1,2-Diaminocyclohexane, trans- → HCID 118036345, compound

HRID 1778060Notes

Reaction equation

HRID 1778060 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][CH:18]1[CH2:22][CH2:21][NH:20][C:19]1=[O:23].[O-]P([O-])([O-])=O.[K+].[K+].[K+].N[C@@H]1CCCC[C@H]1N>O1CCOCC1.C(OCC)(=O)C.O.[Cu]I>[CH3:14][O:13][CH:12]([O:15][CH3:16])[C:11]1[C:2]([N:20]2[CH2:21][CH2:22][CH:18]([CH3:17])[C:19]2=[O:23])=[CH:3][C:4]2[CH2:5][CH2:6][CH2:7][NH:8][C:9]=2[N:10]=1

Participants

9

Reactant 4

HCID 438061,2-Diaminocyclohexane, trans-HCID 62657Potassium Phosphate, TribasicHCID 1028483-Methylpyrrolidin-2-oneHCID 1180362976-Bromo-7-(dimethoxymethyl)-1,2,3,4-tetrahydro-1,8-naphthyridine2×

Product 1

HCID 118036345HCID 118036345, compound

Reagents, catalysts & solvents 4

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 962WaterSolventHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
120 °C

Procedure

A suspension of 6-bromo-7-(dimethoxymethyl)-1,2,3,4-tetrahydro-1,8-naphthyridine (intermediate 12, 150 mg, 0.522 mmol), (racemic) 3-methylpyrrolidin-2-one (75 mg, 0.719 mmol), K3PO4 (235 mg, 1.107 mmol) and CuI (10 mg, 0.053 mmol) in dioxane (1 ml) was heated to 120° C. for 135 min. The reaction mixture was cooled to room temperature, (1R,2R)-(−)-1,2-diaminocyclohexane (7 μL, 0.058 mmol) was added and the mixture was heated to 120° C. and stirred for 10 h. The reaction mixture was diluted with ethyl acetate and water, layers were separated and the aqueous layer was extracted with ethyl acetate. 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 a brown solid. (UPLC-MS 3) tR 0.55 min; ESI-MS 306.1 [M+H]+.

Workup

  1. temperatureThe reaction mixture was cooled to room temperature
  2. temperaturethe mixture was heated to 120° C.
  3. customwere separated
  4. extractionthe aqueous layer was extracted with ethyl acetate
  5. washwashed with water and brine
  6. customdried
  7. filtrationfiltered
  8. customevaporated
  9. customThe crude product was purified by silica gel column chromatography
  10. washeluting with a gradient of MeOH (1-10%) in DCM
  11. customevaporated
  12. customdried

Sources & evidence

ORD record
ord-05f78c9d29304c4f82fc17affa11dea9
Source dataset
uspto-grants-2016_02
Patent number
US09266883B2

Reaction notes

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