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 476063Notes

Reaction equation

HRID 476063 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, 4H), 1.30 (s, 9H), 2.13 (s, 3H), 2.18-2.32 (m, 4H), 4.36 (d, J=4.80 Hz, 2H), 4.42 (t, J=5.81 Hz, 2H), 5.90 (s, 1H), 6.85 (t, J=5.56 Hz, 1H), 7.44 (s, 1H), 8.22 (s, 2H), 8.73 (t, J=4.67 Hz, 1H), 11.57 (br. s., 1H).

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-e8a410779f6e46159d23f6ffd0cd95af
Source dataset
uspto-grants-2014_01
Patent number
US08637509B2

Reaction notes

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