N-Methyl dicyclohexylamine → HCID 86706125, compound

HRID 2176279Notes

Reaction equation

HRID 2176279 reaction equation
[C:1]([O:5][C:6](=[O:21])[NH:7][C@@H:8]([C:10]1[CH:19]=[CH:18][C:17]2[C:12](=[CH:13][C:14](Br)=[CH:15][CH:16]=2)[N:11]=1)[CH3:9])([CH3:4])([CH3:3])[CH3:2].[CH3:22][O:23][CH2:24][C@:25]([CH3:31])([CH:29]=[CH2:30])[C:26]([OH:28])=[O:27].C1(C)C=CC=CC=1P(C1C=CC=CC=1C)C1C=CC=CC=1C.C1(N(C)C2CCCCC2)CCCCC1.S([O-])(O)(=O)=O.[K+]>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.O1CCOCC1.C(#N)C>[C:1]([O:5][C:6]([NH:7][C@@H:8]([C:10]1[CH:19]=[CH:18][C:17]2[C:12](=[CH:13][C:14](/[CH:30]=[CH:29]/[C@:25]([CH2:24][O:23][CH3:22])([CH3:31])[C:26]([OH:28])=[O:27])=[CH:15][CH:16]=2)[N:11]=1)[CH3:9])=[O:21])([CH3:4])([CH3:3])[CH3:2]

Participants

9

Reactant 5

HCID 24210N-Methyl dicyclohexylamineHCID 80271Tri-o-tolylphosphineHCID 516920Potassium bisulfateHCID 86706059HCID 86706059, compoundHCID 86706123HCID 86706123, compound

Product 1

HCID 86706125HCID 86706125, compoundYield 21.2%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 6342AcetonitrileSolventHCID 312751,4-DioxaneSolvent

Procedure

To a vial charged with [(R)-1-(7-bromo-quinolin-2-yl)-ethyl]-carbamic acid tert-butyl ester (706 mg, 2 mmol), (S)-2-methoxymethyl-2-methyl-but-3-enoic acid (290 mg, 2 mmol), tri-(o-tolyl)phosphine (610 mg, 2 mmol) and N,N-dicyclohexyl-methyl-amine (0.85 mL, 4 mmol), was added acetonitrile (2 mL) and 1,4-dioxane (6 mL). The vial was purged with nitrogen. Palladium(II) acetate (450 mg, 2 mmol) was added. The vial was sealed and irradiated by microwave at 130° C. for 1 h. The mixture was then treated with saturated solution of potassium hydrogen sulfate. The aqueous layer was extracted with ethyl acetate (2×) and the combined organic layers were washed with brine, dried over anhydrous sodium sulfate and filtered. The filtrate was evaporated. The crude residue was purified by silica gel chromatography using a Biotage KP-Sil 100 g cartridge eluting with a gradient of ethyl acetate/methanol 1:0 to 41:9 to give the title product (0.176 g, 21%) as an amber oil. 1H NMR (300 MHz, CDCl3) δ 1.45 (s, 9H), 1.54 (s, 3H), 1.57 (d, J=6.5 Hz, 3H), 3.47 (s, 3H), 3.62 (d, J=8.7 Hz, 1H), 3.77 (d, J=8.7 Hz, 1H), 4.90-5.10 (m, 1H), 6.60-6.85 (m, 2H), 7.34 (d, J=8.4 Hz, 1H), 7.61 (d, J=8.4 Hz, 1H), 7.75 (d, J=8.4 Hz, 1H), 8.06-8.17 (m, 2H). LCMS (m/z) 415.3 [M+H], Tr=2.11 min.

Workup

  1. customThe vial was purged with nitrogen
  2. customThe vial was sealed
  3. customirradiated by microwave at 130° C. for 1 h
  4. extractionThe aqueous layer was extracted with ethyl acetate (2×)
  5. washthe combined organic layers were washed with brine
  6. dry with materialdried over anhydrous sodium sulfate
  7. filtrationfiltered
  8. customThe filtrate was evaporated
  9. customThe crude residue was purified by silica gel chromatography
  10. washeluting with a gradient of ethyl acetate/methanol 1:0 to 41:9

Sources & evidence

ORD record
ord-21642282ab5e435baf03b1d68b82fe89
Source dataset
uspto-grants-2015_06
Patent number
US09062092B2

Reaction notes

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