1,2-Dichloroethane → (4,6-dimethyl-2-oxo-1,2-dihydro-3-pyridinyl)methyl 6-cyclopropyl-1-[2-({[(1,1-dimethylethyl)oxy]carbonyl}amino)ethyl]-1H-pyrazolo[3,4-b]pyridine-4-carboxylate

HRID 1522455Notes

Reaction equation

HRID 1522455 reaction equation
[CH:1]1([C:4]2[CH:5]=[C:6]([C:23]([OH:25])=[O:24])[C:7]3[CH:12]=[N:11][N:10]([CH2:13][CH2:14][NH:15][C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[C:8]=3[N:9]=2)[CH2:3][CH2:2]1.N[CH2:27][C:28]1[C:29](=[O:36])[NH:30][C:31]([CH3:35])=[CH:32][C:33]=1[CH3:34].ON1C2N=CC=CC=2N=N1.C(Cl)CCl.CN1CCOCC1>O.CS(C)=O>[CH:1]1([C:4]2[CH:5]=[C:6]([C:23]([O:25][CH2:27][C:28]3[C:29](=[O:36])[NH:30][C:31]([CH3:35])=[CH:32][C:33]=3[CH3:34])=[O:24])[C:7]3[CH:12]=[N:11][N:10]([CH2:13][CH2:14][NH:15][C:16]([O:18][C:19]([CH3:22])([CH3:20])[CH3:21])=[O:17])[C:8]=3[N:9]=2)[CH2:3][CH2:2]1

Participants

8

Reactant 5

HCID 111,2-DichloroethaneHCID 79724-MethylmorpholineHCID 181649HOAtHCID 70638443-(Aminomethyl)-4,6-dimethyl-1,2-dihydropyridin-2-oneHCID 680785376-Cyclopropyl-1-[2-({[(1,1-dimethylethyl)oxy]carbonyl}amino)ethyl]-1H-pyrazolo[3,4-b]pyridine-4-carboxylic acid

Product 1

HCID 71281275(4,6-dimethyl-2-oxo-1,2-dihydro-3-pyridinyl)methyl 6-cyclopropyl-1-[2-({[(1,1-dimethylethyl)oxy]carbonyl}amino)ethyl]-1H-pyrazolo[3,4-b]pyridine-4-carboxylate

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 962WaterSolvent

Procedure

To a solution of DMSO (10 mL) were sequentially added 6-cyclopropyl-1-[2-({[(1,1-dimethylethyl)oxy]carbonyl}amino)ethyl]-1H-pyrazolo[3,4-b]pyridine-4-carboxylic acid (270 mg, 0.779 mmol), 3-(aminomethyl)-4,6-dimethyl-2(1H)-pyridinone (178 mg, 1.169 mmol), and 1-hydroxy-7-azabenzotriazole (212 mg, 1.559 mmol), and the mixture stirred at room temperature for 10 min. Next was added EDC (299 mg, 1.559 mmol) and N-methylmorpholine (0.343 mL, 3.12 mmol), and reaction mixture was stirred at room temperature for 16 h. The contents were diluted with water (25 mL) and stirred for 10 min. The solid product was filtered off, dried, and collected as 0.290 g (98%). LCMS E-S (M+H)=381.2. 1H NMR (400 MHz, DMSO-d6) δ ppm 1.00-1.15 (m, 4 H), 1.30 (s, 9H), 2.13 (s, 3 H), 2.18-2.32 (m, 4 H), 4.36 (d, J=4.80 Hz, 2 H), 4.42 (t, J=5.81 Hz, 2 H), 5.90 (s, 1 H), 6.85 (t, J=5.56 Hz, 1 H), 7.44 (s, 1 H), 8.22 (s, 2 H), 8.73 (t, J=4.67 Hz, 1 H), 11.57 (br. s., 1 H).

Workup

  1. additionNext was added
  2. stirringwas stirred at room temperature for 16 h
  3. stirringstirred for 10 min
  4. filtrationThe solid product was filtered off
  5. customdried
  6. customcollected as 0.290 g (98%)

Sources & evidence

ORD record
ord-69692a8b9ae646e68192110fc2e1965a
Source dataset
uspto-grants-2015_07
Patent number
US09073924B2

Reaction notes

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