Water → HCID 178473763, compound

HRID 1488062Notes

Reaction equation

HRID 1488062 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.C(N(CC)CC)C.[C:39](OC(=O)C)(=[O:41])[CH3:40].O>CN(C)C=O.CC#N>[C:39]([N: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[CH2:17][CH:18]([C:20]4[CH:27]=[CH:26][C:23]([C:24]#[N:25])=[CH:22][CH:21]=4)[CH2:19]3)=[O:15])=[C:8]([CH3:10])[N:9]=2)[CH2:2]1)(=[O:41])[CH3:40]

Participants

7

Reactant 4

HCID 962WaterHCID 7918Acetic AnhydrideHCID 8471TriethylamineHCID 178425788HCID 178425788, compound2×

Product 1

HCID 178473763HCID 178473763, compoundYield 38.1%

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, 80 mg, 0.19 mmol) in N,N-dimethylformamide (1 mL). Triethylamine (27 μL, 0.20 mmol) and acetic anhydride (19 μL, 0.20 mmol) were added to the reaction. The reaction mixture was stirred for 2 h at room temperature, then quenched with 10 mL of water. The aqueous phase was extracted with 3×3 mL of ethyl acetate and the combined organic extracts were concentrated under reduced pressure. 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 (28% MeCN up to 40% in 7 min, up to 100% in 2 min, down to 28% in 1 min); Detector, Waters 2489 255 and 220 nm. This resulted in 32.8 mg (37%) of the title compound a white solid. m/z (ES+) 454 (M+H)+.

Workup

  1. customInto a 25-mL round-bottom flask, was placed
  2. customquenched with 10 mL of water
  3. extractionThe aqueous phase was extracted with 3×3 mL of ethyl acetate
  4. concentrationthe combined organic extracts were concentrated under reduced pressure
  5. customThe crude product (100 mg) was purified by Prep-HPLC with the following conditions (Prep-HPLC-020)
  6. waitup to 100% in 2 min
  7. waitdown to 28% in 1 min)

Sources & evidence

ORD record
ord-9e1030a1b70542f882fe37646aa613f2
Source dataset
uspto-grants-2016_08
Patent number
US09428502B2

Reaction notes

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