1-Hydroxybenzotriazole → HCID 68678614、化合物

HRID 1989069ノート

反応式

HRID 1989069 の反応式
C(OC(=O)[NH:7][C:8]1[CH:13]=[CH:12][CH:11]=[C:10]([CH:14]2[CH2:19][CH2:18][NH:17][CH2:16][CH2:15]2)[CH:9]=1)(C)(C)C.[CH3:21][N:22]1[CH2:27][CH2:26][N:25]([CH2:28][C:29](O)=[O:30])[CH2:24][CH2:23]1.C1C=CC2N(O)N=NC=2C=1.CCN(C(C)C)C(C)C>CN(C=O)C.C(Cl)Cl.O>[NH2:7][C:8]1[CH:9]=[C:10]([CH:14]2[CH2:15][CH2:16][N:17]([C:29](=[O:30])[CH2:28][N:25]3[CH2:26][CH2:27][N:22]([CH3:21])[CH2:23][CH2:24]3)[CH2:18][CH2:19]2)[CH:11]=[CH:12][CH:13]=1

参加物

8

反応物 4

HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 2762732(4-Methylpiperazin-1-yl)acetic acidHCID 29948324tert-Butyl [3-(piperidin-4-yl)phenyl]carbamate

生成物 1

HCID 68678614HCID 68678614、化合物収率 96.6%

試薬・触媒・溶媒 3

HCID 962Water溶媒HCID 6228Dimethylformamide溶媒HCID 6344Dichloromethane溶媒

実験手順

(3-Piperidin-4-yl-phenyl)-carbamic acid tert-butyl ester (0.20 g, 0.72 mmol), (4-methyl-piperazin-1-yl)-acetic acid (0.11 g, 0.72 mmol), HOBt (0.10 g, 0.72 mmol), DCI (0.14 g, 0.72 mmol), and DIEA (0.10 g, 0.72 mmol) were all combined in DMF (5 mL). After 16 h, water (10 mL) and CH2Cl2 (10 mL) were added. The organic layer was washed with water (3×10 mL), dried (MgSO4) and concentrated. Chromatography (0-15% EtOAc/hexanes gradient) provided 0.22 g (73%) of 1-[4-(3-Amino-phenyl)-piperidin-1-yl]-2-(4-methyl-piperazin-1-yl)-ethanone. (3-(1-[2-(4-Methyl-piperazin-1-yl)-acetyl]-piperidin-4-yl-1-phenyl)-carbamic acid tert-butyl ester (0.72 mmol) was diluted in CH2Cl2 (3 mL) and TFA (3 mL) was added. After 1 h, the reaction mixture was concentrated. Water (2 mL) was added and the solution was frozen and lyophilized overnight to provide (0.18 g) (81%) of 1-[4-(3-Amino-phenyl)-piperidin-1-yl]-2-(4-methyl-piperazin-1-yl)-ethanone. 8-indan-5-yl-2-methanesulfonyl-5-oxo-5,8-dihydro-pyrido[2,3-d]pyrimidine-6-carboxylic acid ethyl ester (32.5 mg, 0.079 mmol) and 1-[3-(4-amino-phenyl)-piperidin-1-yl]-2-dimethylamino-ethanone di-TFA salt (38.5 mg g, 0.079 mmol) were combined in i-PrOH (1 mL) and TEA (17 mg, 0.16 mmol) was added and the mixture was heated to 90° C. After 3 h, the reaction mixture was concentrated and purified by preparative HPLC (30 mL/min 5-100% MeCN/H2O gradient over 10 min) and lyophilized to provide 16.5 mg of 2-{3-[1-(2-Dimethylamino-acetyl)-piperidin-4-yl]-phenylamino}-8-indan-5-yl-5-oxo-5,8-dihydro-pyrido[2,3-d]pyrimidine-6-carboxylic acid ethyl ester. 1H NMR (400 MHz, CDCl3) δ (ppm): 9.23 (s, 1H), 9.08 (br s, 1H), 8.40 (s, 1H), 7.44 (s, 1H), 7.17-7.29 (m, 4H), 7.08 (dd, 1H, J=1.9 Hz, J=7.9 Hz), 6.85 (d, 1H, J=7.6 Hz), 4.29 (q, 2H, J=7.1 Hz), 3.02 (br s, 2H), 2.88-2.93 (m, 5H), 2.66-2.73 (m, 2H), 2.32 (s, 6H), 2.05-2.12 (m, 2H), 1.75-1.84 (m, 2H), 1.55 (br s, 2H), 1.31 (t, 3H, J=7.1 Hz).

後処理

  1. washThe organic layer was washed with water (3×10 mL)
  2. dry with materialdried (MgSO4)
  3. concentrationconcentrated

出典と根拠

ORDレコード
ord-d0d6ed87bbea4526a3ec591d0971c494
出典データセット
uspto-grants-2010_01
特許番号
US07642270B2

反応ノート

読み込み中…