HCID 90403622, compound → HCID 86268465, compound

HRID 1049333Notes

Reaction equation

HRID 1049333 reaction equation
Cl[C:2]1[CH:7]=[C:6]([O:8][C:9]2[CH:10]=[CH:11][C:12]([NH:16][C:17]([NH:19][C:20](=[O:25])[C:21]([CH3:24])([CH3:23])[CH3:22])=[O:18])=[N:13][C:14]=2[CH3:15])[CH:5]=[CH:4][N:3]=1>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>[CH3:15][C:14]1[N:13]=[C:12]([NH:16][C:17]([NH:19][C:20](=[O:25])[C:21]([CH3:24])([CH3:23])[CH3:22])=[O:18])[CH:11]=[CH:10][C:9]=1[O:8][C:6]1[CH:5]=[CH:4][N:3]=[C:2]([C:11]2[CH:12]=[N:13][C:14]([CH3:15])=[CH:9][CH:10]=2)[CH:7]=1

Participants

3

Reactant 1

HCID 90403622HCID 90403622, compound

Product 1

HCID 86268465HCID 86268465, compoundYield 129.8%

Reagents, catalysts & solvents 1

HCID 178418397HCID 178418397, compoundCatalyst

Conditions

Temperature
80 °C

Procedure

A suspension of Example C1 (0.20 g, 0.551 mmol), Example C2 (0.254 g, 1.158 mmol) and satd. NaHCO3 (1.1 mL) in dioxane (4.4 mL) was sparged with Ar under sonication, treated with Pd(PPh3)4 (0.064 g, 0.055 mmol), sparged again with Ar, heated at 80° C. for 3 h, then 90° C. for 1.5 h. The mixture was cooled to RT, diluted with EtOAc and filtered through diatomaceous earth. The filtrate was concentrated to dryness and purified via silica gel chromatography (MeOH/DCM). The material was further purified via reverse-phase silica gel chromatography (MeCN/H2O with 0.1% TFA). Pure fractions were combined and concentrated under reduced pressure. The aqueous residue was neutralized with satd. Na2CO3 and the solid collected via filtration, dissolved in MeCN/H2O, frozen and lyophilized to afford N-((6-methyl-5-((6′-methyl-[2,3′-bipyridin]-4-yl)oxy)pyridin-2-yl)carbamoyl)pivalamide (150 mg, 65%) as a white solid. 1H NMR (400 MHz, DMSO-d6): δ 11.15 (s, 1H), 10.39 (s, 1H), 9.08 (d, J=2.4 Hz, 1H), 8.52 (d, J=5.7 Hz, 1H), 8.26 (dd, J=8.1, 2.4 Hz, 1H), 7.91 (m, 1H), 7.65 (d, J=8.8 Hz, 1H), 7.57 (d, J=2.4 Hz, 1H), 7.32 (d, J=8.2 Hz, 1H), 6.78 (dd, J=5.7, 2.4 Hz, 1H), 2.49 (s, 3H), 2.26 (s, 3H), 1.20 (s, 9H); MS (ESI) m/z: 420.2 (M+H+).

Workup

  1. customNaHCO3 (1.1 mL) in dioxane (4.4 mL) was sparged with Ar under sonication
  2. customsparged again with Ar
  3. temperatureThe mixture was cooled to RT
  4. additiondiluted with EtOAc
  5. filtrationfiltered through diatomaceous earth
  6. concentrationThe filtrate was concentrated to dryness
  7. custompurified via silica gel chromatography (MeOH/DCM)
  8. customThe material was further purified via reverse-phase silica gel chromatography (MeCN/H2O with 0.1% TFA)
  9. concentrationconcentrated under reduced pressure
  10. filtrationNa2CO3 and the solid collected via filtration
  11. dissolutiondissolved in MeCN/H2O
  12. temperaturefrozen

Sources & evidence

ORD record
ord-dfc2bb699e814ebdbc0a416061867b61
Source dataset
uspto-grants-2016_07
Patent number
US09382228B2

Reaction notes

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