Triethylamine → HCID 67000372, compound

HRID 1293748Notes

Reaction equation

HRID 1293748 reaction equation
[F:1][CH:2]([F:23])[C:3]1[N:8]2[CH:9]=[N:10][C:11](I)=[C:7]2[N:6]=[C:5]([C:13]2[CH:18]=[CH:17][C:16]([C:19]([F:22])([F:21])[F:20])=[CH:15][CH:14]=2)[CH:4]=1.[CH3:24][Si:25]([C:28]#[CH:29])([CH3:27])[CH3:26].C(N(CC)CC)C>CN(C)C=O.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.[Cu]I.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[F:1][CH:2]([F:23])[C:3]1[N:8]2[CH:9]=[N:10][C:11]([C:29]#[C:28][Si:25]([CH3:27])([CH3:26])[CH3:24])=[C:7]2[N:6]=[C:5]([C:13]2[CH:18]=[CH:17][C:16]([C:19]([F:22])([F:21])[F:20])=[CH:15][CH:14]=2)[CH:4]=1

Participants

8

Reactant 3

HCID 8471TriethylamineHCID 66111TrimethylsilylacetyleneHCID 67001381HCID 67001381, compound

Product 1

HCID 67000372HCID 67000372, compoundYield 69.2%

Reagents, catalysts & solvents 4

HCID 11776TriphenylphosphineCatalystHCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418476HCID 178418476, compoundCatalystHCID 6228DimethylformamideSolvent

Procedure

A mixture of 4-difluoromethyl-8-iodo-2-(4-trifluoromethyl-phenyl)-imidazo[1,5-a]pyrimidine (2.45 g, 5.58 mmol), trimethylsilylacetylene (1.24 ml, 8.94 mmol) and triethylamine (2.08 ml, 14.9 mmol) in N,N-dimethylformamide (10 ml) was stirred for 10 min at room temperature while being purged with Argon, then PdCl2(PPh3)2 (105 mg, 0.15 mmol), PPh3 (78 mg, 0.3 mmol) and CuI (9 mg, 0.05 mmol) were added. Stirring was continued at 90° C. for 5 h. The reaction mixture was cooled to room temperature, diluted with ice-water (50 mL) and extracted with ethyl acetate (3×70 ml). The combined organic layers were washed with water (40 ml) and brine (40 ml), dried (MgSO4) and evaporated to give 4-difluoromethyl-2-(4-trifluoromethyl-phenyl)-8-trimethylsilanylethynyl-imidazo[1,5-a]pyrimidine (1.58 g, 69%) as a brown solid, which was dissolved in THF (15 ml) and MeOH (15 ml), while stirring at 0° C. potassium carbonate (51 mg, 0.37 mmol) was added and the mixture was stirred at 0° C. for 5 h. The mixture was diluted with ice water (50 ml) and extracted with TBME (2×80 ml). The combined organic layers were washed with brine (50 ml), dried (MgSO4) and evaporated. The crude product was further purified by flash chromatography on silica gel (heptane/EtOAc) followed by crystallization from diethyl ether/hexane to give 4-difluoromethyl-8-ethynyl-2-(4-trifluoromethyl-phenyl)-imidazo[1,5-a]pyrimidine (0.61 g, 49%) as a brown solid. MS (EI) 337.1 [(M)+]; mp 135° C.

Workup

  1. customwhile being purged with Argon
  2. stirringStirring
  3. waitwas continued at 90° C. for 5 h
  4. temperatureThe reaction mixture was cooled to room temperature
  5. extractionextracted with ethyl acetate (3×70 ml)
  6. washThe combined organic layers were washed with water (40 ml) and brine (40 ml)
  7. dry with materialdried (MgSO4)
  8. customevaporated

Sources & evidence

ORD record
ord-2e190edeed434459b1b51701f100d480
Source dataset
uspto-grants-2007_07
Patent number
US07238808B2

Reaction notes

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