Potassium Carbonate → [(4'-{[(3R)-1-Azabicyclo[2.2.2]oct-3-ylcarbonyl]amino}biphenyl-4-yl)amino](oxo)acetic acid hydrochloride

HRID 588343Notes

Reaction equation

HRID 588343 reaction equation
C(=O)([O-])[O-].[K+].[K+].Cl.[N:8]12[CH2:15][CH2:14][CH:11]([CH2:12][CH2:13]1)[C@@H:10]([C:16]([Cl:18])=[O:17])[CH2:9]2.[NH2:19][C:20]1[CH:25]=[CH:24][C:23]([C:26]2[CH:31]=[CH:30][C:29]([NH:32][C:33](=[O:37])[C:34]([OH:36])=[O:35])=[CH:28][CH:27]=2)=[CH:22][CH:21]=1.O1CCOCC1>CN(C=O)C>[ClH:18].[N:8]12[CH2:15][CH2:14][CH:11]([CH2:12][CH2:13]1)[C@@H:10]([C:16]([NH:19][C:20]1[CH:21]=[CH:22][C:23]([C:26]3[CH:31]=[CH:30][C:29]([NH:32][C:33](=[O:37])[C:34]([OH:36])=[O:35])=[CH:28][CH:27]=3)=[CH:24][CH:25]=1)=[O:17])[CH2:9]2

Participants

6

Reactant 4

HCID 11430Potassium CarbonateHCID 312751,4-DioxaneHCID 293247[(4'-Aminobiphenyl-4-yl)amino](oxo)acetic acidHCID 57462844(3R)-Quinuclidine-3-carbonyl chloride hydrochloride

Product 1

HCID 11453179[(4'-{[(3R)-1-Azabicyclo[2.2.2]oct-3-ylcarbonyl]amino}biphenyl-4-yl)amino](oxo)acetic acid hydrochloride

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

300 mg (2.14 mmol) of potassium carbonate are added to a mixture, prepared under argon, of 300 mg (1.43 mmol) of (3R)-quinuclidine-3-carbonyl chloride hydrochloride (Example 5A) and 180 mg (0.71 mmol) of [(4′-aminobiphenyl-4-yl)amino](oxo)acetic acid [CAS Registry No. 100872-66-0] in 11 ml of a 10:1 mixture of dioxane and DMF. After 18 h at 100° C., the reaction mixture is concentrated in vacuo, and the residue is dissolved in water and acetonitrile and purified by preparative HPLC. The concentrated product fractions are mixed with 5 ml of a 2:1 mixture of acetonitrile and 1 N hydrochloric acid and again concentrated. Drying under high vacuum results in 64 mg (20.3% of theory) of the title compound.

Workup

  1. concentrationthe reaction mixture is concentrated in vacuo
  2. dissolutionthe residue is dissolved in water
  3. customacetonitrile and purified by preparative HPLC
  4. additionThe concentrated product fractions are mixed with 5 ml of a 2:1 mixture of acetonitrile and 1 N hydrochloric acid
  5. concentrationagain concentrated
  6. customDrying under high vacuum

Sources & evidence

ORD record
ord-88a9f0a27f29438ab59333498b44a76a
Source dataset
uspto-grants-2016_01
Patent number
US09227964B2

Reaction notes

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