Cesium carbonate → HCID 118036442, compound

HRID 1778058Notes

Reaction equation

HRID 1778058 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.[CH3:17][C:18]1[N:22]=[CH:21][NH:20][N:19]=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:20]1[CH:21]=[N:22][C:18]([CH3:17])=[N:19]1

Participants

8

Reactant 3

HCID 10796Cesium carbonateHCID 1180362976-Bromo-7-(dimethoxymethyl)-1,2,3,4-tetrahydro-1,8-naphthyridine2×HCID 178433329HCID 178433329, compound

Product 1

HCID 118036442HCID 118036442, compound

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) (300 mg, 1.045 mmol), 3-methyl-1H-1,2,4-triazole (104 mg, 1.254 mmol), Cs2CO3 (720 mg, 2.210 mmol) and CuI (40 mg, 0.210 mmol) in DMF (2 ml) was heated to 120° C. for approximately 6 h. The reaction mixture was diluted with ethyl acetate and water, layers were separated and the aqueous layer was extracted with ethyl acetate (3×). Organic layers were combined, washed with water and brine, dried using Na2SO4, filtered, evaporated. The crude product was purified by silica gel column chromatography eluting with a gradient of MeOH (1-10%) in DCM. Product fractions were combined, evaporated and dried to yield the title compound as an orange resin. (UPLC-MS 3) tR 0.57 min; ESI-MS 290.1 [M+H]+. 1H NMR (400 MHz, CDCl3) δ 8.21 (s, 1H), 7.21 (s, 1H), 5.35 (s, 1H), 4.95 (s, 1H), 3.51-3.41 (m, 2H), 3.36 (s, 6H), 2.75 (t, 2H), 2.47 (s, 3H), 1.97-1.86 (m, 2H).

Workup

  1. customwere separated
  2. extractionthe aqueous layer was extracted with ethyl acetate (3×)
  3. washwashed with water and brine
  4. customdried
  5. filtrationfiltered
  6. customevaporated
  7. customThe crude product was purified by silica gel column chromatography
  8. washeluting with a gradient of MeOH (1-10%) in DCM
  9. customevaporated
  10. customdried

Sources & evidence

ORD record
ord-a4a3b52c52af4fa4b6c0a9093d53bb7b
Source dataset
uspto-grants-2016_02
Patent number
US09266883B2

Reaction notes

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