Potassium Phosphate, Tribasic → HCID 118071134, compound

HRID 920725Notes

Reaction equation

HRID 920725 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[Cl: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:25]2[CH:24]=[CH:23][C:22]([Cl:21])=[C:27]([Cl:28])[CH:26]=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 27343303,4-Dichlorobenzeneboronic acidHCID 118071150HCID 118071150, compound

Product 1

HCID 118071134HCID 118071134, compoundYield 85%

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 (9 g, 23 mmol), (3,4-dichlorophenyl) boronic acid (6.57 g, 34.4 mmol) in 1,4-dioxane (150 mL) and water (10 mL) was added K3PO4 (14.61 g, 68.8 mmol) and the reaction mixture was purged with nitrogen for 15 min. PdCl2(dppf)-CH2Cl2 (1.124 g, 1.377 mmol) was added and the reaction mixture was stirred at 80° C. for 12 h. The reaction mixture was diluted with water (300 mL) and extracted with EtOAc (3×80 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 (40 g REDISEP® column, eluting with 65% EtOAc in hexanes). Fractions were collected and concentrated to afford Intermediate 199A as pale yellow solid (8 g, 85%). MS(ES): m/z=411.0 [M+H]+; 1H NMR: (400 MHz, DMSO-d6) δ ppm 7.92-7.87 (m, 1H), 7.69-7.64 (m, 2H), 7.44-7.18 (m, 2H), 4.74 (s, 2H), 4.17 (t, 2H), 3.84 (t, 2H), 1.45 (s, 9H).

Workup

  1. customthe reaction mixture was purged with nitrogen for 15 min
  2. extractionextracted with EtOAc (3×80 mL) The combined organic layer
  3. washwas 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 (40 g REDISEP® column, eluting with 65% EtOAc in hexanes)
  9. customFractions were collected
  10. concentrationconcentrated

Sources & evidence

ORD record
ord-28dcc620c27e46f9b91564295d789136
Source dataset
uspto-grants-2016_03
Patent number
US09273058B2

Reaction notes

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