2d4ee15fa7fa20
Source dataset
uspto-grants-2016_02
Patent number
US09266883B2

Reaction notes

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