Morpholine → HCID 68621414, compound

HRID 2365244Notes

Reaction equation

HRID 2365244 reaction equation
Cl[C:2]1[N:7]=[CH:6][C:5]([CH2:8][C:9]2[C:10]3[CH:29]=[CH:28][CH:27]=[CH:26][C:11]=3[C:12]3[CH2:13][N:14]([C@H:19]4[CH2:24][CH2:23][CH2:22][CH2:21][C@@H:20]4[OH:25])[C:15](=[O:18])[C:16]=3[CH:17]=2)=[CH:4][CH:3]=1.[NH:30]1[CH2:35][CH2:34][O:33][CH2:32][CH2:31]1.CC(C)([O-])C.[Na+].C1C=CC(P(C2C=CC3C(=CC=CC=3)C=2C2C3C(=CC=CC=3)C=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C(=O)(O)[O-].[Na+]>C1(C)C=CC=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[OH:25][C@H:20]1[CH2:21][CH2:22][CH2:23][CH2:24][C@@H:19]1[N:14]1[CH2:13][C:12]2[C:11]3[CH:26]=[CH:27][CH:28]=[CH:29][C:10]=3[C:9]([CH2:8][C:5]3[CH:6]=[N:7][C:2]([N:30]4[CH2:35][CH2:34][O:33][CH2:32][CH2:31]4)=[CH:3][CH:4]=3)=[CH:17][C:16]=2[C:15]1=[O:18]

Participants

8

Reactant 5

HCID 8083MorpholineHCID 516892Sodium BicarbonateHCID 634876Binap, (A+-)-HCID 23676156Sodium t-butoxideHCID 86682401HCID 86682401, compound

Product 1

HCID 68621414HCID 68621414, compound

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolvent

Conditions

Temperature
110 °C

Procedure

To a solution of 5-[(6-chloropyridin-3-yl)methyl]-2-[(1S,2S)-2-hydroxycyclohexyl]-1,2-dihydro-3H-benzo[e]isoindol-3-one (0.101 g, 0.248 mmol) in 3 mL of toluene was added morpholine (0.032 g, 0.37 mmol), sodium tert-butoxide (0.60 g, 0.62 mmol), tris[dibenzylideneacetone]dipalladium (0) (0.034 g, 0.037 mmol), and (R)-(+)-2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (0.011 g, 0.017 mmol). The mixture was heated at 110° C. for 3 hr, cooled to ambient temperature, poured into saturated aqueous sodium bicarbonate (25 mL), and extracted twice with ethyl acetate. The combined organic extracts were washed with brine, dried with sodium sulfate, filtered, and concentrated in vacuo. The residue was purified via preparative reverse phase HPLC to provide the title compound that gave a proton NMR spectra consistent with theory and a mass ion (ES+) of 458.2 for [M+H]+: 1H NMR (400 MHz, CDCl3) δ 8.15 (s, 1H), 8.10-8.07 (m, 1H), 7.88-7.86 (m, 1H), 7.68 (s, 1H), 7.59-7.56 (m, 2H), 7.28-7.25 (m, 1H), 6.53 (d, J=8.8 Hz, 1H), 4.82-4.69 (m, 2H), 4.33 (s, 2H), 4.20-4.11 (m, 1H), 3.82-3.70 (m, 5H), 3.46-3.41 (m, 4H), 2.23-2.20 (m, 1H), 2.05-1.98 (m, 1H), 1.87-1.64 (m, 4H), 1.51-1.28 (m, 3H) ppm.

Workup

  1. temperaturecooled to ambient temperature
  2. extractionextracted twice with ethyl acetate
  3. washThe combined organic extracts were washed with brine
  4. dry with materialdried with sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified via preparative reverse phase HPLC

Sources & evidence

ORD record
ord-f713f2de86d8415885ea433c0231f0c2
Source dataset
uspto-grants-2014_04
Patent number
US08697690B2

Reaction notes

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