Potassium Phosphate, Tribasic → HCID 118071161, compound

HRID 920723Notes

Reaction equation

HRID 920723 reaction equation
[C:1]([C:4]1[C:5](I)=[N:6][N:7]2[CH2:12][CH2:11][N:10]([C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])[CH2:9][C:8]=12)(=[O:3])[NH2:2].[Cl:21][C:22]1[CH:23]=[C:24](B(O)O)[CH:25]=[CH:26][C:27]=1[F:28].[O-]P([O-])([O-])=O.[K+].[K+].[K+]>O1CCOCC1.O.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]([C:24]2[CH:25]=[CH:26][C:27]([F:28])=[C:22]([Cl:21])[CH:23]=2)=[N:6][N:7]2[CH2:12][CH2:11][N:10]([C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])[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 118071150HCID 118071150, compound

Product 1

HCID 118071161HCID 118071161, compoundYield 83.8%

Reagents, catalysts & solvents 3

HCID 178418807HCID 178418807, compoundCatalystHCID 962WaterSolvent2×HCID 312751,4-DioxaneSolvent

Conditions

Temperature
80 °C

Procedure

To a stirred solution of Intermediate 156C (5 g, 12.7 mmol), (3-chloro-4-fluorophenyl)boronic acid (3.33 g, 19.12 mmol) in 1,4-dioxane (75 mL) and water (7.5 mL) was added and K3PO4 (8.12 g, 38.2 mmol) and the reaction mixture was purged with nitrogen for 5 min PdCl2(dppf)-CH2Cl2 (0.521 g, 0.637 mmol) was added and the reaction mixture was stirred at 80° C. for 12 h. The reaction mixture was diluted with water (75 mL) and extracted with EtOAc (3×75 mL). The combined organic layer was washed with brine, dried over Na2SO4, filtered and the filtrate concentrated. The crude reaction mixture was purified by silica gel chromatography (24 g REDISEP® column, eluting with 2% MeOH in CHCl3). Fractions were collected and concentrated to afford Intermediate 185A (4.2 g, 78%) as white solid. MS(ES): m/z=395 [M+H]+; 1H NMR 1H NMR (300 MHz, DMSO-d6) δ ppm 7.81-7.87 (m, 1H), 7.63-7.72 (m, 1H), 7.47 (s, 1H), 7.15-7.37 (m, 2H), 4.74 (s, 2H), 4.16 (s, 2H), 3.80-3.88 (m, 2H), 1.45 (s, 9H).

Workup

  1. additionwas added
  2. extractionextracted with EtOAc (3×75 mL)
  3. washThe combined organic layer was washed with brine
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationthe filtrate concentrated
  7. customThe crude reaction mixture
  8. customwas purified by silica gel chromatography (24 g REDISEP® column, eluting with 2% MeOH in CHCl3)
  9. customFractions were collected
  10. concentrationconcentrated

Sources & evidence

ORD record
ord-e70c2f3217c249f890897105b8f4fec7
Source dataset
uspto-grants-2016_03
Patent number
US09273058B2

Reaction notes

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