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

HRID 2367482Notes

Reaction equation

HRID 2367482 reaction equation
[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

Participants

8

Reactant 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

Product 1

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

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

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).

Workup

  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

Sources & evidence

ORD record
ord-6c76958519e9486787547ee9467e0e6c
Source dataset
uspto-grants-2014_04
Patent number
US08697685B2

Reaction notes

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