Potassium Phosphate, Tribasic → HCID 68291057, compound

HRID 1408967Notes

Reaction equation

HRID 1408967 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:9]([NH:10][C@@H:11]3[CH2:15][CH2:14][C@:13]([CH3:20])([C:16]([O:18][CH3:19])=[O:17])[C:12]3([CH3:22])[CH3:21])=[C:8]([C:23](=[O:25])[NH2:24])[CH:7]=[N:6][N:5]2[CH:26]=1.[C:27]1(B(O)O)[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>CN(C=O)C.C(P(C(C)(C)C)[C-]1C=CC=C1)(C)(C)C.[C-]1(P(C(C)(C)C)C(C)(C)C)C=CC=C1.[Fe+2].C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[C:23]([C:8]1[CH:7]=[N:6][N:5]2[CH:26]=[C:2]([C:27]3[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=3)[CH:3]=[C:4]2[C:9]=1[NH:10][C@@H:11]1[CH2:15][CH2:14][C@:13]([CH3:20])([C:16]([O:18][CH3:19])=[O:17])[C:12]1([CH3:21])[CH3:22])(=[O:25])[NH2:24]

Participants

7

Reactant 3

HCID 62657Potassium Phosphate, TribasicHCID 66827Phenylboronic AcidHCID 68358957HCID 68358957, compound

Product 1

HCID 68291057HCID 68291057, compoundYield 59.7%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 12976736Bis(ditert-butyl(cyclopenta-2,4-dien-1-yl)phosphane);iron(2+)CatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
90 °C

Procedure

A solution of (1S,3R)-methyl 3-(6-bromo-3-carbamoylpyrrolo[1,2-b]pyridazin-4-ylamino)-1,2,2-trimethylcyclopentanecarboxylate (307 mg, 0.725 mmol) in DMF (4.8 ml) was added into a reaction vial charged with phenylboronic acid (177 mg, 1.450 mmol), 1,1′-bis(di-tert-butylphosphino)ferrocene (34.8 mg, 0.073 mmol) and palladium (II) acetate (16.28 mg, 0.073 mmol), followed by addition of a 2.0 M aqueous potassium phosphate, dibasic solution (1.1 ml, 2.176 mmol). The suspension was purged with nitrogen for 5 minutes. The vial was sealed and heated at 90° C. for 2 hrs. The reaction was cooled to room temperature and diluted with ethyl acetate (20 ml). The ethyl acetate solution was washed with water (3×10 ml), dried with sodium sulfate, filtered, and concentrated under reduced pressure to give a light yellow oil. The crude product was chromatographed on the silica gel column eluted with 0-50% ethyl acetate in hexane, yielding the title compound (182 mg, 0.433 mmol, 59.7% yield) as a white solid. LC/MS found [M+H]+=420.9.

Workup

  1. customThe suspension was purged with nitrogen for 5 minutes
  2. customThe vial was sealed
  3. temperatureThe reaction was cooled to room temperature
  4. additiondiluted with ethyl acetate (20 ml)
  5. washThe ethyl acetate solution was washed with water (3×10 ml)
  6. dry with materialdried with sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customto give a light yellow oil
  10. customThe crude product was chromatographed on the silica gel column
  11. washeluted with 0-50% ethyl acetate in hexane

Sources & evidence

ORD record
ord-82aaf8a314d2448e87e9ead386b4dd7e
Source dataset
uspto-grants-2014_12
Patent number
US08921368B2

Reaction notes

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