Potassium Carbonate → (3R)-N-(4'-[(Isopropylamino)sulfonyl]biphenyl-4-yl)quinuclidine-3-carboxamide hydrochloride

HRID 899184Notes

Reaction equation

HRID 899184 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]([S:32]([NH:35][CH:36]([CH3:38])[CH3:37])(=[O:34])=[O:33])=[CH:28][CH:27]=2)=[CH:22][CH:21]=1.O1CCOCC1>CN(C=O)C>[ClH:18].[CH:36]([NH:35][S:32]([C:29]1[CH:30]=[CH:31][C:26]([C:23]2[CH:22]=[CH:21][C:20]([NH:19][C:16]([C@@H:10]3[CH:11]4[CH2:14][CH2:15][N:8]([CH2:13][CH2:12]4)[CH2:9]3)=[O:17])=[CH:25][CH:24]=2)=[CH:27][CH:28]=1)(=[O:34])=[O:33])([CH3:38])[CH3:37]

Participants

6

Reactant 4

HCID 11430Potassium CarbonateHCID 312751,4-DioxaneHCID 57462844(3R)-Quinuclidine-3-carbonyl chloride hydrochlorideHCID 596940904'-Amino-N-isopropylbiphenyl-4-sulfonamide

Product 1

HCID 11374690(3R)-N-(4'-[(Isopropylamino)sulfonyl]biphenyl-4-yl)quinuclidine-3-carboxamide hydrochloride

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

64.3 mg (0.46 mmol) of potassium carbonate are added to a mixture, prepared under argon, of 65.1 mg (0.31 mmol) of (3R)-quinuclidine-3-carbonyl chloride hydrochloride (Example 5A) and 45.0 mg (0.15 mmol) of 4′-amino-N-isopropylbiphenyl-4-sulfonamide (Example 12A) in 2.2 ml of a 10:1 mixture of dioxane and DMF. After 18 h at 100° C., the reaction mixture is concentrated in vacuo. The residue is dissolved in water and acetonitrile and purified by preparative HPLC. The product fractions are concentrated, mixed with 5 ml of a 2:1 mixture of acetonitrile and 1 N hydrochloric acid, again concentrated and dried under high vacuum. 21 mg (29.2% of theory) of the title compound are obtained.

Workup

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

Sources & evidence

ORD record
ord-846dfce475974ed4b47dda195b6727fe
Source dataset
uspto-grants-2008_04
Patent number
US07354930B2

Reaction notes

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