Hydrazine → 3-Amino-N-[4-(3-aminocyclohexyl)pyridin-3-yl]-7-ethylquinoline-2-carboxamide

HRID 924412Notes

Reaction equation

HRID 924412 reaction equation
[NH2:1][C:2]1[C:3]([C:14]([OH:16])=O)=[N:4][C:5]2[C:10]([CH:11]=1)=[CH:9][CH:8]=[C:7]([CH2:12][CH3:13])[CH:6]=2.[NH2:17][C:18]1[CH:19]=[N:20][CH:21]=[CH:22][C:23]=1[CH:24]1[CH2:29][CH2:28][CH2:27][CH:26]([N:30]2C(=O)C3C(=CC=CC=3)C2=O)[CH2:25]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.[OH-].[Na+].NN>CN(C=O)C.CO>[NH2:1][C:2]1[C:3]([C:14]([NH:17][C:18]2[CH:19]=[N:20][CH:21]=[CH:22][C:23]=2[CH:24]2[CH2:29][CH2:28][CH2:27][CH:26]([NH2:30])[CH2:25]2)=[O:16])=[N:4][C:5]2[C:10]([CH:11]=1)=[CH:9][CH:8]=[C:7]([CH2:12][CH3:13])[CH:6]=2

Participants

9

Reactant 6

HCID 9321HydrazineHCID 14798Sodium HydroxideHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 59226443HCID 59226443, compoundHCID 867268773-Amino-7-ethylquinoline-2-carboxylic acid

Product 1

HCID 778440263-Amino-N-[4-(3-aminocyclohexyl)pyridin-3-yl]-7-ethylquinoline-2-carboxamide

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6228DimethylformamideSolvent2×

Procedure

A mixture of 3-amino-7-ethylquinoline-2-carboxylic acid (0.040 g, 0.18 mmol), 2-[3-(3-aminopyridin-4-yl)cyclohexyl]-1H-isoindole-1,3(2H)-dione (0.055 g, 0.17 mmol), HATU (0.22 g, 0.58 mmol), DMF (0.65 mL) and DIPEA (0.076 g, 0.59 mmol) was stirred at room temperature for 16 h. Aq. NaOH (1 M) was added to the reaction mixture, and a precipitate formed, which was collected by vacuum filtration. The collected solid was washed with 1 M NaOH, followed by water and dried under vacuum to afford an intermediate. The intermediate was dissolved in DMF (0.15 mL) and hydrazine (0.15 mL) was added. The resulting reaction mixture was stirred at room temperature for 16 h, diluted with MeOH, filtered and purified by preparative LC MS (XBridge™ preparative C18 5 μm 30×10 mm OBD™ column, flow rate 60 mL/min., eluting with a gradient of MeCN and water with 0.15% NH4OH) to give title compound. LCMS calc. for C23H28N5O (M+H)+: m/z=390.2. Found: 390.1.

Workup

  1. customa precipitate formed
  2. filtrationwhich was collected by vacuum filtration
  3. washThe collected solid was washed with 1 M NaOH
  4. customdried under vacuum
  5. customto afford an intermediate
  6. customThe resulting reaction mixture
  7. stirringwas stirred at room temperature for 16 h
  8. filtrationfiltered
  9. custompurified by preparative LC MS (XBridge™ preparative C18 5 μm 30×10 mm OBD™ column, flow rate 60 mL/min.
  10. washeluting with a gradient of MeCN and water with 0.15% NH4OH)

Sources & evidence

ORD record
ord-d6bef013f78a4cb2a31fb30abe8712eb
Source dataset
uspto-grants-2016_03
Patent number
US09278950B2

Reaction notes

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