Diisopropylethylamine → N2-(5-Cyclopropyl-1H-pyrazol-3-yl)-N6-[(1S)-1-(5-fluoropyridin-2-yl)ethyl]-3-nitropyridine-2,6-diamine

HRID 450361ノート

反応式

HRID 450361 の反応式
Cl[C:2]1[N:7]=[C:6]([NH:8][C:9]2[CH:13]=[C:12]([CH:14]3[CH2:16][CH2:15]3)[NH:11][N:10]=2)[C:5]([N+:17]([O-:19])=[O:18])=[CH:4][CH:3]=1.Cl.[F:21][C:22]1[CH:23]=[CH:24][C:25]([C@@H:28]([NH2:30])[CH3:29])=[N:26][CH:27]=1.C(N(C(C)C)CC)(C)C>CCCCO.C(OCC)(=O)C>[CH:14]1([C:12]2[NH:11][N:10]=[C:9]([NH:8][C:6]3[C:5]([N+:17]([O-:19])=[O:18])=[CH:4][CH:3]=[C:2]([NH:30][C@H:28]([C:25]4[CH:24]=[CH:23][C:22]([F:21])=[CH:27][N:26]=4)[CH3:29])[N:7]=3)[CH:13]=2)[CH2:16][CH2:15]1

参加物

6

反応物 3

HCID 81531DiisopropylethylamineHCID 589359036-Chloro-N-(5-cyclopropyl-1H-pyrazol-3-yl)-3-nitropyridin-2-amine2 回HCID 67123789(S)-1-(5-fluoropyridin-2-yl)ethanamine hydrochloride2 回

生成物 1

HCID 86649276N2-(5-Cyclopropyl-1H-pyrazol-3-yl)-N6-[(1S)-1-(5-fluoropyridin-2-yl)ethyl]-3-nitropyridine-2,6-diamine収率 65.7%

試薬・触媒・溶媒 2

HCID 2631-Butanol溶媒HCID 8857Ethyl Acetate溶媒

反応条件

温度
70 °C

実験手順

A mixture of 6-chloro-N-(5-cyclopropyl-1H-pyrazol-3-yl)-3-nitropyridin-2-amine (Intermediate 9, 0.5 g) and [(1S)-1-(5-fluoropyridin-2-yl)ethyl]amine hydrochloride (Intermediate 5, 0.35 g) in n-BuOH (10 mL) with diisopropylethylamine (1 mL) was stirred at 70° C. for 4 hours. The resulting mixture was diluted with ethyl acetate (20 mL), and washed with brine (10 mL×3). The organic layer was dried and concentrated. The resulting residue was separated by silica gel column (Hexane/Ethyl acetate) to yield 0.45 g of desired product. MS (electrospray): 384 (M+1) for C18H18FN7O2. 1H NMR (300 MHz, CD3OD) δ ppm 8.60 (s, 1H) 8.20 (m, 1H) 8.15 (m, 1H) 7.60 (m, 1H) 7.40 (s, 1H) 6.30 (d, 1H) 6.20 (s, 1H) 5.35 (m, 1H), 1.90 (m, 1H) 1.60 (d, 3H) 1.00 (m, 2H) 0.80 (m, 2H).

後処理

  1. washwashed with brine (10 mL×3)
  2. customThe organic layer was dried
  3. concentrationconcentrated
  4. customThe resulting residue was separated by silica gel column (Hexane/Ethyl acetate)

出典と根拠

ORDレコード
ord-f021bfc774554b07ac4ccd07c80f66f6
出典データセット
uspto-grants-2013_07
特許番号
US08486966B2

反応ノート

読み込み中…