Potassium Phosphate, Tribasic → 3-Cyclopropyl-3-(4-(7-(1-(oxetan-3-yl)-1H-pyrazol-4-yl)imidazo[1,2-c]pyrimidin-5-yl)-1H-pyrazol-1-yl)propanenitrile

HRID 1852995Notes

Reaction equation

HRID 1852995 reaction equation
Cl[C:2]1[N:7]=[C:6]([C:8]2[CH:9]=[N:10][N:11]([CH:13]([CH:17]3[CH2:19][CH2:18]3)[CH2:14][C:15]#[N:16])[CH:12]=2)[N:5]2[CH:20]=[CH:21][N:22]=[C:4]2[CH:3]=1.[O:23]1[CH2:26][CH:25]([N:27]2[CH:31]=[C:30](B3OC(C)(C)C(C)(C)O3)[CH:29]=[N:28]2)[CH2:24]1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].C1(P(C2CCCCC2)C2C=CC=CC=2C2C(C(C)C)=CC(C(C)C)=CC=2C(C)C)CCCCC1>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>[CH:17]1([CH:13]([N:11]2[CH:12]=[C:8]([C:6]3[N:5]4[CH:20]=[CH:21][N:22]=[C:4]4[CH:3]=[C:2]([C:30]4[CH:29]=[N:28][N:27]([CH:25]5[CH2:26][O:23][CH2:24]5)[CH:31]=4)[N:7]=3)[CH:9]=[N:10]2)[CH2:14][C:15]#[N:16])[CH2:19][CH2:18]1

Participants

7

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 67455169HCID 67455169, compound2×HCID 866853033-(4-(7-chloroimidazo[1,2-c]pyrimidin-5-yl)-1H-pyrazol-1-yl)-3-cyclopropylpropanenitrile

Product 1

HCID 682308443-Cyclopropyl-3-(4-(7-(1-(oxetan-3-yl)-1H-pyrazol-4-yl)imidazo[1,2-c]pyrimidin-5-yl)-1H-pyrazol-1-yl)propanenitrileYield 50.6%

Reagents, catalysts & solvents 2

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

Conditions

Temperature
75 °C

Procedure

To a flask charged with 3-(4-(7-chloroimidazo[1,2-c]pyrimidin-5-yl)-1H-pyrazol-1-yl)-3-cyclopropylpropanenitrile (Preparation M; 0.050 g, 0.16 mmol), 1-(oxetan-3-yl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (Table 2, compound f; 0.078 g, 0.21 mmol), and potassium phosphate (0.24 mL, 0.48 mmol) was added 2 mL of dioxane and argon was bubbled through for 5 minutes before dicyclohexyl(2′,4′,6′-triisopropylbiphenyl-2-yl)phosphine (0.015 g, 0.032 mmol) and tris(dibenzylideneacetone)dipalladium (0.015 g, 0.016 mmol) were added. The reaction was fitted with a septum and argon was bubbled through for 10 minutes before it was sealed and then heated to 75° C. for 2 hours. The reaction mixture was diluted with dichloromethane and loaded directly onto a silica gel column pre-wetted and eluted with ethyl acetate containing 0.5% ammonium hydroxide to afford the title compound (0.034 g, 0.081 mmol, 50% yield). MS (apci) m/z=401.2 (M+H).

Workup

  1. additionwere added
  2. customThe reaction was fitted with a septum and argon
  3. customwas bubbled through for 10 minutes before it
  4. customwas sealed
  5. additionThe reaction mixture was diluted with dichloromethane
  6. washeluted with ethyl acetate containing 0.5% ammonium hydroxide

Sources & evidence

ORD record
ord-e8e0e9fd0eb94b9fa3a830a8f7a6ff57
Source dataset
uspto-grants-2015_02
Patent number
US08962596B2

Reaction notes

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