Potassium Phosphate, Tribasic → HCID 118071191, compound

HRID 920839Notes

Reaction equation

HRID 920839 reaction equation
[C:1]([C:4]1[C:5](I)=[N:6][N:7]2[CH2:12][C:11]3([CH2:14][CH2:13]3)[N:10]([C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[CH2:9][C:8]=12)(=[O:3])[NH2:2].[O-]P([O-])([O-])=O.[K+].[K+].[K+].[Cl:31][C:32]1[CH:33]=[C:34](B(O)O)[CH:35]=[CH:36][C:37]=1[F:38]>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:34]2[CH:35]=[CH:36][C:37]([F:38])=[C:32]([Cl:31])[CH:33]=2)=[N:6][N:7]2[CH2:12][C:11]3([CH2:14][CH2:13]3)[N:10]([C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[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 118071140HCID 118071140, compound

Product 1

HCID 118071191HCID 118071191, compoundYield 72.1%

Reagents, catalysts & solvents 3

HCID 178418807HCID 178418807, compoundCatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
80 °C

Procedure

To a stirred suspension of Intermediate 350F (0.400 g, 0.956 mmol) in 1,4-dioxane (5 mL) was added K3PO4 (0.500 g, 2.80 mmol), (3-chloro-4-fluorophenyl) boronic acid (0.250 g, 1.435 mmol) and the reaction mixture was purged with nitrogen for 10 min. PdCl2(dppf)-CH2Cl2 (0.047 g, 0.057 mmol) was then added and the reaction mixture was heated to 80° C. and stirred for 12 h. The reaction mixture was diluted with water (25 mL) and extracted with EtOAc (3×25 mL) The combined organic layers were washed with brine, dried over Na2SO4, filtered and the filtrate concentrated. The crude product was purified by silica gel chromatography (24 g REDISEP® column, eluting with 3% MeOH in CHCl3). Fractions containing the product were combined and evaporated to afford Intermediate 350G as a pale yellow solid (0.29 g, 70%). MS(ES): m/z=421 [M+H]+; 1H NMR (400 MHz, chloroform-d) δ ppm 7.69 (dd, J=7.0, 2.3 Hz, 1H), 7.50 (ddd, J=8.5, 4.6, 2.1 Hz, 1H), 7.33-7.15 (m, 1H), 5.34 (br. s., 2H), 4.97 (br. s., 2H), 4.05 (br. s., 2H), 1.44 (s, 9H), 1.22-1.24 (m, 2H), 1.02-0.79 (m, 2H).

Workup

  1. customthe reaction mixture was purged with nitrogen for 10 min
  2. extractionextracted with EtOAc (3×25 mL) The combined organic layers
  3. washwere washed with brine
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationthe filtrate concentrated
  7. customThe crude product was purified by silica gel chromatography (24 g REDISEP® column, eluting with 3% MeOH in CHCl3)
  8. additionFractions containing the product
  9. customevaporated

Sources & evidence

ORD record
ord-7139ae2db4c1440da9ebea02d746836f
Source dataset
uspto-grants-2016_03
Patent number
US09273058B2

Reaction notes

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