Potassium Phosphate, Tribasic → HCID 131734891, compound

HRID 920821Notes

Reaction equation

HRID 920821 reaction equation
[C:1]([C:4]1[C:5]([I:21])=[N:6][N:7]2[CH2:12][CH:11]([CH3:13])[N:10]([C:14]([O:16][C:17]([CH3:20])(C)C)=[O:15])[CH2:9][C:8]=12)(=[O:3])[NH2:2].Cl[C:23]1C=C(B(O)O)C=C[C:28]=1F.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>O1CCOCC1.C(OCC)(=O)C.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].C(Cl)Cl>[C:1]([C:4]1[C:5]([I:21])=[N:6][N:7]2[CH2:12][CH:11]([CH3:13])[N:10]([C:14]([O:16][CH2:17][CH2:20][CH2:23][CH3:28])=[O:15])[CH2:9][C:8]=12)(=[O:3])[NH2:2]

Participants

7

Reactant 3

HCID 62657Potassium Phosphate, TribasicHCID 27346603-Chloro-4-fluorophenylboronic Acid (contains varying amounts of Anhydride)HCID 118071203HCID 118071203, compound

Product 1

HCID 131734891HCID 131734891, compoundYield 84.3%

Reagents, catalysts & solvents 3

HCID 178418807HCID 178418807, compoundCatalystHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
80 °C

Procedure

To a stirred suspension of Intermediate 340F (0.32 g, 0.788 mmol) in 1,4-dioxane (8.0 mL) was added (3-chloro-4-fluorophenyl)boronic acid (0.179 g, 1.024 mmol), K3PO4 (1.292 g, 2.58 mmol) and the contents of the flask were purged with N2 for 10 min. PdCl2(dppf)-CH2Cl2 (0.042 g, 0.052 mmol) was then added and the reaction mixture was stirred at 80° C. for 6 h. The reaction mixture was cooled to RT; diluted with ethyl acetate (10 mL), washed with water, dried over Na2SO4, filtered and the filtrate concentrated under reduced pressure. The crude compound was purified by silica gel chromatography (12 g REDISEP® column, eluting with 2% MeOH in CHCl3). Fractions containing the product were combined and evaporated to afford Intermediate 340G as a pale yellow solid (0.27 g, 84%). MS(ES): m/z=408 [M+H]+; 1H NMR (300 MHz, DMSO-d6) δ ppm 7.85-7.92 (m, 1H), 7.71 (ddd, J=8.69, 4.91, 2.27 Hz, 1H), 7.46 (d, J=17.75 Hz, 1H), 7.24-7.38 (m, 2H), 4.99 (d, J=17.75 Hz, 1H), 4.72 (br. s., 1H), 4.44 (d, J=17.75 Hz, 1H), 4.08-4.28 (m, 2H), 1.46 (s, 9H), 1.15 (s, 3H).

Workup

  1. customthe contents of the flask were purged with N2 for 10 min
  2. temperatureThe reaction mixture was cooled to RT
  3. washwashed with water
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationthe filtrate concentrated under reduced pressure
  7. customThe crude compound was purified by silica gel chromatography (12 g REDISEP® column, eluting with 2% MeOH in CHCl3)
  8. additionFractions containing the product
  9. customevaporated

Sources & evidence

ORD record
ord-0cb1c8e94c034a6bb51ee24d5d659c50
Source dataset
uspto-grants-2016_03
Patent number
US09273058B2

Reaction notes

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