1-Hydroxybenzotriazole → HCID 178494665, compound

HRID 1487824Notes

Reaction equation

HRID 1487824 reaction equation
[CH3:1][O:2][CH2:3][C:4]1[NH:5][C:6]([C:10]2[C:11]([CH3:20])=[CH:12][C:13]([CH3:19])=[C:14]([CH:18]=2)[C:15]([OH:17])=O)=[C:7]([CH3:9])[N:8]=1.CCN=C=NCCCN(C)C.Cl.C1C=CC2N(O)N=NC=2C=1.Cl.[NH:44]1[CH2:49][CH2:48][CH:47]([C:50]2[CH:57]=[CH:56][C:53]([C:54]#[N:55])=[CH:52][CH:51]=2)[CH2:46][CH2:45]1>CN(C)C1C=CN=CC=1.CN(C)C=O>[CH3:1][O:2][CH2:3][C:4]1[NH:5][C:6]([C:10]2[C:11]([CH3:20])=[CH:12][C:13]([CH3:19])=[C:14]([CH:18]=2)[C:15]([N:44]2[CH2:49][CH2:48][CH:47]([C:50]3[CH:57]=[CH:56][C:53]([C:54]#[N:55])=[CH:52][CH:51]=3)[CH2:46][CH2:45]2)=[O:17])=[C:7]([CH3:9])[N:8]=1

Participants

7

Reactant 4

HCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 193916184-(Piperidin-4-yl)benzonitrile--hydrogen chloride (1/1)2×HCID 178494666HCID 178494666, compound2×

Product 1

HCID 178494665HCID 178494665, compoundYield 35.4%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6228DimethylformamideSolvent

Procedure

A mixture of 5-(2-(methoxymethyl)-4-methyl-1H-imidazol-5-yl)-2,4-dimethylbenzoic acid (compound 2.3, 140 mg, 0.51 mmol), EDC.HCl (150 mg, 0.78 mmol), 4-dimethylaminopyridine (190 mg, 1.56 mmol), and HOBT (80 mg, 0.59 mmol) in N,N-dimethylformamide (6 mL). The mixture was stirred at room temperature, then after 15 min, 4-(piperidin-4-yl)benzonitrile hydrochloride (compound 1.2, 100 mg, 0.45 mmol) was added. The resulting solution was stirred for 15 h at room temperature, then quenched with 20 mL of H2O. The aqueous was extracted with ethyl acetate (40 mL) and the combined organics was washed with brine (2×30 mL), dried (Na2SO4), filtered, and concentrated under reduced pressure. The residue 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 0.05% TFA and CH3CN (23% CH3CN up to 38% in 7 min, up to 100% in 2 min, down to 23% in 1 min); Detector, Waters 2489, 254 &220 nm. The fractions containing pure compound were combined and lyophilized to yield the title compound as a white solid (70.4 mg, 35%).

Workup

  1. stirringThe resulting solution was stirred for 15 h at room temperature
  2. customquenched with 20 mL of H2O
  3. extractionThe aqueous was extracted with ethyl acetate (40 mL)
  4. washthe combined organics was washed with brine (2×30 mL)
  5. dry with materialdried (Na2SO4)
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe residue was purified by Prep-HPLC with the following conditions (1#-Pre-HPLC-001(SHIMADZU))
  9. waitmobile phase, water with 0.05% TFA and CH3CN (23% CH3CN up to 38% in 7 min
  10. waitup to 100% in 2 min
  11. waitdown to 23% in 1 min)
  12. additionThe fractions containing pure compound

Sources & evidence

ORD record
ord-a86d1a1e48b54d18ba6ec57d405da35c
Source dataset
uspto-grants-2016_08
Patent number
US09428502B2

Reaction notes

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