Hydrochloric Acid → HCID 70874985, compound

HRID 2208827Notes

Reaction equation

HRID 2208827 reaction equation
[CH2:1]([N:3]([CH:20]1[CH2:25][CH2:24][O:23][CH2:22][CH2:21]1)[C:4]1[C:5]([CH3:19])=[C:6]([CH:11]=[C:12]([CH:14]2[CH2:17][N:16]([CH3:18])[CH2:15]2)[CH:13]=1)[C:7](OC)=[O:8])[CH3:2].[OH-].[Na+].Cl.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C.[NH2:62][CH2:63][C:64]1[C:65](=[O:72])[NH:66][C:67]([CH3:71])=[CH:68][C:69]=1[CH3:70]>C1COCC1.CN(C=O)C.CO>[CH3:70][C:69]1[CH:68]=[C:67]([CH3:71])[NH:66][C:65](=[O:72])[C:64]=1[CH2:63][NH:62][C:7](=[O:8])[C:6]1[CH:11]=[C:12]([CH:14]2[CH2:15][N:16]([CH3:18])[CH2:17]2)[CH:13]=[C:4]([N:3]([CH2:1][CH3:2])[CH:20]2[CH2:25][CH2:24][O:23][CH2:22][CH2:21]2)[C:5]=1[CH3:19]

Participants

10

Reactant 6

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 81531DiisopropylethylamineHCID 70638443-(Aminomethyl)-4,6-dimethyl-1,2-dihydropyridin-2-one2×HCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)2×HCID 70873860HCID 70873860, compound

Product 1

HCID 70874985HCID 70874985, compoundYield 20%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
50 °C

Procedure

Methyl 3-[ethyl(oxan-4-yl)amino]-2-methyl-5-(1-methylazetidin-3-yl)benzoate (103 mg, 0.30 mmol) was dissolved in THF (20 ml) and MeOH (5 ml) and 2M NaOH (1.49 ml, 2.97 mmol) was added. The reaction was stirred at 50° C. for 16 h, cooled, acidified to pH4 using 6M HCl and the solvent evaporated under reduced pressure, and the residue dried in a vacuum oven at 40° C. for 5 h to afford the crude acid. To the acid in DMF (10 ml) were added HATU (170 mg, 0.45 mmol) and DIPEA (130 μl, 0.74 mmol). The mixture was stirred at room temperature for 5 min and then 3-(aminomethyl)-4,6-dimethyl-1,2-dihydropyridin-2-one (89%, 66 mg, 0.39 mmol) was added. The reaction was stirred for 16 h after which additional HATU (80 mg) and 3-(aminomethyl)-4,6-dimethyl-1,2-dihydropyridin-2-one (30 mg) and the mixture stirred a further 5 h. The reaction mixture was poured onto distilled after (50 ml), extracted with EtOAc (3×50 ml), washed with brine (2×20 ml), dried with Na2SO4, filtered and evaporated. The crude residue was purified using preparative HPLC and evaporated to afford the title compound as an off-white solid (28 mg, 5% over three steps). LC-MS 95%, m/z=467.3, 1H NMR (500 MHz, Acetone-d6) δ 10.73 (s, 1H), 7.61 (s, 1H), 7.30 (s, 1H), 7.26 (s, 1H), 5.97 (s, 1H), 4.74 (t, J=9.9 Hz, 2H), 4.60 (t, J=9.6 Hz, 2H), 4.38 (q, J=6.2 Hz, 3H), 3.83 (d, J=11.6 Hz, 2H), 3.27 (s, 3H), 3.23 (t, J=11.6 Hz, 2H), 3.10 (dd, J=14.1, 7.0 Hz, 2H), 3.04-2.97 (m, 1H), 2.34 (s, 3H), 2.31 (s, 3H), 2.25 (s, 3H), 1.67 (d, J=11.1 Hz, 2H), 1.56 (td, J=11.8, 4.1 Hz, 2H), 0.83 (t, J=7.0 Hz, 3H).

Workup

  1. temperaturecooled
  2. customthe solvent evaporated under reduced pressure
  3. customthe residue dried in a vacuum oven at 40° C. for 5 h
  4. customto afford the crude acid
  5. stirringThe mixture was stirred at room temperature for 5 min
  6. stirringthe mixture stirred a further 5 h
  7. additionThe reaction mixture was poured
  8. distillationonto distilled after (50 ml)
  9. extractionextracted with EtOAc (3×50 ml)
  10. washwashed with brine (2×20 ml)
  11. dry with materialdried with Na2SO4
  12. filtrationfiltered
  13. customevaporated
  14. customThe crude residue was purified
  15. customevaporated

Sources & evidence

ORD record
ord-aab29b8dfbcd47969e95c7cdd4d61501
Source dataset
uspto-grants-2016_06
Patent number
US09376422B2

Reaction notes

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