Water → HCID 178501910, compound

HRID 1488063Notes

Reaction equation

HRID 1488063 reaction equation
[NH:1]1[CH2:4][CH:3]([C:5]2[NH:6][C:7]([C:11]3[CH:12]=[C:13]([CH:28]=[CH:29][C:30]=3[CH3:31])[C:14]([N:16]3[CH2:19][CH:18]([C:20]4[CH:27]=[CH:26][C:23]([C:24]#[N:25])=[CH:22][CH:21]=4)[CH2:17]3)=[O:15])=[C:8]([CH3:10])[N:9]=2)[CH2:2]1.Cl[C:33]([O:35][CH3:36])=[O:34].C(N(CC)CC)C.O>CN(C)C=O.CC#N>[C:24]([C:23]1[CH:26]=[CH:27][C:20]([CH:18]2[CH2:17][N:16]([C:14]([C:13]3[CH:28]=[CH:29][C:30]([CH3:31])=[C:11]([C:7]4[NH:6][C:5]([CH:3]5[CH2:4][N:1]([C:33]([O:35][CH3:36])=[O:34])[CH2:2]5)=[N:9][C:8]=4[CH3:10])[CH:12]=3)=[O:15])[CH2:19]2)=[CH:21][CH:22]=1)#[N:25]

Participants

7

Reactant 4

HCID 962WaterHCID 6586Methyl chloroformateHCID 8471TriethylamineHCID 178425788HCID 178425788, compound2×

Product 1

HCID 178501910HCID 178501910, compoundYield 19.1%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6342AcetonitrileSolvent2×

Procedure

Into a 25-mL round-bottom flask, was placed a solution of 4-(1-(3-(2-(azetidin-3-yl)-4-methyl-1H-imidazol-5-yl)-4-methylbenzoyl)azetidin-3-yl)benzonitrile (compound 189.2, 100 mg, 0.24 mmol) in N,N-dimethylformamide (2 mL). Methyl chloroformate (33 μL, 0.42 mmol) and triethylamine (34 μL, 0.25 mmol) were added to the reaction. The reaction mixture was stirred for 2 h at room temperature, then was quenched with 10 mL of water. The aqueous phase was extracted with 3×5 mL of ethyl acetate. The combined organic layers were washed with 3×3 mL of brine and concentrated under reduced pressure. The residue was purified by silica gel chromatography with dichloromethane/methanol (10:1). The crude product (100 mg) was purified by Prep-HPLC with the following conditions (Prep-HPLC-020): Column, SunFire Prep C18 OBD Column, 5 μm, 19*150 mm; mobile phase, Water with 50 mmol NH4HCO3 and MeCN (33.0% MeCN up to 45.0% in 7 min, up to 100.0% in 2 min, down to 33.0% in 1 min); Detector, Waters 2489, 254 and 220 nm. This resulted in 21.5 mg (19%) of the title compound as a white solid. m/z (ES+) 470 (M+H)+.

Workup

  1. customInto a 25-mL round-bottom flask, was placed
  2. customwas quenched with 10 mL of water
  3. extractionThe aqueous phase was extracted with 3×5 mL of ethyl acetate
  4. washThe combined organic layers were washed with 3×3 mL of brine
  5. concentrationconcentrated under reduced pressure
  6. customThe residue was purified by silica gel chromatography with dichloromethane/methanol (10:1)
  7. customThe crude product (100 mg) was purified by Prep-HPLC with the following conditions (Prep-HPLC-020)
  8. waitup to 100.0% in 2 min
  9. waitdown to 33.0% in 1 min)

Sources & evidence

ORD record
ord-af65b68028614bcf9a4eeec3fde6a80b
Source dataset
uspto-grants-2016_08
Patent number
US09428502B2

Reaction notes

Loading…