Potassium Phosphate, Tribasic → HCID 86729376, compound

HRID 521216Notes

Reaction equation

HRID 521216 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]([C:8]([OH:11])([CH3:10])[CH3:9])=[N:6][CH:7]=1.[NH2:12][C:13]1[C:17]([C:18](=[O:20])[NH2:19])=[CH:16][N:15]([C:21]2([CH2:35][C:36]#[N:37])[CH2:26][CH2:25][N:24]([C:27]([O:29][CH2:30][C:31]([F:34])([F:33])[F:32])=[O:28])[CH2:23][CH2:22]2)[N:14]=1.C(P(C(C)(C)C)C1C(C)=C(C)C(C)=C(C)C=1C1C(C(C)C)=CC(C(C)C)=CC=1C(C)C)(C)(C)C.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>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].O1CCOCC1>[C:18]([C:17]1[C:13]([NH:12][C:2]2[CH:7]=[N:6][C:5]([C:8]([OH:11])([CH3:10])[CH3:9])=[CH:4][CH:3]=2)=[N:14][N:15]([C:21]2([CH2:35][C:36]#[N:37])[CH2:26][CH2:25][N:24]([C:27]([O:29][CH2:30][C:31]([F:34])([F:33])[F:32])=[O:28])[CH2:23][CH2:22]2)[CH:16]=1)(=[O:20])[NH2:19]

Participants

7

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 11953610Di-tert-butyl[3,4,5,6-tetramethyl-2',4',6'-tris(propan-2-yl)-[1,1'-biphenyl]-2-yl]phosphaneHCID 154863922-(5-Bromopyridin-2-yl)propan-2-ol2×HCID 86729377HCID 86729377, compound2×

Product 1

HCID 86729376HCID 86729376, compound

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
90 °C

Procedure

2-(5-Bromopyridin-2-yl)propan-2-ol (Intermediate 5) (23 mg, 0.11 mmol), 2,2,2-trifluoroethyl 4-(3-amino-4-carbamoyl-1H-pyrazol-1-yl)-4-(cyanomethyl)piperidine-1-carboxylate (Intermediate 35-3) 40 mg, 0.11 mmol), Pd2(dba)3 (10 mg, 0.011 mmol), 2-di-t-butylphosphino-3,4,5,6-teramethyl-2′,4′,6′-triisopropylbiphenyl (15 mg, 0.032 mmol), potassium phosphate (45 mg, 0.21 mmol), and 1,4-dioxane (1.0 mL) were combined in a 4 mL vial. The vial was capped and flushed with argon. The mixture was heated to 90° C. and allowed to stir for 2 hours. The mixture was then cooled to ambient temperature, diluted with EtOAc, and washed sequentially with water and brine. The organic layer was dried over anhydrous MgSO4, filtered, and concentrated in vacuo. The residue was purified by MPLC on silica gel (using a gradient elution of 0-10% MeOH/DCM) to afford the title compound, Example #10-1.

Workup

  1. customThe vial was capped
  2. customflushed with argon
  3. temperatureThe mixture was then cooled to ambient temperature
  4. additiondiluted with EtOAc
  5. washwashed sequentially with water and brine
  6. dry with materialThe organic layer was dried over anhydrous MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customThe residue was purified by MPLC on silica gel (
  10. washa gradient elution of 0-10% MeOH/DCM)

Sources & evidence

ORD record
ord-d8d72af898094a46830b9449e4a4c908
Source dataset
uspto-grants-2016_05
Patent number
US09328099B2

Reaction notes

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