Sodium Carbonate → HCID 68294930, compound

HRID 1501636Notes

Reaction equation

HRID 1501636 reaction equation
Br[C:2]1[CH:3]=[C:4]([C:16]([NH:18][CH2:19][C:20]2[C:21](=[O:28])[NH:22][C:23]([CH3:27])=[CH:24][C:25]=2[CH3:26])=[O:17])[C:5]2[C:10]([CH2:11][CH3:12])=[N:9][N:8]([CH:13]([CH3:15])[CH3:14])[C:6]=2[N:7]=1.[CH3:29][C:30]1([CH3:47])[CH2:35][C:34](B2OC(C)(C)C(C)(C)O2)=[CH:33][C:32]([CH3:46])([CH3:45])[NH:31]1.C([O-])([O-])=O.[Na+].[Na+].CO.C(Cl)Cl>O1CCOCC1.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH3:26][C:25]1[CH:24]=[C:23]([CH3:27])[NH:22][C:21](=[O:28])[C:20]=1[CH2:19][NH:18][C:16]([C:4]1[C:5]2[C:10]([CH2:11][CH3:12])=[N:9][N:8]([CH:13]([CH3:15])[CH3:14])[C:6]=2[N:7]=[C:2]([C:34]2[CH2:33][C:32]([CH3:46])([CH3:45])[NH:31][C:30]([CH3:47])([CH3:29])[CH:35]=2)[CH:3]=1)=[O:17]

Participants

7

Reactant 4

HCID 10340Sodium CarbonateHCID 21226129Dichloromethane methanolHCID 467380232,2,6,6-Tetramethyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,2,3,6-tetrahydropyridineHCID 86703434HCID 86703434, compound

Product 1

HCID 68294930HCID 68294930, compoundYield 59%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

A solution of 6-bromo-N-((4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-3-ethyl-1-isopropyl-1H-pyrazolo[3,4-b]pyridine-4-carboxamide (0.15 g, 0.336 mmol), 2,2,6,6-tetramethyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,2,3,6-tetrahydropyridine (0.106 g, 0.403 mmol) and Pd(PPh3)4 (0.020 g, 0.017 mmol) in 1,4-dioxane (3 mL) was purged with argon for 10 min. Then, 2M Na2CO3 solution (0.128 g, 1.21 mmol) was added to it and again argon was purged through it for 10 min. The reaction mixture was stirred at 100° C. for 1 h. After completion of the reaction, water was added to it and extraction was carried out using 10% MeOH/DCM. The combined organic layers were washed with water, dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure to afford crude material which was purified by column chromatography to give the desired compound (59% yield). LCMS: 505.30 (M+1)+; HPLC: 99.84% (@ 254 nm) (Rt; 5.386); 1H NMR (DMSO-d6, 400 MHz) δ 11.49 (s, 1H), 8.68 (t, 1H), 7.32 (s, 1H), 6.72 (s, 1H), 5.88 (s, 1H), 5.17-5.10 (m, 1H), 4.33 (d, 2H, J=4.4 Hz), 2.84-2.79 (q, 2H, J=7.6 Hz), 2.39 (s, 2H), 2.25 (s, 3H), 2.11 (s, 3H), 1.46 (d, 6H, J=6.8 Hz), 1.22 (s, 6H), 1.13 (s, 6H), 1.06 (t, 3H, J=7.6 Hz).

Workup

  1. customwas purged through it for 10 min
  2. customAfter completion of the reaction, water
  3. additionwas added to it and extraction
  4. washThe combined organic layers were washed with water
  5. dry with materialdried over anhydrous Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customto afford crude material which
  9. customwas purified by column chromatography

Sources & evidence

ORD record
ord-fc555c03ee654b039182c3d0a8e32937
Source dataset
uspto-grants-2015_12
Patent number
US09206157B2

Reaction notes

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