2-Pyridinecarboxamide → N-[2-(1,1-Dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-6-methylquinolin-4-yl]pyridine-2-carboxamide

HRID 540184

反応式

HRID 540184 の反応式
[N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[C:7]([NH2:9])=[O:8].Cl[C:11]1[C:20]2[C:15](=[CH:16][CH:17]=[C:18](OC(F)(F)F)[CH:19]=2)[N:14]=[C:13]([N:26]2[CH2:32][C:31]3[CH:33]=[CH:34][CH:35]=[CH:36][C:30]=3[S:29](=[O:38])(=[O:37])[CH2:28][CH2:27]2)[CH:12]=1.[CH:39]1(N)CCCC(N)C1.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>O1CCOCC1.[Cu]I>[O:37]=[S:29]1(=[O:38])[C:30]2[CH:36]=[CH:35][CH:34]=[CH:33][C:31]=2[CH2:32][N:26]([C:13]2[CH:12]=[C:11]([NH:9][C:7]([C:2]3[CH:3]=[CH:4][CH:5]=[CH:6][N:1]=3)=[O:8])[C:20]3[C:15](=[CH:16][CH:17]=[C:18]([CH3:39])[CH:19]=3)[N:14]=2)[CH2:27][CH2:28]1

参加物

7

反応物 4

HCID 150702-PyridinecarboxamideHCID 188141,3-CyclohexanediamineHCID 62657Potassium Phosphate, TribasicHCID 712545694-(4-Chloro-6-(trifluoromethoxy)quinolin-2-yl)-2,3,4,5-tetrahydro-1,4-benzothiazepine 1,1-dioxide

生成物 1

HCID 71262128N-[2-(1,1-Dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-6-methylquinolin-4-yl]pyridine-2-carboxamide収率 70.9%

試薬・触媒・溶媒 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)触媒HCID 312751,4-Dioxane溶媒

反応条件

温度
150 °C

実験手順

A mixture of pyridine-2-carboxylic acid amide (99 mg, 0.8 mmol), 4-(4-chloro-6-methylquinolin-2-yl)-2,3,4,5-tetrahydro-1,4-benzothiazepine 1,1-dioxide (300 mg, 0.8 mmol, prepared in analogy to 4-(4-chloro-6-(trifluoromethoxy)quinolin-2-yl)-2,3,4,5-tetrahydro-1,4-benzothiazepine 1,1-dioxide in Example 17-1), cyclohexane-1,3-diamine (90 mg, 0.08 mmol), copper(I) iodide (1.5 mg, 0.008 mmol) and potassium phosphate (340 mg, 1.6 mmol) in 1,4-dioxane (3 mL) was heated in a 5 mL of microwave process vial for 3 hours at 150° C. The reaction mixture was concentrated in vacuo. The residue was purified by preparative HPLC and SPE to give 26 mg of the desired product (yield was 7.1%). MS obsd. (ESI+) [(M+H)+] 451, 1H NMR (400 MHz, CD3OD) δ ppm 8.90-8.82 (d, J=8 Hz, 1 H), 8.77 (s, 1 H), 8.47-8.40 (d, J=7.6 Hz, 1 H), 8.20-8.13 (t, J=6.4 Hz, 1 H), 8.13-8.08 (d, J=7.6 Hz, 2 H), 7.92-7.85 (m, 2 H), 7.80-7.70 (q, J=8.4 Hz, 3 H), 7.62-7.56 (t, J=7.2 Hz, 1 H), 5.37 (s, 2 H), 4.80-4.50 (m, 2 H), 3.82-3.78 (t, J=2.8 Hz, 2 H), 2.60 (s, 3 H).

後処理

  1. concentrationThe reaction mixture was concentrated in vacuo
  2. customThe residue was purified by preparative HPLC and SPE

出典と根拠

ORDレコード
ord-deee6e5075f240819eb98a24bf677660
出典データセット
uspto-grants-2014_10
特許番号
US08871756B2

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