1-Hydroxybenzotriazole → HCID 68678614, 화합물

HRID 1989069노트

반응식

HRID 1989069 반응식
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

참가 물질

8

반응물 4

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

생성물 1

HCID 68678614HCID 68678614, 화합물수율 96.6%

시약·촉매·용매 3

HCID 962Water용매HCID 6228Dimethylformamide용매HCID 6344Dichloromethane용매

실험 절차

(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).

후처리

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

출처 및 근거

ORD 기록
ord-d0d6ed87bbea4526a3ec591d0971c494
출처 데이터셋
uspto-grants-2010_01
특허 번호
US07642270B2

반응 노트

불러오는 중…