Triethylamine → HCID 25261851, compound

HRID 717255Notes

Reaction equation

HRID 717255 reaction equation
[C:1]([C:5]1[S:9][C:8](=[NH:10])[N:7]([CH2:11][C@H:12]2[CH2:16][CH2:15][CH2:14][O:13]2)[N:6]=1)([CH3:4])([CH3:3])[CH3:2].[CH2:17](N(CC)CC)C.[N+]([C:27]1[CH:32]=[CH:31][C:30]([NH:33][C:34](Cl)=[O:35])=[CH:29][CH:28]=1)([O-])=O.CC1CCC(N)CC1>O1CCCC1>[C:1]([C:5]1[S:9]/[C:8](=[N:10]\[C:34]([NH:33][CH:30]2[CH2:31][CH2:32][CH:27]([CH3:17])[CH2:28][CH2:29]2)=[O:35])/[N:7]([CH2:11][C@H:12]2[CH2:16][CH2:15][CH2:14][O:13]2)[N:6]=1)([CH3:4])([CH3:2])[CH3:3]

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 806044-MethylcyclohexylamineHCID 22150897HCID 22150897, compoundHCID 66643360HCID 66643360, compound

Product 1

HCID 25261851HCID 25261851, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
50 °C

Procedure

To a solution of Example 67C (33 mg, 0.14 mmol) in tetrahydrofuran (0.3 mL), was added triethylamine (28 mg, 0.27 mmol). After shaking a solution of p-nitrophenyl carbamoyl chloride (28 mg, 0.14 mmol) was added in tetrahydrofuran (0.3 mL). A precipitate was formed and after shaking for 30 minutes a solution of 4-methylcyclohexanamine (21 mg, 0.19 mmol) in tetrahydrofuran (0.6 mL) was added. The mixture was heated to 50° C. overnight. The mixture was cooled to ambient temperature, and filtered through Si-Carbonate cartridge, washed with methanol checked by LC/MS and concentrated to dryness. The residue was dissolved in 1:1 DMSO/Methanol and purified by preparative HPLC on a Phenomenex Luna C8(2) 5 μm 100 Å AXIA column (30 mm×75 mm). A gradient of acetonitrile (A) and 0.1% trifluoroacetic acid in water (B) was used, at a flow rate of 50 mL/min (0-0.5 min 10% A, 0.5-6.0 min linear gradient 10-100% A, 6.0-7.0 min 100% A, 7.0-8.0 min linear gradient 100-10% A) to afford the title compound. 1H NMR (500 MHz, DMSO/D2O) δ ppm 0.83-0.93 (m, 3H), 0.93-1.01 (m, 1H), 1.15-1.25 (m, 1H), 1.26-1.35 (m, 10H), 1.41-1.99 (m, 10H), 3.59-3.67 (m, 2H), 3.75-3.80 (m, 1H), 3.96-4.08 (m, 1H), 4.19-4.32 (m, 2H); MS (ESI) m/z 381 (M+H)+.

Workup

  1. customA precipitate was formed
  2. additionwas added
  3. temperatureThe mixture was cooled to ambient temperature
  4. filtrationfiltered through Si-Carbonate cartridge
  5. washwashed with methanol
  6. concentrationconcentrated to dryness
  7. dissolutionThe residue was dissolved in 1:1 DMSO/Methanol
  8. custompurified by preparative HPLC on a Phenomenex Luna C8(2) 5 μm 100 Å AXIA column (30 mm×75 mm)
  9. customwas used, at a flow rate of 50 mL/min (0-0.5 min 10% A, 0.5-6.0 min linear gradient 10-100% A, 6.0-7.0 min 100% A, 7.0-8.0 min linear gradient 100-10% A)

Sources & evidence

ORD record
ord-9d4493215f754d11a7db043f61a8e52e
Source dataset
uspto-grants-2015_11
Patent number
US09193713B2

Reaction notes

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