Potassium Phosphate, Tribasic → HCID 86714734, compound

HRID 2171838Notes

Reaction equation

HRID 2171838 reaction equation
Cl[C:2]1[N:7]=[C:6]([NH:8][C@@H:9]([C:22]([CH3:25])([CH3:24])[CH3:23])/[CH:10]=[CH:11]/[P:12](=[O:21])([O:17][CH:18]([CH3:20])[CH3:19])[O:13][CH:14]([CH3:16])[CH3:15])[C:5]([F:26])=[CH:4][N:3]=1.[F:27][C:28]1[CH:29]=[C:30]2[C:36](B3OC(C)(C)C(C)(C)O3)=[CH:35][N:34]([S:46]([C:49]3[CH:54]=[CH:53][C:52]([CH3:55])=[CH:51][CH:50]=3)(=[O:48])=[O:47])[C:31]2=[N:32][CH:33]=1.[O-]P([O-])([O-])=O.[K+].[K+].[K+].CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C>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].O>[F:26][C:5]1[C:6]([NH:8][C@@H:9]([C:22]([CH3:25])([CH3:24])[CH3:23])/[CH:10]=[CH:11]/[P:12](=[O:21])([O:17][CH:18]([CH3:20])[CH3:19])[O:13][CH:14]([CH3:16])[CH3:15])=[N:7][C:2]([C:36]2[C:30]3[C:31](=[N:32][CH:33]=[C:28]([F:27])[CH:29]=3)[N:34]([S:46]([C:49]3[CH:54]=[CH:53][C:52]([CH3:55])=[CH:51][CH:50]=3)(=[O:47])=[O:48])[CH:35]=2)=[N:3][CH:4]=1

Participants

7

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 86714735HCID 86714735, compound2×

Product 1

HCID 86714734HCID 86714734, compound

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 962WaterSolvent

Conditions

Temperature
100 °C

Procedure

To a solution of (R,E)-diisopropyl (3-((2-chloro-5-fluoropyrimidin-4-yl)amino)-4,4-dimethylpent-1-en-1-yl)phosphonate, 16a, (0.81 g, 1.99 mmol) and 5-fluoro-1-(p-tolylsulfonyl)-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrrolo[2,3-b]pyridine, 7a, (1.24 g, 3.00 mmol) in 2-Me-THF (16 mL) was added K3PO4 (1.27 g, 3.00 mmol) and water (4 mL). The biphasic mixture was degassed under a stream of nitrogen for 15 minutes. Then, X-Phos (0.11 g, 0.24 mmol) and Pd2(dba)3 (0.06 g, 0.06 mmol) was added to the mixture. After degassing with nitrogen for an additional 5 minutes, the vessel was sealed and heated at 100° C. for 2 hours. The mixture was cooled to room temperature and diluted with EtOAc, filtered through celite. The filtrate was washed with brine, dried (MgSO4), filtered and concentrated in vacuo. The crude residue was purified via silica gel chromatography (0-50% EtOAc/CH2Cl2 gradient) to afford 1.123 g of the desired product: 1H NMR (400 MHz, d6-DMSO) δ 8.55-8.42 (m, 3H), 8.31 (d, J=3.7 Hz, 1H), 8.06 (d, J=8.3 Hz, 2H), 7.73 (d, J=8.9 Hz, 1H), 7.44 (d, J=8.4 Hz, 2H), 6.80 (ddd, J=22.2, 17.1, 6.9 Hz, 1H), 5.99 (dd, J=20.3, 17.1 Hz, 1H), 4.95 (t, J=7.6 Hz, 1H), 4.51-4.32 (m, 2H), 2.35 (s, 3H), 1.19-1.14 (m, 6H), 1.11 (dd, J=6.0, 4.4 Hz, 6H), 1.02 (s, 9H).); LCMS Gradient 10-90%, 0.1% formic acid, 5 minutes, C18/ACN, RT=4.06 minutes (M+H) 662.35.

Workup

  1. customThe biphasic mixture was degassed under a stream of nitrogen for 15 minutes
  2. customAfter degassing with nitrogen for an additional 5 minutes
  3. customthe vessel was sealed
  4. temperatureThe mixture was cooled to room temperature
  5. additiondiluted with EtOAc
  6. filtrationfiltered through celite
  7. washThe filtrate was washed with brine
  8. dry with materialdried (MgSO4)
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo
  11. customThe crude residue was purified via silica gel chromatography (0-50% EtOAc/CH2Cl2 gradient)

Sources & evidence

ORD record
ord-6f53bc6779cf4672b9f7f02091c8aa16
Source dataset
uspto-grants-2015_06
Patent number
US09051319B2

Reaction notes

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