Acetic Acid → HCID 178433958, compound

HRID 1487849Notes

Reaction equation

HRID 1487849 reaction equation
[C:1]([C:3]1[CH:8]=[CH:7][C:6]([CH:9]2[CH2:12][N:11]([C:13]([C:15]3[C:16]([CH3:28])=[CH:17][C:18]([CH:24]4[CH2:27][CH2:26][CH2:25]4)=[C:19]([CH:23]=3)[C:20]([NH2:22])=O)=[O:14])[CH2:10]2)=[CH:5][CH:4]=1)#[N:2].CO[C:31](OC)([N:33](C)C)[CH3:32].C(O)(=O)C.O.[NH2:43]N>C(Cl)Cl.O1CCOCC1>[CH:24]1([C:18]2[C:19]([C:20]3[NH:33][C:31]([CH3:32])=[N:43][N:22]=3)=[CH:23][C:15]([C:13]([N:11]3[CH2:12][CH:9]([C:6]4[CH:7]=[CH:8][C:3]([C:1]#[N:2])=[CH:4][CH:5]=4)[CH2:10]3)=[O:14])=[C:16]([CH3:28])[CH:17]=2)[CH2:27][CH2:26][CH2:25]1

Participants

7

Reactant 4

HCID 176Acetic AcidHCID 24654Hydrazine hydrate (1:1)HCID 878351,1-Dimethoxyethyl(dimethyl)amineHCID 900211065-(3-(4-Cyanophenyl)azetidine-1-carbonyl)-2-cyclobutyl-4-methylbenzamide2×

Product 1

HCID 178433958HCID 178433958, compoundYield 43.7%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
90 °C

Procedure

To a 4-mL vial was added 5-(3-(4-cyanophenyl)azetidine-1-carbonyl)-2-cyclobutyl-4-methylbenzamide (compound 6, 39 mg, 0.104 mmol), dioxane (200 μL) and 1,1-dimethoxy-N,N-dimethylethanamine (76 μL, 0.52 mmol). The mixture was heated at 90° C. for 3 hours then cooled to room temperature. Acetic acid (42 μL, 0.73 mmol) and hydrazine hydrate (30 μL, 0.62 mmol) were added and the mixture was stirred at 90° C. for 1 hour. The mixture was diluted with DCM (5 mL) and washed with aqueous NaH2PO4 (1M, 5 mL) then saturated aqueous NaHCO3 (5 mL). The organics was dried (Na2SO4), filtered, and concentrated under reduced pressure. The residue was purified by silica gel preparative thin layer chromatography (DCM/8% MeOH) to yield the title compound as a white powder (18.7 mg, 43%). m/z (ES+) 412 (M+H)+. 1H NMR (400 MHz, CD3OD): δ 7.65 (d with fine str., J=8.4 Hz, 2H), 7.57 (s, 1H), 7.39 (d with fine str., J=8.4 Hz, 2H), 7.29 (s, 1H), 4.61 (app t, J=9.6 Hz, 1H), 4.39 (app t, J=8.8 Hz, 1H), 4.27-4.18 (m, 1H), 4.17-4.07 (m, 1H), 4.02-3.94 (m, 1H), 3.94-3.84 (m, 1H), 2.50 (s, 3H), 2.48 (s, 3H), 2.25-2.11 (m, 2H), 2.11-1.88 (m, 3H), 1.82-1.71 (m, 1H).

Workup

  1. temperaturethen cooled to room temperature
  2. washwashed with aqueous NaH2PO4 (1M, 5 mL)
  3. dry with materialThe organics was dried (Na2SO4)
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customThe residue was purified by silica gel preparative thin layer chromatography (DCM/8% MeOH)

Sources & evidence

ORD record
ord-732521c12af441569b3123c65695be82
Source dataset
uspto-grants-2016_08
Patent number
US09428502B2

Reaction notes

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