Potassium Phosphate, Tribasic → HCID 67457983, compound

HRID 1853069Notes

Reaction equation

HRID 1853069 reaction equation
Cl[C:2]1[N:7]=[C:6]([C:8]2[CH:9]=[N:10][N:11]([C:13]3([CH2:24][C:25]#[N:26])[CH2:16][N:15]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[CH2:14]3)[CH:12]=2)[N:5]2[CH:27]=[CH:28][N:29]=[C:4]2[CH:3]=1.[CH:30]1(B(O)O)[CH2:32][CH2:31]1.CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C.COC1C=CC=C(OC)C=1C1C=CC=CC=1P(C1CCCCC1)C1CCCCC1.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:25]([CH2:24][C:13]1([N:11]2[CH:12]=[C:8]([C:6]3[N:5]4[CH:27]=[CH:28][N:29]=[C:4]4[CH:3]=[C:2]([CH:30]4[CH2:32][CH2:31]4)[N:7]=3)[CH:9]=[N:10]2)[CH2:16][N:15]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[CH2:14]1)#[N:26]

Participants

8

Reactant 5

HCID 62657Potassium Phosphate, TribasicHCID 2760897Cyclopropylboronic acidHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 112698722-Dicyclohexylphosphino-2',6'-dimethoxybiphenylHCID 86685321HCID 86685321, compound

Product 1

HCID 67457983HCID 67457983, compound

Reagents, catalysts & solvents 2

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

Conditions

Temperature
75 °C

Procedure

To a vial were added tert-butyl 3-(4-(7-chloroimidazo[1,2-c]pyrimidin-5-yl)-1H-pyrazol-1-yl)-3-(cyanomethyl)azetidine-1-carboxylate (Preparation N; 400 mg; 0.967 mmol), cyclopropylboronic acid (830 mg; 9.67 mmol), Pd2dba3 (177 mg; 0.193 mmol), XPHOS (92 mg; 0.913 mmol), S-Phos (79 mg; 0.913 mmol), potassium phosphate (3.87 mmol; 2M aqueous solution) and 1,4-dioxane (10 mL). The mixture was sparged with nitrogen for 15 minutes and the vial was sealed. The mixture was heated at 75° C. with stirring for 6 hours. The mixture was allowed to cool and diluted with methylene chloride (30 mL). Aqueous sodium bicarbonate solution (20 mL) was added. The phases were separated and the aqueous phase was extracted into methylene chloride (2×30 mL). The combined organic phases were dried (magnesium sulfate), filtered and concentrated under reduced pressure.

Workup

  1. customThe mixture was sparged with nitrogen for 15 minutes
  2. customthe vial was sealed
  3. temperatureto cool
  4. additiondiluted with methylene chloride (30 mL)
  5. additionAqueous sodium bicarbonate solution (20 mL) was added
  6. customThe phases were separated
  7. extractionthe aqueous phase was extracted into methylene chloride (2×30 mL)
  8. dry with materialThe combined organic phases were dried (magnesium sulfate)
  9. filtrationfiltered
  10. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-b7caa69a99a54f7e927f14f1b2f9e89c
Source dataset
uspto-grants-2015_02
Patent number
US08962596B2

Reaction notes

Loading…