Diisopropylethylamine → 6-chloro-5-(4-chloro-phenyl)-N-((1R,2R)-2-hydroxy-cyclohexyl)-nicotinamide

HRID 505961ノート

反応式

HRID 505961 の反応式
[Cl:1][C:2]1[C:10]([C:11]2[CH:16]=[CH:15][C:14]([Cl:17])=[CH:13][CH:12]=2)=[CH:9][C:5]([C:6]([OH:8])=O)=[CH:4][N:3]=1.Cl.[NH2:19][C@@H:20]1[CH2:25][CH2:24][CH2:23][CH2:22][C@H:21]1[OH:26].CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.C(N(C(C)C)C(C)C)C>CN(C)C=O>[Cl:1][C:2]1[C:10]([C:11]2[CH:16]=[CH:15][C:14]([Cl:17])=[CH:13][CH:12]=2)=[CH:9][C:5]([C:6]([NH:19][C@@H:20]2[CH2:25][CH2:24][CH2:23][CH2:22][C@H:21]2[OH:26])=[O:8])=[CH:4][N:3]=1

参加物

6

反応物 4

HCID 81531DiisopropylethylamineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 12228412Cyclohexanol, 2-amino-, hydrochloride (1:1), (1R,2R)-HCID 866191836-Chloro-5-(4-chlorophenyl)-3-pyridinecarboxylic acid

生成物 1

HCID 866191846-chloro-5-(4-chloro-phenyl)-N-((1R,2R)-2-hydroxy-cyclohexyl)-nicotinamide収率 73%

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

実験手順

6-Chloro-5-(4-chloro-phenyl)-nicotinic acid (1.4 g, 5 mmol) was dissolved in N,N-dimethylformamide (30 mL). To this solution was added sequentially (1R,2R)-2-amino-cyclohexanol hydrochloride (0.87 g, 6 mmol), TBTU (1.84 g, 6 mmol), and N-ethyldiisopropylamine (4.47 mL, 26 mmol). The reaction mixture was stirred at room temperature for 72 hours then concentrated in vacuo. The residue was then dissolved in ethyl acetate (100 mL) and washed with 0.5 N HCl (100 mL), saturated sodium bicarbonate (100 mL) and water (100 mL). The aqueous phases were extracted with ethyl acetate (2×100 mL), the organics were combined and the whole was dried over MgSO4 and concentrated in vacuo. The solid residue was purified by stirring with (ethylacetate/heptane 1:2, 50 mL) to give 6-chloro-5-(4-chloro-phenyl)-N-((1R,2R)-2-hydroxy-cyclohexyl)-nicotinamide as a colorless solid, 1.4 g (73% yield). m/z (ISP+): 364.9, 366.9 (M+H).

後処理

  1. concentrationthen concentrated in vacuo
  2. dissolutionThe residue was then dissolved in ethyl acetate (100 mL)
  3. washwashed with 0.5 N HCl (100 mL), saturated sodium bicarbonate (100 mL) and water (100 mL)
  4. extractionThe aqueous phases were extracted with ethyl acetate (2×100 mL)
  5. dry with materialthe whole was dried over MgSO4
  6. concentrationconcentrated in vacuo
  7. customThe solid residue was purified
  8. stirringby stirring with (ethylacetate/heptane 1:2, 50 mL)

出典と根拠

ORDレコード
ord-257f3894c5a64ad1a8c9787558b1f0ef
出典データセット
uspto-grants-2010_08
特許番号
US07781593B2

反応ノート

読み込み中…