Diisopropylethylamine → HCID 86719564, compound

HRID 2208812Notes

Reaction equation

HRID 2208812 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:11][CH:10]([C:12]2[CH:13]=[C:14]([N:22]([CH2:29][CH3:30])[CH:23]3[CH2:28][CH2:27][O:26][CH2:25][CH2:24]3)[C:15]([CH3:21])=[C:16]([CH:20]=2)[C:17]([OH:19])=O)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[NH2:64][CH2:65][C:66]1[C:67](=[O:74])[NH:68][C:69]([CH3:73])=[CH:70][C:71]=1[CH3:72]>CN(C=O)C.O>[CH3:72][C:71]1[CH:70]=[C:69]([CH3:73])[NH:68][C:67](=[O:74])[C:66]=1[CH2:65][NH:64][C:17]([C:16]1[CH:20]=[C:12]([CH:10]2[CH2:11][N:8]([C:6]([O:5][C:1]([CH3:2])([CH3:3])[CH3:4])=[O:7])[CH2:9]2)[CH:13]=[C:14]([N:22]([CH2:29][CH3:30])[CH:23]2[CH2:24][CH2:25][O:26][CH2:27][CH2:28]2)[C:15]=1[CH3:21])=[O:19]

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 70638443-(Aminomethyl)-4,6-dimethyl-1,2-dihydropyridin-2-oneHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 70873984HCID 70873984, compound

Product 1

HCID 86719564HCID 86719564, compoundYield 40.4%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a stirred solution of 5-{1-[(tert-butoxy)carbonyl]azetidin-3-yl}-3-[ethyl(oxan-4-yl)amino]-2-methylbenzoic acid (54 mg, 0.13 mmol) in DMF (2 ml) and the reaction was cooled using an ice bath followed by the addition of DIPEA (45 μl, 0.26 mmol) and HATU (59 mg, 0.15 mmol)). The reaction was stirred at 0° C. for 5 min after which time 3-(aminomethyl)-4,6-dimethyl-1,2-dihydropyridin-2-one (89%, 24 mg, 0.14 mmol) was added and the reaction was warmed room temperature for 16 h. The reaction mixture was then poured onto 50 ml of water and the aqueous phase was extracted with EtOAc (3×50 ml), washed with brine (50 ml) dried (Na2SO4), filtered and evaporated to give an oil. The product was then purified using a 5 g silica Isolute column eluting with 0% to 2.5% MeOH in DCM and evaporated to afford tert-butyl 3-(3-{[(4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl]carbamoyl}-5-[ethyl(oxan-4-yl)amino]-4-methylphenyl)azetidine-1-carboxylate as a colourless oil (29 mg). LC-MS 90%, m/z=553.3. This material was dissolved in 4M HCl in dioxane solution (3 ml) and stirred at room temperature for 90 min after which the solvent was evaporated to dryness and the compound purified by preparative HPLC to afford the title compound as a white solid (11 mg, 8% over 2 steps). LC-MS 97%, 2.17 min (7 minute LC-MS method), m/z=453.2, 1H NMR (500 MHz, MeOD) δ 7.26 (s, 1H), 7.18 (s, 1H), 6.14 (s, 1H), 4.48 (s, 2H), 4.39 (s, 2H), 4.22 (s, 3H), 3.93 (d, J=10.5 Hz, 2H), 3.40-3.33 (m, 2H), 3.29-2.90 (m, 3H), 2.40 (s, 3H), 2.31 (s, 3H), 2.26 (s, 3H), 1.68 (d, J=26.3 Hz, 4H), 0.87 (s, 3H).

Workup

  1. additionwas added
  2. extractionthe aqueous phase was extracted with EtOAc (3×50 ml)
  3. washwashed with brine (50 ml)
  4. dry with materialdried (Na2SO4)
  5. filtrationfiltered
  6. customevaporated
  7. customto give an oil
  8. customThe product was then purified
  9. washeluting with 0% to 2.5% MeOH in DCM
  10. customevaporated

Sources & evidence

ORD record
ord-586ed79de30440c685ce2a6ad4e14d30
Source dataset
uspto-grants-2016_06
Patent number
US09376422B2

Reaction notes

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