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Diisopropylamine → 3-Pyrimidin-5-ylethynyl-7-trifluoromethyl-5-(4-trifluoromethyl-phenyl)-pyrazolo[1,5-a]pyrimidine

HRID 1293793
Notes
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Reaction equation

HRID 1293793 reaction equation
[C:1]([C:3]1[CH:4]=[N:5][N:6]2[C:11]([C:12]([F:15])([F:14])[F:13])=[CH:10][C:9]([C:16]3[CH:21]=[CH:20][C:19]([C:22]([F:25])([F:24])[F:23])=[CH:18][CH:17]=3)=[N:8][C:7]=12)#[CH:2].Br[C:27]1[CH:32]=[CH:31][N:30]=[CH:29][N:28]=1.C(P(C(C)(C)C)C(C)(C)C)(C)(C)C.C(NC(C)C)(C)C>O1CCOCC1.[Cu]I.CCOC(C)=O.CCCCCCC>[N:28]1[CH:27]=[C:32]([C:2]#[C:1][C:3]2[CH:4]=[N:5][N:6]3[C:11]([C:12]([F:14])([F:13])[F:15])=[CH:10][C:9]([C:16]4[CH:21]=[CH:20][C:19]([C:22]([F:25])([F:24])[F:23])=[CH:18][CH:17]=4)=[N:8][C:7]=23)[CH:31]=[N:30][CH:29]=1
ParticipantsConditionsProcedureWorkupSources & evidenceReaction notes

Participants

8

Reactant 4

HCID 7912DiisopropylamineHCID 83681Tris(1,1-dimethylethyl)phosphineHCID 127522204-BromopyrimidineHCID 715397323-Ethynyl-7-trifluoromethyl-5-(4-trifluoromethyl-phenyl)-pyrazolo[1,5-a]pyrimidine

Product 1

HCID 866080383-Pyrimidin-5-ylethynyl-7-trifluoromethyl-5-(4-trifluoromethyl-phenyl)-pyrazolo[1,5-a]pyrimidineYield 68%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 312751,4-DioxaneSolvent2×HCID 21899848Ethylacetate heptaneSolvent

Conditions

Temperature
23 °C

Procedure

To a flask was added 3-ethynyl-7-trifluoromethyl-5-(4-trifluoromethyl-phenyl)-pyrazolo[1,5-a]pyrimidine (example C.1) (159 mg, 0.45 mmol), 4-Bromopyrimidine (87 mg, 0.55 mmol, commercially available [CAS 4595-59-9]), PdCl2(NCPh)2 (13 mg, 7 mol %), and CuI (10 mg, 12 mol %). The flask was charged with Ar, then 3 mL of dioxane (degassed with Ar), tri-(tert-butyl)phosphine (0.12 mL of a 0.25M soln in dioxane, 33 mol %), and diisopropylamine (0.15 mL) were added. The r×n mixture was stirred at 23° C. under Ar overnight, then filtered through a pad of Si-gel, concentrated, purified by Si-gel chromatography (EtOAc/heptane 5-40:95–60) to give an orange solid. Recrytallization from EtOAc/heptane (1:2) yielded the product as an orange solid (131 mg, 68%). MS (ISP) 434.1 [(M+H)+]; mp 175° C.

Workup

  1. additionThe flask was charged with Ar
  2. filtrationfiltered through a pad of Si-gel
  3. concentrationconcentrated
  4. custompurified by Si-gel chromatography (EtOAc/heptane 5-40:95–60)
  5. customto give an orange solid

Sources & evidence

ORD record
ord-8824ce10b4a7409fa7a8a34816373bf6
Source dataset
uspto-grants-2007_07
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US07238808B2

Reaction notes

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On this pageParticipantsConditionsProcedureWorkupSources & evidenceReaction notes