Water → HCID 46199030、化合物

HRID 1514314ノート

反応式

HRID 1514314 の反応式
CS(O)(=O)=O.[NH2:6][CH2:7][C:8]1[CH:9]=[C:10]2[C:14](=[CH:15][CH:16]=1)[C:13](=[O:17])[N:12]([CH:18]1[CH2:23][CH2:22][C:21](=[O:24])[NH:20][C:19]1=[O:25])[CH2:11]2.C1N=CN([C:31](N2C=NC=C2)=[O:32])C=1.[F:38][C:39]1[CH:44]=[C:43]([F:45])[CH:42]=[CH:41][C:40]=1[C:46]1[N:47]=[C:48]([NH2:51])[S:49][CH:50]=1.O>CN(C=O)C.C(OCC)(=O)C>[F:38][C:39]1[CH:44]=[C:43]([F:45])[CH:42]=[CH:41][C:40]=1[C:46]1[N:47]=[C:48]([NH:51][C:31]([NH:6][CH2:7][C:8]2[CH:9]=[C:10]3[C:14](=[CH:15][CH:16]=2)[C:13](=[O:17])[N:12]([CH:18]2[CH2:23][CH2:22][C:21](=[O:24])[NH:20][C:19]2=[O:25])[CH2:11]3)=[O:32])[S:49][CH:50]=1

参加物

7

反応物 4

HCID 962WaterHCID 682631,1'-CarbonyldiimidazoleHCID 6113704-(2,4-Difluorophenyl)-1,3-thiazol-2-amineHCID 866307653-(5-(Aminomethyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione methanesulfonate

生成物 1

HCID 46199030HCID 46199030、化合物収率 13%

試薬・触媒・溶媒 2

HCID 6228Dimethylformamide溶媒HCID 8857Ethyl Acetate溶媒

実験手順

A mixture of 3-(5-aminomethyl-1-oxo-1,3-dihydro-isoindol-2-yl)-piperidine-2,6-dione methanesulfonic acid salt (0.40 g, 1.1 mmol) and CDI (0.18 g, 1.1 mmol) in DMF (5 mL) was stirred at room temperature for 18 h. To the mixture was added 4-(2,4-difluoro-phenyl)-thiazol-2-ylamine (0.23 g, 1.1 mmol) at room temperature, and the mixture was stirred at 100° C. for 2 days. To the mixture was added water (25 mL) and ethyl acetate (20 mL). The mixture was stirred at room temperature for 2 h. The suspension was filtered and the solid was washed with water (20 mL), ethyl acetate (20 mL) and water (20 mL) to give a solid. The solid was purified with Prep HPLC to give 1-[4-(2,4-difluoro-phenyl)-thiazol-2-yl]-3-[2-(2,6-dioxo-piperidin-3-yl)-1-oxo-2,3-dihydro-1H-isoindol-5-ylmethyl]-urea as a white solid (70 mg, 13% yield): HPLC: Waters Symmetry C18, 5 μm, 3.9×150 mm, 1 mL/min, 240 nm, 40/60 CH3CN/0.% H3PO4, 6.43 min (97.7%); mp: 264-266° C.; 1H NMR (DMSO-d6) 1.93-2.05 (m, 1H, CHH), 2.30-2.45 (m, 1H, CHH), 2.55-2.68 (m, 1H, CHH), 2.82-3.00 (m, 1H, CHH), 4.32 (d, J=17.4 Hz, 1H, CHH), 4.41-4.54 (m, 3H, CH2, CHH), 5.11 (dd, J=5.1, 13.2 Hz, 1H, NCH), 7.09-7.24 (m, 2H, Ar, NH), 7.28-7.41 (m, 2H, Ar), 7.46 (d, J=7.7 Hz, 1H, Ar), 7.53 (s, 1H, Ar), 7.71 (d, J=7.9 Hz, 1H, Ar), 7.93-8.10 (m, 1H, Ar), 10.85 (s, 1H, NH), 10.98 (s, 1H, NH); 13C NMR (DMSO-d6) 22.48, 31.18, 42.94, 47.12, 51.57, 104.54 (t, JC-F=26.4 Hz), 110.67 (d, JC-F=14.3 Hz), 111.81 (dd, JC-F=3.3, 20.9 Hz), 118.91 (dd, JC-F=2.8. 11.6 Hz), 121.95, 123.03, 126.95, 130.29 (dd, JC-F=4.4, 9.9 Hz), 130.49, 141.44, 142.45, 143.95, 154.02, 159.48 (dd, JC-F=252.2, 12.1 Hz), 159.36, 161.24 (dd, JC-F=246.9, 13.2 Hz), 167.88, 170.98, 172.85; LCMS MH=512; Anal. Calcd for C24H19N5O4F2S: C, 56.36; H, 3.74; N, 13.69; Found: C, 56.16; H, 3.80; N, 14.07.

後処理

  1. stirringthe mixture was stirred at 100° C. for 2 days
  2. stirringThe mixture was stirred at room temperature for 2 h
  3. filtrationThe suspension was filtered
  4. washthe solid was washed with water (20 mL), ethyl acetate (20 mL) and water (20 mL)
  5. customto give a solid
  6. customThe solid was purified with Prep HPLC

出典と根拠

ORDレコード
ord-99fa269d8e5c4da1b40ec04f898bb9ff
出典データセット
uspto-grants-2012_07
特許番号
US08222249B2

反応ノート

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