Sodium Chloride → N-((6-amino-2-methylpyridin-3-yl)methyl)-1-((2-methylquinolin-6-yl)methyl)-1H-pyrazole-4-carboxamide

HRID 928442Notes

Reaction equation

HRID 928442 reaction equation
[CH3:1][C:2]1[CH:11]=[CH:10][C:9]2[C:4](=[CH:5][CH:6]=[C:7]([CH2:12][N:13]3[CH:17]=[C:16]([C:18]([OH:20])=O)[CH:15]=[N:14]3)[CH:8]=2)[N:3]=1.[Na+].[Cl-].CCN=C=NCCCN(C)C.Cl.C1C=NC2N(O)N=NC=2C=1.CN1CCOCC1.[NH2:52][CH2:53][C:54]1[CH:55]=[CH:56][C:57]([NH2:61])=[N:58][C:59]=1[CH3:60]>CN(C=O)C.CO.C(#N)C>[NH2:61][C:57]1[N:58]=[C:59]([CH3:60])[C:54]([CH2:53][NH:52][C:18]([C:16]2[CH:15]=[N:14][N:13]([CH2:12][C:7]3[CH:8]=[C:9]4[C:4](=[CH:5][CH:6]=3)[N:3]=[C:2]([CH3:1])[CH:11]=[CH:10]4)[CH:17]=2)=[O:20])=[CH:55][CH:56]=1

Participants

10

Reactant 6

HCID 5234Sodium ChlorideHCID 79724-MethylmorpholineHCID 181649HOAtHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 101977255-(Aminomethyl)-6-methylpyridin-2-amineHCID 580812841-((2-methylquinolin-6-yl)methyl)-1H-pyrazole-4-carboxylic acid

Product 1

HCID 66723582N-((6-amino-2-methylpyridin-3-yl)methyl)-1-((2-methylquinolin-6-yl)methyl)-1H-pyrazole-4-carboxamide

Reagents, catalysts & solvents 3

HCID 887MethanolSolvent2×HCID 6228DimethylformamideSolventHCID 6342AcetonitrileSolvent

Conditions

Temperature
50 °C

Procedure

To a suspension of 1-((2-methylquinolin-6-yl)methyl)-1H-pyrazole-4-carboxylic acid (incl. NaCl) (100 mg, 0.337 mmol), EDC.HCl (84 mg, 0.438 mmol) and HOAt (59.6 mg, 0.438 mmol) in DMF (1 ml) was added N-methylmorpholine (0.185 ml, 1.684 mmol). The reaction mixture was stirred for 1 h at 50° C., then 5-(aminomethyl)-6-methylpyridin-2-amine (70.7 mg, 0.337 mmol) was added. Stirring continued at 50° C. for 18 h. Reaction mixture was diluted with methanol, then applied onto a PL-SO3H cartridge (500 mg/6 ml by VARIAN) to catch the desired amine product, washed the cartridge with DMF, DCM and MeOH to remove all impurities, then the product was released from the cartridge by washing with 2M NH3 in MeOH. The basic filtrate was evaporated to give the crude material, which was treated with 0.2 ml of MeOH and 1 ml of ACN in ultrasonic bath. The precipitate formed was filtered, washed with 1 ml of ACN and dried under high vacuum for 4 days to yield the title compound. HPLC (Method J) Rt=2.373 min, MS (Method V) [M+H]+=387.1.

Workup

  1. stirringStirring
  2. waitcontinued at 50° C. for 18 h
  3. customReaction mixture
  4. washwashed the cartridge with DMF, DCM and MeOH
  5. customto remove all impurities
  6. washby washing with 2M NH3 in MeOH
  7. customThe basic filtrate was evaporated
  8. customto give the crude material, which
  9. customThe precipitate formed
  10. filtrationwas filtered
  11. washwashed with 1 ml of ACN
  12. customdried under high vacuum for 4 days

Sources & evidence

ORD record
ord-1eee77baa79a4995a82d67ed559d2e14
Source dataset
uspto-grants-2016_03
Patent number
US09290485B2

Reaction notes

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