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

HRID 2362757ノート

反応式

HRID 2362757 の反応式
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

参加物

6

反応物 4

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

生成物 1

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

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

実験手順

300 mg (2.14 mmol) of potassium carbonate are added to a mixture, prepared wider 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. HPLC (Method 1): Rt=3.40 min. MS (ESIpos): m/z=350 (M+H)+.

後処理

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

出典と根拠

ORDレコード
ord-fe2195f3379740fb8e6d0b7f3abae13a
出典データセット
uspto-grants-2014_04
特許番号
US08691840B2

反応ノート

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