Water → HCID 67457655, compound

HRID 1853010Notes

Reaction equation

HRID 1853010 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:13]=[C:12]([C:14]3[CH:15]=[N:16][N:17]([CH2:19][O:20][CH2:21][CH2:22][Si:23]([CH3:26])([CH3:25])[CH3:24])[CH:18]=3)[N:11]3[CH:27]=[CH:28][N:29]=[C:10]3[CH:9]=2)=[CH:4][CH:3]=1.[CH3:30][N:31]1[CH:35]=[C:34](B2OC(C)(C)C(C)(C)O2)[CH:33]=[N:32]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.O>C(Cl)Cl.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].C(O)(C)C>[CH3:30][N:31]1[CH:35]=[C:34]([C:2]2[CH:3]=[CH:4][C:5]([C:8]3[N:13]=[C:12]([C:14]4[CH:15]=[N:16][N:17]([CH2:19][O:20][CH2:21][CH2:22][Si:23]([CH3:25])([CH3:24])[CH3:26])[CH:18]=4)[N:11]4[CH:27]=[CH:28][N:29]=[C:10]4[CH:9]=3)=[CH:6][CH:7]=2)[CH:33]=[N:32]1

Participants

9

Reactant 5

HCID 962WaterHCID 62657Potassium Phosphate, TribasicHCID 27739871-Methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazoleHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 67457604HCID 67457604, compound

Product 1

HCID 67457655HCID 67457655, compoundYield 85.9%

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 3776IsopropanolSolventHCID 6344DichloromethaneSolvent

Procedure

A flask charged with 7-(4-bromophenyl)-5-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazol-4-yl)imidazo[1,2-c]pyrimidine (Preparation L; 0.200 g, 0.425 mmol), 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (0.195 g, 0.935 mmol), potassium phosphate (0.271 g, 1.28 mmol), dicyclohexyl(2′,4′,6′-triisopropylbiphenyl-2-yl)phosphine (0.0507 g, 0.106 mmol), and tris(dibenzylideneacetone)dipalladium (0.0389 g, 0.0425 mmol) was evacuated and backfilled with argon. To the reaction was added 4 mL of isopropanol (degassed with argon for 30 minutes) and water (0.0460 mL, 2.55 mmol). The reaction was sealed and allowed to proceed at 100° C. for 4 hours. The reaction was then diluted with DCM (100 mL), dried over MgSO4, filtered, and concentrated under reduced pressure. The resulting crude was then purified by means of silica gel chromatography eluting with a linear gradient of 1-5% methanol in DCM to afford 7-(4-(1-methyl-1H-pyrazol-4-yl)phenyl)-5-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazol-4-yl)imidazo[1,2-c]pyrimidine (0.174 g, 0.365 mmol, 85.9% yield). MS (apci) m/z=472.2 (M+H).

Workup

  1. customwas evacuated
  2. customThe reaction was sealed
  3. dry with materialdried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customThe resulting crude was then purified by means of silica gel chromatography
  7. washeluting with a linear gradient of 1-5% methanol in DCM

Sources & evidence

ORD record
ord-cbea79340de84d83bf78ea611fb5eaec
Source dataset
uspto-grants-2015_02
Patent number
US08962596B2

Reaction notes

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