Potassium Phosphate, Tribasic → HCID 68007534, compound

HRID 527093Notes

Reaction equation

HRID 527093 reaction equation
[O-]P([O-])([O-])=O.[K+].[K+].[K+].Cl[C:10]1[N:15]=[C:14]([NH:16][C@H:17]2[CH2:22][CH2:21][CH2:20][C@@H:19]([OH:23])[CH2:18]2)[C:13]([F:24])=[CH:12][N:11]=1.[F:25][C:26]1[CH:27]=[C:28]2[C:34](B3OC(C)(C)C(C)(C)O3)=[CH:33][N:32]([S:44]([C:47]3[CH:53]=[CH:52][C:50]([CH3:51])=[CH:49][CH:48]=3)(=[O:46])=[O:45])[C:29]2=[N:30][CH:31]=1.CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C>O.[Cl-].[Na+].O.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].C(OCC)(=O)C>[F:24][C:13]1[C:14]([NH:16][C@H:17]2[CH2:22][CH2:21][CH2:20][C@@H:19]([OH:23])[CH2:18]2)=[N:15][C:10]([C:34]2[C:28]3[C:29](=[N:30][CH:31]=[C:26]([F:25])[CH:27]=3)[N:32]([S:44]([C:47]3[CH:53]=[CH:52][C:50]([CH3:51])=[CH:49][CH:48]=3)(=[O:45])=[O:46])[CH:33]=2)=[N:11][CH:12]=1

Participants

9

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 672856905-fluoro-1-((4-methylphenyl)sulfonyl)-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrrolo(2,3-b)pyridineHCID 86667455HCID 86667455, compound2×

Product 1

HCID 68007534HCID 68007534, compound

Reagents, catalysts & solvents 4

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 962WaterSolventHCID 8857Ethyl AcetateSolventHCID 57417360Sodium chloride; waterSolvent

Conditions

Temperature
70 °C

Procedure

K3PO4 (2.59 g, 12.21 mmol) in water (6 mL) and 2-Me-THF (20 mL) was purged with a flow of nitrogen for 30 min. Added (1R,3S)-3-[(2-chloro-5-fluoro-pyrimidin-4-yl)amino]cyclohexanol, 75a, (1.00 g, 4.07 mmol) and 5-fluoro-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1-tosyl-1H-pyrrolo[2,3-b]pyridine, 44a, (2.03 g, 4.88 mmol) and then purged with nitrogen for another 15 min. The reaction was then heated to 70° C. and then charged with Tris(dibenzylideneacetone)dipalladium (0.07 g, 0.08 mmol) and X-Phos (0.14 g, 0.28 mmol) under nitrogen. (Note Color changed from purple to hunter green). The reaction was heated to reflux for 1 h and 20 min. The reaction was cooled slowly to room temperature overnight. The mixture was treated with 100 mL of brine and 100 mL of ethyl acetate and separated the two layers. The aqueous phase was extracted again with EtOAc (50 mL). Combined organic layers and passed through a plug of fluoracil, dried over Na2SO4, decanted and removed the solvent by rotoevaporation to give crude product which was then purified by silica gel chromatography (25-50% EtOAc/Hexanes) to afford the desired product.

Workup

  1. temperatureThe reaction was heated
  2. temperatureto reflux for 1 h and 20 min
  3. temperatureThe reaction was cooled slowly to room temperature overnight
  4. customseparated the two layers
  5. extractionThe aqueous phase was extracted again with EtOAc (50 mL)
  6. dry with materialdried over Na2SO4
  7. customdecanted
  8. customremoved the solvent by rotoevaporation
  9. customto give crude product which
  10. customwas then purified by silica gel chromatography (25-50% EtOAc/Hexanes)

Sources & evidence

ORD record
ord-596cb3b8bf3b4edd89a891a3b7403d8b
Source dataset
uspto-grants-2016_05
Patent number
US09345708B2

Reaction notes

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