Water → HCID 178427988, compound

HRID 1488233Notes

Reaction equation

HRID 1488233 reaction equation
[CH3:1][C:2]1[C:6]([CH3:7])=[C:5]([C:8]2[C:9](F)=[CH:10][C:11]([CH3:28])=[C:12]([CH:27]=2)[C:13]([N:15]2[CH2:18][CH:17]([C:19]3[CH:26]=[CH:25][C:22]([C:23]#[N:24])=[CH:21][CH:20]=3)[CH2:16]2)=[O:14])[NH:4][N:3]=1.[NH:30]1[CH2:33][CH2:32][CH2:31]1.C([O-])([O-])=O.[Cs+].[Cs+].O>O1CCOCC1.CCOC(C)=O.CC#N>[N:30]1([C:9]2[C:8]([C:5]3[NH:4][N:3]=[C:2]([CH3:1])[C:6]=3[CH3:7])=[CH:27][C:12]([C:13]([N:15]3[CH2:16][CH:17]([C:19]4[CH:26]=[CH:25][C:22]([C:23]#[N:24])=[CH:21][CH:20]=4)[CH2:18]3)=[O:14])=[C:11]([CH3:28])[CH:10]=2)[CH2:33][CH2:32][CH2:31]1

Participants

8

Reactant 4

HCID 962WaterHCID 10422AzetidineHCID 10796Cesium carbonateHCID 178427818HCID 178427818, compound2×

Product 1

HCID 178427988HCID 178427988, compoundYield 43%

Reagents, catalysts & solvents 3

HCID 6342AcetonitrileSolvent2×HCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
120 °C

Procedure

Into a 5-mL sealed tube, was placed a solution of 4-(1-(5-(3,4-dimethyl-1H-pyrazol-5-yl)-4-fluoro-2-methylbenzoyl)azetidin-3-yl)benzonitrile (compound 377.2, 120 mg, 0.31 mmol) in dioxane (3 mL). Azetidine (833 μL, 12.4 mmol) and Cs2CO3 (1.01 g, 3.09 mmol) were added to the reaction. The reaction mixture was stirred for 20 h at 120° C., then cooled with a water/ice bath. The resulting solution was diluted with 30 mL of EtOAc. The organic layer was washed with 3×20 mL of brine, dried over anhydrous sodium sulfate and concentrated under reduced pressure. The crude product (200 mg) was purified by Prep-HPLC with the following conditions (Prep-HPLC-020): Column, SunFire Prep C18 OBD Column, 5 um, 19*100 mm; mobile phase, Water with 10 mmol NH4HCO3 and MeCN (36.0% MeCN up to 50.0% in 6 min, up to 95.0% in 2 min, down to 36.0% in 1 min); Detector, waters 2489 254 & 220 nm. This resulted in 56 mg (43%) of the title compound as a white solid. m/z (ES+) 426 (M+H)+.

Workup

  1. customInto a 5-mL sealed tube
  2. temperaturecooled with a water/ice bath
  3. washThe organic layer was washed with 3×20 mL of brine
  4. dry with materialdried over anhydrous sodium sulfate
  5. concentrationconcentrated under reduced pressure
  6. customThe crude product (200 mg) was purified by Prep-HPLC with the following conditions (Prep-HPLC-020)
  7. waitup to 95.0% in 2 min
  8. waitdown to 36.0% in 1 min)

Sources & evidence

ORD record
ord-092cb013e315483997652f0a8abeb012
Source dataset
uspto-grants-2016_08
Patent number
US09428502B2

Reaction notes

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