Triethylamine → HCID 70873647, compound

HRID 2208944Notes

Reaction equation

HRID 2208944 reaction equation
[CH2:1]([N:3]([CH:14]1[CH2:19][CH2:18][C:17]([O:21][CH3:22])([CH3:20])[CH2:16][CH2:15]1)[C:4]1[C:5]([CH3:13])=[C:6]([CH:10]=[CH:11][CH:12]=1)[C:7]([O-])=[O:8])[CH3:2].[OH-].[Na+].[NH2:25][CH2:26][C:27]1[C:28](=[O:35])[NH:29][C:30]([CH3:34])=[CH:31][C:32]=1[CH3:33].C1CN([P+](ON2N=NC3C=CC=CC2=3)(N2CCCC2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F.C(N(CC)CC)C>C(O)C.O.CS(C)=O>[CH3:33][C:32]1[CH:31]=[C:30]([CH3:34])[NH:29][C:28](=[O:35])[C:27]=1[CH2:26][NH:25][C:7](=[O:8])[C:6]1[CH:10]=[CH:11][CH:12]=[C:4]([N:3]([CH2:1][CH3:2])[CH:14]2[CH2:19][CH2:18][C:17]([O:21][CH3:22])([CH3:20])[CH2:16][CH2:15]2)[C:5]=1[CH3:13]

Participants

9

Reactant 5

HCID 8471TriethylamineHCID 14798Sodium HydroxideHCID 2724699PyBOPHCID 70638443-(Aminomethyl)-4,6-dimethyl-1,2-dihydropyridin-2-oneHCID 131735972HCID 131735972, compound

Product 1

HCID 70873647HCID 70873647, compound

Reagents, catalysts & solvents 3

HCID 679Dimethyl SulfoxideSolventHCID 702EthanolSolventHCID 962WaterSolvent2×

Conditions

Temperature
70 °C

Procedure

A mixture of 3-(ethyl(4-methoxy-4-methylcyclohexyl)amino)-2-methylbenzoate (300 mg, 0.94 mmol) and NaOH (56 mg, 1.41 mmol) in 5 ml of ethanol and water (4:1) was heated at 70° C. for 2 h. The reaction mixture was concentrated to dryness and the crude material was partitioned between water and ethyl acetate. The organic layer was dried over Na2SO4, and concentrated under reduced pressure to afford 280 mg of the crude acid. A mixture of the crude acid (280 mg, 0.91 mmol), 3-(aminomethyl)-4,6-dimethylpyridin-2(1H)-one (279 mg, 1.83 mmol), PyBOP (716 mg, 1.37 mmol) and triethylamine (0.12 ml, 0.91 mmol) in DMSO (3 ml) was stirred at room temperature overnight. The reaction mixture was diluted with water, extracted with 10% MeOH in DCM, dried over Na2SO4, and concentrated to a residue which was purified by silica gel column chromatography to afford the title compound N-((4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-3-(ethyl(4-methoxy-4-methylcyclohexyl)amino)-2-methylbenzamide as a mixture of isomers (70 mg, 17%). LCMS: 440.45 (M+1)+; HPLC: 45.77 & 48.47% (@ 210-370 nm) (Rt; 4.297 & 4.430; Method: Column: YMC ODS-A 150 mm×4.6 mm×5μ; Mobile Phase: A; 0.05% TFA in water/B; 0.05% TFA in acetonitrile; Inj. Vol: 10 μL, Col. Temp.: 30° C.; Flow rate: 1.4 mL/min.; Gradient: 5% B to 95% B in 8 min, Hold for 1.5 min, 9.51-12 min 5% B); 1H NMR (DMSO-d6, 400 MHz) δ 11.45 (s, 1H), 8.03 (bs, 1H), 7.15 (bs, 2H), 6.91 (s, 1H), 5.85 (s, 1H), 4.25 (d, 2H, J=2.8 Hz), 3.10-2.90 (m, 7H), 2.19 (s, 6H), 2.10 (s, 3H), 1.72-1.10 (m, 8H), 1.08 & 0.99 (s, 3H), 0.77 (t, 3H).

Workup

  1. concentrationThe reaction mixture was concentrated to dryness
  2. customthe crude material was partitioned between water and ethyl acetate
  3. dry with materialThe organic layer was dried over Na2SO4
  4. concentrationconcentrated under reduced pressure
  5. customto afford 280 mg of the crude acid
  6. extractionextracted with 10% MeOH in DCM
  7. dry with materialdried over Na2SO4
  8. concentrationconcentrated to a residue which
  9. customwas purified by silica gel column chromatography

Sources & evidence

ORD record
ord-cb821d8377374cf78cd906ae77a84f4e
Source dataset
uspto-grants-2016_06
Patent number
US09376422B2

Reaction notes

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