Potassium Phosphate, Tribasic → HCID 118071153, compound

HRID 920722Notes

Reaction equation

HRID 920722 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][CH:27]=1.[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:26]2[CH:25]=[CH:24][CH:23]=[C:22]([Cl:21])[CH:27]=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 2734323(3-Chlorophenyl)boronic acidHCID 118071150HCID 118071150, compound

Product 1

HCID 118071153HCID 118071153, compoundYield 79.1%

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 (500 mg, 1.275 mmol) and (3-chlorophenyl)boronic acid (399 mg, 2.55 mmol) in 1,4-dioxane (5 mL) and water (1 mL) was added and potassium phosphate tribasic (666 mg, 3.82 mmol). The reaction mixture was purged with nitrogen for 5 min. PdCl2(dppf)-CH2Cl2 (52.1 mg, 0.064 mmol) was added and the reaction mixture was stirred at 80° C. for 12 h. The reaction mixture was diluted with water (20 mL) and extracted with ethyl acetate (3×25 mL). The combined organic layer was washed with brine, dried over Na2SO4 and concentrated. The crude was purified by ISCO (24 g silica column) using 2% methanol in chloroform. Fractions were collected and concentrated to afford Intermediate 156D (380 mg, 79%). MS(ES): m/z 377 [M+H]+; 1H NMR (300 MHz, CDCl3) δ ppm 7.60 (s, 1H), 7.46 (m, 3H), 5.32 (bs, 2H), 4.97 (s, 2H), 4.21 (t, J=5.1 Hz, 2H), 3.94 (t, J=5.7 Hz, 2H), 1.29 (s, 9H).

Workup

  1. customThe reaction mixture was purged with nitrogen for 5 min
  2. extractionextracted with ethyl acetate (3×25 mL)
  3. washThe combined organic layer was washed with brine
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated
  6. customThe crude was purified by ISCO (24 g silica column)
  7. customFractions were collected
  8. concentrationconcentrated

Sources & evidence

ORD record
ord-6ff01d786e314c9dbd70668b8ddb8c1a
Source dataset
uspto-grants-2016_03
Patent number
US09273058B2

Reaction notes

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