Cyclohexylamine → (3S,6R)-1-[2-Amino-6-(1H-indazol-6-yl)-4-pyrimidinyl]-N-cyclohexyl-6-methyl-3-piperidinecarboxamide

HRID 2367482ノート

反応式

HRID 2367482 の反応式
[NH2:1][C:2]1[N:7]=[C:6]([N:8]2[C@H:13]([CH3:14])[CH2:12][CH2:11][C@H:10]([C:15]([OH:17])=O)[CH2:9]2)[CH:5]=[C:4]([C:18]2[CH:26]=[C:25]3[C:21]([CH:22]=[N:23][NH:24]3)=[CH:20][CH:19]=2)[N:3]=1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C.[CH:60]1([NH2:66])[CH2:65][CH2:64][CH2:63][CH2:62][CH2:61]1>CN(C=O)C.CCOC(C)=O.O>[NH2:1][C:2]1[N:7]=[C:6]([N:8]2[C@H:13]([CH3:14])[CH2:12][CH2:11][C@H:10]([C:15]([NH:66][CH:60]3[CH2:65][CH2:64][CH2:63][CH2:62][CH2:61]3)=[O:17])[CH2:9]2)[CH:5]=[C:4]([C:18]2[CH:26]=[C:25]3[C:21]([CH:22]=[N:23][NH:24]3)=[CH:20][CH:19]=2)[N:3]=1

参加物

8

反応物 4

HCID 7965CyclohexylamineHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 58504583(3S,6R)-1-[2-amino-6-(1H-indazol-6-yl)-4-pyrimidinyl]-6-methyl-3-piperidinecarboxylic acid

生成物 1

HCID 58504833(3S,6R)-1-[2-Amino-6-(1H-indazol-6-yl)-4-pyrimidinyl]-N-cyclohexyl-6-methyl-3-piperidinecarboxamide収率 85.4%

試薬・触媒・溶媒 3

HCID 962Water溶媒HCID 6228Dimethylformamide溶媒HCID 8857Ethyl Acetate溶媒

実験手順

To a solution of (3S,6R)-1-[2-amino-6-(1H-indazol-6-yl)-4-pyrimidinyl]-6-methyl-3-piperidinecarboxylic acid (95 mg, 0.270 mmol) and HATU (123 mg, 0.324 mmol) in DMF (3 mL) was added Hunig's base (0.094 mL, 0.54 mmol), and the mixture was stirred at room temperature for 15 minutes. Then cyclohexylamine (0.037 mL, 0.324 mmol) was added, and the reaction mixture was stirred at room temperature for 0.5 hours. LCMS showed reaction was completed. The reaction was poured into water, and EtOAc was added to extract the product. The product stayed in the EtOAc layer. The organic layer was concentrated to dryness, and the resulting glass like solid was dissolved in CH3OH. Water was poured into the solution, and a white solid was formed, which was filtered, washed by water, and dried under vacuum to give the title compound (100 mg) as a white solid. LC-MS (ES) m/z=434 [M+H]+. 1H NMR (400 MHz, CD3OD): δ 1.29 (m, 9H), 1.62-2.09 (m, 9H), 2.32-2.45 (m, 1H), 3.06-3.18 (m, 1H), 3.61-3.73 (m, 1H), 4.44-4.84 (m, 1H), 6.53 (s, 1H), 7.65 (dd, J=8.5, 1.4 Hz, 1H), 7.85 (dd, J=8.5, 1.4 Hz, 1H), 8.06 (s, 1H), 8.09 (s, 1H).

後処理

  1. stirringthe reaction mixture was stirred at room temperature for 0.5 hours
  2. customreaction
  3. additionwas added
  4. extractionto extract the product
  5. concentrationThe organic layer was concentrated to dryness
  6. dissolutionthe resulting glass like solid was dissolved in CH3OH
  7. additionWater was poured into the solution
  8. customa white solid was formed
  9. filtrationwhich was filtered
  10. washwashed by water
  11. customdried under vacuum

出典と根拠

ORDレコード
ord-6c76958519e9486787547ee9467e0e6c
出典データセット
uspto-grants-2014_04
特許番号
US08697685B2

反応ノート

読み込み中…