Water → (3R)-N-[4'-({[(3-Methoxyphenyl)amino]carbonyl}amino)biphenyl-4-yl]quinuclidine-3-carboxamide hydrochloride

HRID 1661156Notes

Reaction equation

HRID 1661156 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]([N:9]=[C:10]=[O:11])[CH:6]=[CH:7][CH:8]=1.C(N(CC)CC)C.[ClH:19].Cl.[NH2:21][C:22]1[CH:27]=[CH:26][C:25]([C:28]2[CH:33]=[CH:32][C:31]([NH:34][C:35]([C@@H:37]3[CH:42]4[CH2:43][CH2:44][N:39]([CH2:40][CH2:41]4)[CH2:38]3)=[O:36])=[CH:30][CH:29]=2)=[CH:24][CH:23]=1.O>CN(C=O)C>[ClH:19].[CH3:1][O:2][C:3]1[CH:4]=[C:5]([NH:9][C:10]([NH:21][C:22]2[CH:27]=[CH:26][C:25]([C:28]3[CH:29]=[CH:30][C:31]([NH:34][C:35]([C@@H:37]4[CH:42]5[CH2:41][CH2:40][N:39]([CH2:44][CH2:43]5)[CH2:38]4)=[O:36])=[CH:32][CH:33]=3)=[CH:24][CH:23]=2)=[O:11])[CH:6]=[CH:7][CH:8]=1

Participants

6

Reactant 4

HCID 962WaterHCID 8471TriethylamineHCID 878433-Methoxyphenyl isocyanateHCID 67427707(3R)-N-(4'-Aminobiphenyl-4-yl)quinuclidine-3-carboxamide dihydrochloride

Product 1

HCID 11318130(3R)-N-[4'-({[(3-Methoxyphenyl)amino]carbonyl}amino)biphenyl-4-yl]quinuclidine-3-carboxamide hydrochloride

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

45.4 mg (0.30 mmol) of 3-methoxyphenyl isocyanate and 84.8 μl (0.61 mmol) of triethylamine are added to a solution of 60 mg (0.15 mmol) of ((3R)—N-(4′-aminobiphenyl-4-yl)quinuclidine-3-carboxamide dihydrochloride (Example 7A) in 0.5 ml of DMF. After 18 h at room temperature, 5 ml of water are added to the reaction mixture. The resulting precipitate is filtered off with suction, washed with water and dried under high vacuum. A preparative HPLC is carried out for further purification. The product fractions are concentrated, mixed with 3 ml of 1 N hydrochloric acid, again concentrated and dried under high vacuum. 22 mg (27.6% of theory) of the title compound are obtained.

Workup

  1. filtrationThe resulting precipitate is filtered off with suction
  2. washwashed with water
  3. customdried under high vacuum
  4. customA preparative HPLC is carried out for further purification
  5. concentrationThe product fractions are concentrated
  6. additionmixed with 3 ml of 1 N hydrochloric acid
  7. concentrationagain concentrated
  8. customdried under high vacuum

Sources & evidence

ORD record
ord-487ea740fcd54679a73263a45ed2439f
Source dataset
uspto-grants-2011_10
Patent number
US08030329B2

Reaction notes

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