Triethylamine → HCID 69967398, compound

HRID 842022Notes

Reaction equation

HRID 842022 reaction equation
[C:1]([O:5][C:6]([N:8]([CH:36]1[CH2:41][CH2:40][O:39][CH2:38][CH2:37]1)[CH2:9][CH2:10][NH:11][C:12]1[N:17]2[N:18]=[C:19]([CH3:34])[C:20]([C:21]3[C:26]([Cl:27])=[CH:25][C:24](OS(C)(=O)=O)=[CH:23][C:22]=3[Cl:33])=[C:16]2[N:15]=[C:14]([CH3:35])[CH:13]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C(N(CC)CC)C.[CH3:49][Si:50]([C:53]#[CH:54])([CH3:52])[CH3:51]>C(#N)C.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>[C:1]([O:5][C:6](=[O:7])[N:8]([CH2:9][CH2:10][NH:11][C:12]1[N:17]2[N:18]=[C:19]([CH3:34])[C:20]([C:21]3[C:22]([Cl:33])=[CH:23][C:24]([C:54]#[C:53][Si:50]([CH3:52])([CH3:51])[CH3:49])=[CH:25][C:26]=3[Cl:27])=[C:16]2[N:15]=[C:14]([CH3:35])[CH:13]=1)[CH:36]1[CH2:37][CH2:38][O:39][CH2:40][CH2:41]1)([CH3:4])([CH3:2])[CH3:3]

Participants

7

Reactant 3

HCID 8471TriethylamineHCID 66111TrimethylsilylacetyleneHCID 88078764HCID 88078764, compound

Product 1

HCID 69967398HCID 69967398, compoundYield 89%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418476HCID 178418476, compoundCatalystHCID 6342AcetonitrileSolvent

Conditions

Temperature
65 °C

Procedure

A suspension of methanesulfonic acid 4-(7-{2-[tert-butoxycarbonyl-(tetrahydro-pyran-4-yl)-amino]-ethylamino}-2,5-dimethyl-pyrazolo[1,5-a]pyrimidin-3-yl)-3,5-dichloro-phenyl ester (1.5 g, 2.2 mmol) in acetonitrile (5 mL)/triethylamine (1.9 mL) was degassed (3×) by alternately pulling a vacuum followed by repressurization with nitrogen. Trimethylsilylacetylene (0.50 mL, 3.6 mmol), dichlorobis(triphenylphosphine)palladium (65 mg, 0.093 mmol), and copper(I) iodide (42 mg, 0.22 mmol) were added, and the mixture was degassed (3×) again. The mixture was stirred for 4 hours at 65° C., the black mixture was extracted from saturated aqueous sodium bicarbonate with methylene chloride, dried (Na2SO4), filtered through Celite, concentrated under reduced pressure, and then chromatographed (7:3 hexanes/ethyl acetate) to give the product as a light brown foam (1.2 g, 89%): +APcI MS (M+1)+630; 1H NMR (CDCl3) δ: 7.51 (s, 2H), 5.82 (s, 1H), 2.44 (s, 3H), 2.23 (s, 3H), 1.53 (s, 9H), 0.24 (s, 9H).

Workup

  1. customwas degassed (3×)
  2. customthe mixture was degassed (3×) again
  3. extractionthe black mixture was extracted from saturated aqueous sodium bicarbonate with methylene chloride
  4. dry with materialdried (Na2SO4)
  5. filtrationfiltered through Celite
  6. concentrationconcentrated under reduced pressure
  7. customchromatographed (7:3 hexanes/ethyl acetate)

Sources & evidence

ORD record
ord-8d751c67f1c544cbbba5d0b0e82c5a35
Source dataset
uspto-grants-2002_04
Patent number
US06372743B1

Reaction notes

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