Potassium Phosphate, Tribasic → (S)-tert-Butyl 2-(2-(5-fluoro-2-(5-fluoro-1-tosyl-1H-pyrrolo[2,3-b]pyridin-3-yl)pyrimidin-4-ylamino)-3,3-dimethylbutylsulfonyl)ethanoate

HRID 2171925Notes

Reaction equation

HRID 2171925 reaction equation
[F:1][C:2]1[CH:3]=[C:4]2[C:10](B3OC(C)(C)C(C)(C)O3)=[CH:9][N:8]([S:20]([C:23]3[CH:28]=[CH:27][C:26]([CH3:29])=[CH:25][CH:24]=3)(=[O:22])=[O:21])[C:5]2=[N:6][CH:7]=1.Cl[C:31]1[N:36]=[C:35]([NH:37][C@@H:38]([C:51]([CH3:54])([CH3:53])[CH3:52])[CH2:39][S:40]([CH2:43][C:44]([O:46][C:47]([CH3:50])([CH3:49])[CH3:48])=[O:45])(=[O:42])=[O:41])[C:34]([F:55])=[CH:33][N:32]=1.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>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].CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C>[F:55][C:34]1[C:35]([NH:37][C@@H:38]([C:51]([CH3:54])([CH3:53])[CH3:52])[CH2:39][S:40]([CH2:43][C:44]([O:46][C:47]([CH3:49])([CH3:48])[CH3:50])=[O:45])(=[O:42])=[O:41])=[N:36][C:31]([C:10]2[C:4]3[C:5](=[N:6][CH:7]=[C:2]([F:1])[CH:3]=3)[N:8]([S:20]([C:23]3[CH:24]=[CH:25][C:26]([CH3:29])=[CH:27][CH:28]=3)(=[O:21])=[O:22])[CH:9]=2)=[N:32][CH:33]=1

Participants

7

Reactant 3

HCID 62657Potassium Phosphate, TribasicHCID 672856905-fluoro-1-((4-methylphenyl)sulfonyl)-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrrolo(2,3-b)pyridine2×HCID 86714776(S)-tert-Butyl 2-(2-(2-chloro-5-fluoropyrimidin-4-ylamino)-3,3-dimethylbutyl-sulfonyl)ethanoate2×

Product 1

HCID 86714777(S)-tert-Butyl 2-(2-(5-fluoro-2-(5-fluoro-1-tosyl-1H-pyrrolo[2,3-b]pyridin-3-yl)pyrimidin-4-ylamino)-3,3-dimethylbutylsulfonyl)ethanoate

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylCatalystHCID 962WaterSolvent

Conditions

Temperature
115 °C

Procedure

A solution of 5-fluoro-1-(p-tolylsulfonyl)-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrrolo[2,3-b]pyridine, 7a, (0.76 g, 1.83 mmol), (S)-tert-Butyl 2-(2-(2-chloro-5-fluoropyrimidin-4-ylamino)-3,3-dimethylbutyl-sulfonyl)ethanoate, 169a, (0.75 g, 1.83 mmol) and K3PO4 (0.93 g, 4.39 mmol) in 2-methyl THF (10 mL) and water (2 mL) was degassed under a stream of nitrogen for 30 minutes. X-Phos (0.06 g, 0.12 mmol) and Pd2(dba)3 (0.03 g, 0.03 mmol) were added and the reaction mixture was heated at 115° C. in a pressure vial for 2.5 hours. The reaction mixture was cooled to room temperature, filtered and concentrated in vacuo. The residue was dissolved in EtOAc (50 mL) and washed with water. The organic layer was dried (MgSO4), filtered and concentrated in vacuo. The crude product was purified via silica gel chromatography (0-60% EtOAc/Hexanes gradient) to afford 1.0 g of the desired product as a foamy solid: LCMS Gradient 60-98% ACN/water, 0.9% formic acid, 7 minutes, C4, Retention Time=2.39 minutes (M+H) 564.34.

Workup

  1. temperatureThe reaction mixture was cooled to room temperature
  2. filtrationfiltered
  3. concentrationconcentrated in vacuo
  4. dissolutionThe residue was dissolved in EtOAc (50 mL)
  5. washwashed with water
  6. dry with materialThe organic layer was dried (MgSO4)
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customThe crude product was purified via silica gel chromatography (0-60% EtOAc/Hexanes gradient)

Sources & evidence

ORD record
ord-dd66091fd388426493dcd1c0b8b15907
Source dataset
uspto-grants-2015_06
Patent number
US09051319B2

Reaction notes

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