Pyridine → N-(4-(7-azabicyclo[2.2.1]heptan-7-yl)-2-cyanophenyl)-5-methyl-4-oxo-1,4-dihydroquinoline-3-carboxamide

HRID 1908226ノート

反応式

HRID 1908226 の反応式
[CH3:1][C:2]1[CH:11]=[CH:10][CH:9]=[C:8]2[C:3]=1[C:4](=[O:15])[C:5]([C:12]([OH:14])=O)=[CH:6][NH:7]2.[NH2:16][C:17]1[CH:24]=[CH:23][C:22]([N:25]2[CH:29]3[CH2:30][CH2:31][CH:26]2[CH2:27][CH2:28]3)=[CH:21][C:18]=1[C:19]#[N:20].C(P1(=O)OP(CCC)(=O)OP(CCC)(=O)O1)CC.N1C=CC=CC=1>CC1CCCO1.C(OCC)(=O)C>[CH:29]12[N:25]([C:22]3[CH:23]=[CH:24][C:17]([NH:16][C:12]([C:5]4[C:4](=[O:15])[C:3]5[C:8](=[CH:9][CH:10]=[CH:11][C:2]=5[CH3:1])[NH:7][CH:6]=4)=[O:14])=[C:18]([C:19]#[N:20])[CH:21]=3)[CH:26]([CH2:31][CH2:30]1)[CH2:27][CH2:28]2

参加物

7

反応物 4

HCID 1049PyridineHCID 111923Propylphosphonic anhydrideHCID 156185565-Methyl-4-oxo-1,4-dihydroquinoline-3-carboxylic acidHCID 575168442-Amino-5-(7-azabicyclo[2.2.1]heptan-7-yl)benzonitrile

生成物 1

HCID 46194420N-(4-(7-azabicyclo[2.2.1]heptan-7-yl)-2-cyanophenyl)-5-methyl-4-oxo-1,4-dihydroquinoline-3-carboxamide収率 49.3%

試薬・触媒・溶媒 2

HCID 73012-Methyltetrahydrofuran溶媒HCID 8857Ethyl Acetate溶媒

反応条件

温度
100 °C

実験手順

To a solution of 5-methyl-4-oxo-1,4-dihydroquinoline-3-carboxylic acid 35 (162 mg, 0.80 mmol) and 2-amino-5-(7-azabicyclo[2.2.1]heptan-7-yl)benzonitrile 23 (170 mg, 0.80 mmol) in 2-methyltetrahydrofuran (1.5 mL) was added propyl phosphonic acid cyclic anhydride (50% solution in ethyl acetate, 949.5 μL, 1.605 mmol) and pyridine (126 mg, 129 μL, 1.60 mmol). The reaction was capped and heated at 100° C. for 65 min with microwave irradiation. The reaction was cooled to room temperature, diluted with ethyl acetate (10 mL), and quenched with saturated Na2CO3 solution (6 mL). The organic layer was dried over Na2SO4, filtered and concentrated. Purification by silica gel chromatography (0-35% ethyl acetate in dichloromethane) provided N-(4-(7-azabicyclo[2.2.1]heptan-7-yl)-2-cyanophenyl)-5-methyl-4-oxo-1,4-dihydroquinoline-3-carboxamide (157 mg, 49% yield). LC/MS m/z 399.3 [M+H]+, retention time 1.47 min (RP-C18, 10-99% CH3CN/0.05% TFA over 3 min). 1H NMR (400.0 MHz, DMSO-d6) δ 12.77 (s, 1H), 12.75 (s, 1H), 8.77 (s, 1H), 8.11 (d, J=9.1 Hz, 1H), 7.64-7.60 (m, 1H), 7.55 (d, J=8.0 Hz, 1H), 7.34 (d, J=2.8 Hz, 1H), 7.27 (dd, J=2.8, 9.1 Hz, 1H), 7.23 (d, J=7.2 Hz, 1H), 4.32 (s, 2H), 2.91 (s, 3H), 1.65 (d, J=7.2 Hz, 4H), 1.42 (d, J=6.8 Hz, 4H).

後処理

  1. customThe reaction was capped
  2. temperatureThe reaction was cooled to room temperature
  3. customquenched with saturated Na2CO3 solution (6 mL)
  4. dry with materialThe organic layer was dried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customPurification by silica gel chromatography (0-35% ethyl acetate in dichloromethane)

出典と根拠

ORDレコード
ord-2cb2af87a8e14e03a305e9c02398c1ca
出典データセット
uspto-grants-2013_12
特許番号
US08598205B2

反応ノート

読み込み中…