1,2-Dichloroethane → 1-(1-Methylethyl)-N-[(6-methyl-2-oxo-4-propyl-1,2-dihydro-3-pyridinyl)methyl]-6-(4-pyridinyl)-1H-pyrazolo[3,4-b]pyridine-4-carboxamide

HRID 475959Notes

Reaction equation

HRID 475959 reaction equation
[CH3:1][CH:2]([N:4]1[C:8]2[N:9]=[C:10]([C:16]3[CH:21]=[CH:20][N:19]=[CH:18][CH:17]=3)[CH:11]=[C:12]([C:13](O)=[O:14])[C:7]=2[CH:6]=[N:5]1)[CH3:3].[NH2:22][CH2:23][C:24]1[C:25](=[O:34])[NH:26][C:27]([CH3:33])=[CH:28][C:29]=1[CH2:30][CH2:31][CH3:32].C(Cl)CCl.C1C=NC2N(O)N=NC=2C=1.CN1CCOCC1>CN(C=O)C.O>[CH3:1][CH:2]([N:4]1[C:8]2[N:9]=[C:10]([C:16]3[CH:21]=[CH:20][N:19]=[CH:18][CH:17]=3)[CH:11]=[C:12]([C:13]([NH:22][CH2:23][C:24]3[C:25](=[O:34])[NH:26][C:27]([CH3:33])=[CH:28][C:29]=3[CH2:30][CH2:31][CH3:32])=[O:14])[C:7]=2[CH:6]=[N:5]1)[CH3:3]

Participants

8

Reactant 5

HCID 111,2-DichloroethaneHCID 79724-MethylmorpholineHCID 181649HOAtHCID 201146251-(1-Methylethyl)-6-(4-pyridinyl)-1H-pyrazolo[3,4-b]pyridine-4-carboxylic acidHCID 671241403-(Aminomethyl)-6-methyl-4-propylpyridin-2(1H)-oneacetate

Product 1

HCID 565975621-(1-Methylethyl)-N-[(6-methyl-2-oxo-4-propyl-1,2-dihydro-3-pyridinyl)methyl]-6-(4-pyridinyl)-1H-pyrazolo[3,4-b]pyridine-4-carboxamide

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

1-(1-Methylethyl)-6-(4-pyridinyl)-1H-pyrazolo[3,4-b]pyridine-4-carboxylic acid (150 mg, 0.531 mmol), 3-(aminomethyl)-6-methyl-4-propyl-2(1H)-pyridinone (115 mg, 0.531 mmol), EDC (122 mg, 0.638 mmol), HOAt (72.3 mg, 0.531 mmol), and N-methylmorpholine (0.233 mL, 2.12 mmol) were suspended in DMF (5 mL) and stirred at room temperature overnight. water was added to the reaction mixture, and the contents were filtered. The filter cake was washed with additional water (2×). The crude solid was purified by reverse phase HPLC (mobile phase: 10-30% ACN in H2O, 0.1% TFA). The isolated solid was then neutralized with saturated NaHCO3, and washed with EtOAc (5×15 mL). The combined organic layers were dried over Na2SO4, filtered, and concentrated in vacuo to afford the title compound as an off-white solid, 0.060 g (24%). LCMS E-S (M+H)=445.3. 1H NMR (400 MHz, DMSO-d6) δ ppm 0.84-0.92 (m, 3H), 1.47-1.54 (m, 2H), 1.57 (d, J=6.82 Hz, 6H), 2.14 (s, 3H), 2.48-2.52 (m, 2H), 4.42-4.49 (m, 2H), 5.33-5.43 (m, 1H), 5.90-5.96 (m, 1H), 8.28-8.37 (m, 3H), 8.44-8.48 (m, 1H), 8.82-8.87 (m, 2H), 8.99-9.04 (m, 1H), 11.58 (s, 1H).

Workup

  1. filtrationthe contents were filtered
  2. washThe filter cake was washed with additional water (2×)
  3. customThe crude solid was purified by reverse phase HPLC (mobile phase: 10-30% ACN in H2O, 0.1% TFA)
  4. washwashed with EtOAc (5×15 mL)
  5. dry with materialThe combined organic layers were dried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-f86b97b0a33c465ba8f79344be909753
Source dataset
uspto-grants-2014_01
Patent number
US08637509B2

Reaction notes

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