Sodium Carbonate → HCID 68350869, compound

HRID 1909249Notes

Reaction equation

HRID 1909249 reaction equation
Br[C:2]1[CH:3]=[C:4]([C:14]([NH:16][CH2:17][C:18]2[C:19](=[O:28])[NH:20][C:21]([CH3:27])=[CH:22][C:23]=2[CH2:24][O:25][CH3:26])=[O:15])[C:5]2[CH:10]=[N:9][N:8]([CH:11]([CH3:13])[CH3:12])[C:6]=2[N:7]=1.[CH3:29][C:30]1([CH3:41])[CH2:35][C:34](B(O)O)=[CH:33][C:32]([CH3:40])([CH3:39])[NH:31]1.C([O-])([O-])=O.[Na+].[Na+]>O1CCOCC1.O.O.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>[CH:11]([N:8]1[C:6]2[N:7]=[C:2]([C:34]3[CH2:33][C:32]([CH3:40])([CH3:39])[NH:31][C:30]([CH3:41])([CH3:29])[CH:35]=3)[CH:3]=[C:4]([C:14]([NH:16][CH2:17][C:18]3[C:19](=[O:28])[NH:20][C:21]([CH3:27])=[CH:22][C:23]=3[CH2:24][O:25][CH3:26])=[O:15])[C:5]=2[CH:10]=[N:9]1)([CH3:13])[CH3:12]

Participants

7

Reactant 3

HCID 10340Sodium CarbonateHCID 68295292HCID 68295292, compoundHCID 86703429HCID 86703429, compound

Product 1

HCID 68350869HCID 68350869, compoundYield 44%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 218864351,4-Dioxane--water (1/1)Solvent

Conditions

Temperature
100 °C

Procedure

To a stirred solution of 6-bromo-1-isopropyl-N-((4-(methoxymethyl)-6-methyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-1H-pyrazolo[3,4-b]pyridine-4-carboxamide (0.06 g, 0.133 mmol) and (2,2,6,6-tetramethyl-1,2,3,6-tetrahydropyridin-4-yl)boronic acid (0.043 g, 0.160 mmol) in dioxane/water mixture (1.5 mL+0.5 mL), Na2CO3 (0.5 g, 0.5 mmol) was added and solution purged with argon for 15 min. Then Pd(PPh3)4 (0.008 g, 0.007 mmol) was added and argon was purged again for 10 min Reaction mass was heated at 100° C. for 2 h. On completion, reaction mixture was diluted with water and extracted with 10% MeOH/DCM. Combined organic layers were dried over Na2SO4 and solvent removed under reduced pressure to obtain crude material which was purified by column chromatography over silica gel to afford the desired product (44% yield). LCMS: 507.25 (M+1)+; HPLC: 99.64% (@ 254 nm) (Rt;5.159); 1H NMR (DMSO-d6, 400 MHz) δ 11.68 (bs, 1H), 8.91 (t, 1H), 8.26 (s, 1H), 7.77 (s, 1H), 6.80 (s, 1H), 6.09 (s, 1H), 5.24-5.18 (m, 1H), 4.51 (s, 2H), 4.35 (d, 2H, J=4.4 Hz), 3.32 (3H merged in DMSO peak), 2.43 (s, 2H), 2.17 (s, 3H), 1.49 (d, 6H, J=6 Hz), 1.24 (s, 6H), 1.14 (s, 6H).

Workup

  1. customsolution purged with argon for 15 min
  2. customargon was purged again for 10 min
  3. customReaction mass
  4. customOn completion, reaction mixture
  5. extractionextracted with 10% MeOH/DCM
  6. dry with materialCombined organic layers were dried over Na2SO4 and solvent
  7. customremoved under reduced pressure
  8. customto obtain crude material which
  9. customwas purified by column chromatography over silica gel

Sources & evidence

ORD record
ord-77b184cb58bb4d2a976390dd7b85c15e
Source dataset
uspto-grants-2013_12
Patent number
US08598167B1

Reaction notes

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