Water → HCID 178432708, compound

HRID 1487872Notes

Reaction equation

HRID 1487872 reaction equation
[CH3:1][C:2]1[NH:3][C:4]([C:8]2[CH:9]=[C:10]([CH:27]=[CH:28][C:29]=2F)[C:11]([N:13]2[CH2:18][CH2:17][CH:16]([C:19]3[CH:26]=[CH:25][C:22]([C:23]#[N:24])=[CH:21][CH:20]=3)[CH2:15][CH2:14]2)=[O:12])=[C:5]([CH3:7])[N:6]=1.Cl.[NH:32]1[CH2:35][CH2:34][CH2:33]1.C(=O)([O-])[O-].[Cs+].[Cs+].O>O1CCOCC1.CC#N>[N:32]1([C:29]2[CH:28]=[CH:27][C:10]([C:11]([N:13]3[CH2:14][CH2:15][CH:16]([C:19]4[CH:26]=[CH:25][C:22]([C:23]#[N:24])=[CH:21][CH:20]=4)[CH2:17][CH2:18]3)=[O:12])=[CH:9][C:8]=2[C:4]2[NH:3][C:2]([CH3:1])=[N:6][C:5]=2[CH3:7])[CH2:35][CH2:34][CH2:33]1

Participants

7

Reactant 4

HCID 962WaterHCID 10796Cesium carbonateHCID 12308726Azetidine hydrochlorideHCID 178432707HCID 178432707, compound2×

Product 1

HCID 178432708HCID 178432708, compoundYield 27.1%

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolvent2×HCID 312751,4-DioxaneSolvent

Conditions

Temperature
120 °C

Procedure

Into a 10-mL sealed tube, was placed a solution of 4-(1-(3-(2,4-dimethyl-1H-imidazol-5-yl)-4-fluorobenzoyl)piperidin-4-yl)benzonitrile (compound 25.1, 200 mg, 0.50 mmol) in 1,4-dioxane (4 mL). Azetidine hydrochloride (50 mg, 0.53 mmol) and cesium carbonate (500 mg, 1.53 mmol) were added and the mixture was stirred for 48 h at 120° C. behind a blast shield. The mixture was cooled and the solids were removed by filtration. The filtrate was concentrated under reduced pressure and the crude product was purified by Prep-HPLC with the following conditions (1#-Pre-HPLC-001(SHIMADZU)): Column, SunFire Prep C18 OBD Column, 5 um, 19*150 mm; mobile phase, Water with 50 mmol NH4HCO3 and CH3CN (33.0% CH3CN up to 46.0% in 10 min, up to 100.0% in 3 min, down to 33.0% in 1 min); Detector, Waters 2489, 254 & 220 nm. The fractions containing pure compound were combined and lyophilized to yield 59.6 mg (27%) of the title compound as a white solid m/z (ES+) 440 (M+H)+.

Workup

  1. customInto a 10-mL sealed tube
  2. temperatureThe mixture was cooled
  3. customthe solids were removed by filtration
  4. concentrationThe filtrate was concentrated under reduced pressure
  5. customthe crude product was purified by Prep-HPLC with the following conditions (1#-Pre-HPLC-001(SHIMADZU))
  6. waitup to 100.0% in 3 min
  7. waitdown to 33.0% in 1 min)
  8. additionThe fractions containing pure compound

Sources & evidence

ORD record
ord-be36e7fdd5d34255b6d6aa7582c1ff19
Source dataset
uspto-grants-2016_08
Patent number
US09428502B2

Reaction notes

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