Sodium Bicarbonate → HCID 90403797, compound

HRID 1049358Notes

Reaction equation

HRID 1049358 reaction equation
Cl[C:2]1[CH:7]=[C:6]([O:8][C:9]2[CH:10]=[CH:11][C:12]([NH:15][C:16]([NH:18][C:19]([CH:21]3[CH2:26][CH2:25][O:24][CH2:23][CH2:22]3)=[O:20])=[O:17])=[N:13][CH:14]=2)[CH:5]=[CH:4][N:3]=1.C([O-])(O)=O.[Na+].[CH3:32][C:33]1[CH:38]=[CH:37][C:36](B2OC(C)(C)C(C)(C)O2)=[CH:35][N:34]=1>O1CCOCC1.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>[CH3:32][C:33]1[N:34]=[CH:35][C:36]([C:2]2[CH:7]=[C:6]([O:8][C:9]3[CH:10]=[CH:11][C:12]([NH:15][C:16]([NH:18][C:19]([CH:21]4[CH2:26][CH2:25][O:24][CH2:23][CH2:22]4)=[O:20])=[O:17])=[N:13][CH:14]=3)[CH:5]=[CH:4][N:3]=2)=[CH:37][CH:38]=1

Participants

7

Reactant 3

HCID 516892Sodium BicarbonateHCID 164142722-Methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridineHCID 90403384HCID 90403384, compound

Product 1

HCID 90403797HCID 90403797, compoundYield 13%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
95 °C

Procedure

A mixture of N-((5-((2-chloropyridin-4-yl)oxy)pyridin-2-yl)carbamoyl)tetrahydro-2H-pyran-4-carboxamide (0.334 g, 0.886 mmol), NaHCO3 (0.149 g, 1.773 mmol) and 2-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine (0.233 g, 1.064 mmol) in dioxane (4 mL) and water (1 mL) was sparged with Ar under sonication for 5 minutes, treated with Pd(PPh3)4 (0.102 g, 0.089 mmol), sparged again with Ar and heated at 95° C. overnight. The mixture was cooled to RT, diluted with THF and washed with brine. The aqueous layer was back-extracted with THF (3×) and the combined organics were dried over Na2SO4 and concentrated to dryness. The material was treated with MeCN and sonicated. The solids were collected via filtration and purified via silica gel chromatography (MeOH/EtOAc) to afford N-((5-((6′-methyl-[2,3′-bipyridin]-4-yl)oxy)pyridin-2-yl)carbamoyl)tetrahydro-2H-pyran-4-carboxamide (50 mg, 13%) as a white solid. 1H NMR (400 MHz, DMSO-d6): δ 11.06 (s, 1H), 10.88 (s, 1H), 9.10 (d, J=2.3 Hz, 1H), 8.55 (d, J=5.7 Hz, 1H), 8.30-8.26 (m, 2H), 8.09 (d, J=9.0 Hz, 1H), 7.76 (dd, J=9.0, 2.9 Hz, 1H), 7.63 (d, J=2.4 Hz, 1H), 7.33 (d, J=8.2 Hz, 1H), 6.89 (dd, J=5.7, 2.4 Hz, 1H), 3.91-3.85 (m, 2H), 3.33-3.26 (m, 2H), 2.73-2.64 (m, 1H), 2.50 (s, 3H), 1.75-1.68 (m, 2H), 1.67-1.56 (m, 2H); MS (ESI) m/z: 432.1 (M−H+).

Workup

  1. customwas sparged with Ar under sonication for 5 minutes
  2. customsparged again with Ar
  3. temperatureThe mixture was cooled to RT
  4. additiondiluted with THF
  5. washwashed with brine
  6. extractionThe aqueous layer was back-extracted with THF (3×)
  7. dry with materialthe combined organics were dried over Na2SO4
  8. concentrationconcentrated to dryness
  9. additionThe material was treated with MeCN
  10. customsonicated
  11. filtrationThe solids were collected via filtration
  12. custompurified via silica gel chromatography (MeOH/EtOAc)

Sources & evidence

ORD record
ord-7822fd0810624596a95e7dab56164857
Source dataset
uspto-grants-2016_07
Patent number
US09382228B2

Reaction notes

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