Methanesulfonic Acid → HCID 68288980, compound

HRID 541380Notes

Reaction equation

HRID 541380 reaction equation
[C:1]([C:3]1[CH:8]=[CH:7][C:6]([CH:9]2[CH2:14][CH2:13][N:12]([C:15]([C:17]3[C:18]([CH3:31])=[CH:19][C:20]([CH:27]4[CH2:30][CH2:29][CH2:28]4)=[C:21]([CH:26]=3)[C:22]([NH:24][NH2:25])=[O:23])=[O:16])[CH2:11][CH2:10]2)=[CH:5][CH:4]=1)#[N:2].CS(O)(=O)=O.C(O[C:40](OCC)(OCC)[CH2:41][CH3:42])C>O1CCOCC1.C(OCC)(=O)C>[CH:27]1([C:20]2[C:21]([C:22]3[O:23][C:40]([CH2:41][CH3:42])=[N:25][N:24]=3)=[CH:26][C:17]([C:15]([N:12]3[CH2:11][CH2:10][CH:9]([C:6]4[CH:5]=[CH:4][C:3]([C:1]#[N:2])=[CH:8][CH:7]=4)[CH2:14][CH2:13]3)=[O:16])=[C:18]([CH3:31])[CH:19]=2)[CH2:30][CH2:29][CH2:28]1

Participants

6

Reactant 3

HCID 6395Methanesulfonic AcidHCID 66995Ethyl orthopropionateHCID 68288791HCID 68288791, compound2×

Product 1

HCID 68288980HCID 68288980, compoundYield 79%

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
110 °C

Procedure

To a round-bottom flask was added a solution of 5-(4-(4-cyanophenyl)piperidine-1-carbonyl)-2-cyclobutyl-4-methylbenzohydrazide (compound 230.4, 150 mg, 0.360 mmol, 1.00 equiv) in dioxane (5 mL). MeSO3H (7 mg, 0.07 mmol, 0.20 equiv), and 1,1,1-triethoxypropane (190 mg, 1.08 mmol, 3.00 equiv) were added to the reaction. The resulting solution was stirred for 20 min at 110° C., then cooled to room temperature and diluted with 50 mL of ethyl acetate. The organic layer was washed with 2×20 mL of water, dried over anhydrous sodium sulfate and concentrated in vacuo. The crude product (200 mg) was purified by Prep-HPLC with the following conditions (1#-Pre-HPLC-001(SHIMADZU)): Column, SunFire Prep C18, 19*150 mm 5 um; mobile phase, water with 0.05% TFA and CH3CN (64.0% CH3CN up to 76.0% in 6 min, up to 100.0% in 4 min, down to 64.0% in 1 min); Detector, Waters 2489 254&220 nm. The fractions containing pure compound were combined and lyophilized to yield 129 mg (79%) of the title compound as a white solid. m/z (ES+) 455 (M+H)+. 1H-NMR (300 MHz, CD3OD, ppm): δ 7.73-7.67 (m, 3H), 7.52-7.48 (m, 3H), 5-4.94 (m, 1H), 4.25-4.20 (m, 1H), 3.60-3.58 (m, 1H), 3.33-3.24 (m, 1H), 3.05-2.97 (m, 4H), 2.49 and 2.30 (2 singlets, amide rotamers, CH3, 3H), 2.39-2.34 (m, 2H), 2.19-1.91 (m, 4H), 1.88-1.66 (m, 4H), 1.49-1.42 (t, 3H).

Workup

  1. temperaturecooled to room temperature
  2. washThe organic layer was washed with 2×20 mL of water
  3. dry with materialdried over anhydrous sodium sulfate
  4. concentrationconcentrated in vacuo
  5. customThe crude product (200 mg) was purified by Prep-HPLC with the following conditions (1#-Pre-HPLC-001(SHIMADZU))
  6. waitmobile phase, water with 0.05% TFA and CH3CN (64.0% CH3CN up to 76.0% in 6 min
  7. waitup to 100.0% in 4 min
  8. waitdown to 64.0% in 1 min)
  9. additionThe fractions containing pure compound

Sources & evidence

ORD record
ord-70ef60a85cfd40c3bd6cf8a09d344925
Source dataset
uspto-grants-2014_10
Patent number
US08871790B2

Reaction notes

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