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

HRID 1522358Notes

Reaction equation

HRID 1522358 reaction equation
[CH:1]1([C:4]2[CH:5]=[C:6]([C:16]([OH:18])=O)[C:7]3[CH:12]=[N:11][N:10]([CH:13]([CH3:15])[CH3:14])[C:8]=3[N:9]=2)[CH2:3][CH2:2]1.Cl.[NH2:20][CH2:21][C:22]1[C:23](=[O:32])[NH:24][C:25]([CH:29]2[CH2:31][CH2:30]2)=[CH:26][C:27]=1[CH3:28].ON1C2N=CC=CC=2N=N1.C(Cl)CCl.CN1CCOCC1>O.CS(C)=O>[CH:1]1([C:4]2[CH:5]=[C:6]([C:16]([NH:20][CH2:21][C:22]3[C:23](=[O:32])[NH:24][C:25]([CH:29]4[CH2:30][CH2:31]4)=[CH:26][C:27]=3[CH3:28])=[O:18])[C:7]3[CH:12]=[N:11][N:10]([CH:13]([CH3:14])[CH3:15])[C:8]=3[N:9]=2)[CH2:2][CH2:3]1

Participants

8

Reactant 5

HCID 111,2-DichloroethaneHCID 79724-MethylmorpholineHCID 181649HOAtHCID 25259926-cyclopropyl-1-(propan-2-yl)-1H-pyrazolo[3,4-b]pyridine-4-carboxylic acidHCID 671241643-(Aminomethyl)-6-cyclopropyl-4-methyl-2(1H)-pyridinone hydrochloride

Product 1

HCID 680787866-Cyclopropyl-N-[(6-cyclopropyl-4-methyl-2-oxo-1,2-dihydro-3-pyridinyl)methyl]-1-(1-methylethyl)-1H-pyrazolo[3,4-b]pyridine-4-carboxamide

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 962WaterSolvent

Procedure

To a 4 mL solution of DMSO were sequentially added 6-cyclopropyl-1-(1-methylethyl)-1H-pyrazolo[3,4-b]pyridine-4-carboxylic acid (0.11 g, 0.448 mmol), 3-(aminomethyl)-6-cyclopropyl-4-methyl-2(1H)-pyridinone hydrochloride (0.106 g, 0.493 mmol), 1-hydroxy-7-azabenzotriazole (0.073 g, 0.538 mmol), EDC (0.103 g, 0.538 mmol), and then N-methylmorpholine (0.197 mL, 1.79 mmol) via syringe. After stirring overnight at room temperature, the suspension was diluted with 50 mL of water and stirred for 15 min. After standing at room temperature for 15 min., the reaction mixture was filtered and the collected solid washed with additional water. The solid was then dried in a vacuum oven at 45° C. for 4 h. The product was obtained as 0.165 g (89%). LCMS E-S (M+H)=406.5. 1H NMR (400 MHz, DMSO-d6) δ ppm 0.76-0.82 (m, 2 H), 0.91-0.98 (m, 2 H), 1.03-1.12 (m, 4 H), 1.46 (d, J=6.82 Hz, 6 H), 1.74-1.84 (m, 1 H), 2.19 (s, 3 H), 2.21-2.31 (m, 1 H), 4.34 (d, J=5.05 Hz, 2 H), 5.05-5.18 (m, 1 H), 5.73 (s, 1 H), 7.42 (s, 1 H), 8.21 (s, 1 H), 8.72 (t, J=4.93 Hz, 1 H), 11.61 (br. s., 1 H).

Workup

  1. stirringstirred for 15 min
  2. waitAfter standing at room temperature for 15 min.
  3. filtrationthe reaction mixture was filtered
  4. washthe collected solid washed with additional water
  5. customThe solid was then dried in a vacuum oven at 45° C. for 4 h
  6. customThe product was obtained as 0.165 g (89%)

Sources & evidence

ORD record
ord-da5695d315cd4c7791c65a25f7ab8428
Source dataset
uspto-grants-2015_07
Patent number
US09073924B2

Reaction notes

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