Hydrochloric Acid → HCID 86296962, compound

HRID 1773689Notes

Reaction equation

HRID 1773689 reaction equation
Br[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][N:3]=1.C([Li])CCC.[Cl:13][C:14]1[CH:15]=[CH:16][C:17]([C:20]([C:22]2[C:30]3[N:29]=[C:28]([O:31]CC)[N:27](C(OC(C)(C)C)=O)[C:26]=3[CH:25]=[C:24]([C:41]3[C:42]([CH3:47])=[N:43][O:44][C:45]=3[CH3:46])[CH:23]=2)=[O:21])=[N:18][CH:19]=1.Cl>O1CCCC1.C(O)C>[Cl:13][C:14]1[CH:15]=[CH:16][C:17]([C:20]([OH:21])([C:2]2[CH:7]=[CH:6][CH:5]=[CH:4][N:3]=2)[C:22]2[C:30]3[NH:29][C:28](=[O:31])[NH:27][C:26]=3[CH:25]=[C:24]([C:41]3[C:42]([CH3:47])=[N:43][O:44][C:45]=3[CH3:46])[CH:23]=2)=[N:18][CH:19]=1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 79732-BromopyridineHCID 117602053HCID 117602053, compoundHCID 178418339Butyllithium

Product 1

HCID 86296962HCID 86296962, compound

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
70 °C

Procedure

To 2-bromopyridine (0.02 ml, 0.2 mmol) in tetrahydrofuran (4 mL) at −78° C. was added n-butyllithium (0.15 mL, 0.24 mmol, 1.6 M in hexanes). After 30 minutes, tert-butyl 4-(5-chloropicolinoyl)-6-(3,5-dimethylisoxazol-4-yl)-2-ethoxy-1H-benzo[d]imidazole-1-carboxylate (33 mg, 0.07 mmol) in tetrahydrofuran (1 mL) was added drop-wise to the reaction. After 30 minutes, the reaction was warmed, quenched with saturated NH4Cl(aq) (10 mL), extracted with ethyl acetate (3×10 mL), dried over Na2SO4, and concentrated in vacuo. To the crude residue in ethanol (3 mL) was added hydrochloric acid (0.17 mL, 0.66 mmol, 4 M in 1,4-dioxane) and the mixture was heated to 70° C. in a microwave reactor for 45 minutes. Purification by reverse-phase HPLC (23-40% acetonitrile/water with 0.01% trifluoroacetic acid, Gemini C18 5μ) afforded 4-((5-chloropyridin-2-yl)(hydroxy)(pyridin-2-yl)methyl)-6-(3,5-dimethylisoxazol-4-yl)-1H-benzo[d]imidazol-2(3H)-one as an off-white solid.

Workup

  1. customto the reaction
  2. waitAfter 30 minutes
  3. temperaturethe reaction was warmed
  4. customquenched with saturated NH4Cl(aq) (10 mL)
  5. extractionextracted with ethyl acetate (3×10 mL)
  6. dry with materialdried over Na2SO4
  7. concentrationconcentrated in vacuo
  8. customPurification by reverse-phase HPLC (23-40% acetonitrile/water with 0.01% trifluoroacetic acid, Gemini C18 5μ)

Sources & evidence

ORD record
ord-33b73482559d472baf9ff5760f534e65
Source dataset
uspto-grants-2016_02
Patent number
US09255089B2

Reaction notes

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