N-Methyl dicyclohexylamine → benzyl 2-oxo-1-{[2-(trimethylsilyl)ethoxy]methyl}-2,2',3,3'-tetrahydro-1H,1'H-spiro[1,8-naphthyridine-4,4'-pyridine]-1'-carboxylate

HRID 550399Notes

Reaction equation

HRID 550399 reaction equation
CN(C1CCCCC1)C1CCCCC1.Br[C:16]1[C:17]([N:22]([CH2:42][O:43][CH2:44][CH2:45][Si:46]([CH3:49])([CH3:48])[CH3:47])[C:23](=[O:41])[CH2:24][C:25]2[CH2:26][CH2:27][N:28]([C:31]([O:33][CH2:34][C:35]3[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=3)=[O:32])[CH2:29][CH:30]=2)=[N:18][CH:19]=[CH:20][CH:21]=1>O1CCOCC1.O.[Pd].C(P(C(C)(C)C)C(C)(C)C)(C)(C)C.C(P(C(C)(C)C)C(C)(C)C)(C)(C)C>[O:41]=[C:23]1[CH2:24][C:25]2([CH:26]=[CH:27][N:28]([C:31]([O:33][CH2:34][C:35]3[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=3)=[O:32])[CH2:29][CH2:30]2)[C:16]2[C:17](=[N:18][CH:19]=[CH:20][CH:21]=2)[N:22]1[CH2:42][O:43][CH2:44][CH2:45][Si:46]([CH3:49])([CH3:48])[CH3:47]

Participants

6

Reactant 2

HCID 24210N-Methyl dicyclohexylamineHCID 59555191benzyl 4-[2-((3-bromopyridin-2-yl){[2-(trimethylsilyl)ethoxy]methyl}amino)-2-oxoethyl]-3,6-dihydropyridine-1(2H)-carboxylate

Product 1

HCID 57663850benzyl 2-oxo-1-{[2-(trimethylsilyl)ethoxy]methyl}-2,2',3,3'-tetrahydro-1H,1'H-spiro[1,8-naphthyridine-4,4'-pyridine]-1'-carboxylateYield 79.6%

Reagents, catalysts & solvents 3

HCID 2734558Bis(tri-tert-butylphosphine)palladium(0)Catalyst2×HCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
50 °C

Procedure

To a mixture of N-methyldicyclohexylamine (0.042 mg, 0.20 mmol) and benzyl 4-[2-((3-bromopyridin-2-yl) {[2-(trimethylsilyl)ethoxy]methyl}amino)-2-oxoethyl]-3,6-dihydropyridine-1(2H)-carboxylate (100 mg, 0.178 mmol) in dioxane (2 mL) was added bis(tri-tert-butylphosphine) palladium(0) (9 mg, 0.018 mmol). After 5 min, the reaction was heated to 50° C. After 90 min, bis(tri-tert-butylphosphine) palladium(0) (9 mg) was added. After an additional 30 min at 50° C., the reaction mixture was diluted with water and extracted with ether (3×). The combined organic layers were dried over MgSO4, filtered, and concentrated. The crude product was purified by silica gel chromatography, eluting with a gradient of 5 to 60% ethyl acetate:hexanes to give the title compound (68 mg). MS: m/z=480.2 (M+1).

Workup

  1. waitAfter 90 min
  2. waitAfter an additional 30 min at 50° C.
  3. extractionextracted with ether (3×)
  4. dry with materialThe combined organic layers were dried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe crude product was purified by silica gel chromatography
  8. washeluting with a gradient of 5 to 60% ethyl acetate

Sources & evidence

ORD record
ord-587b1b9ecd3240d1ab694053b60a766f
Source dataset
uspto-grants-2011_05
Patent number
US07947678B2

Reaction notes

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