Triethylamine → HCID 70035087, compound

HRID 431832Notes

Reaction equation

HRID 431832 reaction equation
Br[C:2]1[CH:3]=[N:4][C:5]([N:8]2[CH2:12][C@H:11]([S:13][C:14]([C:27]3[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=3)([C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=3)[C:15]3[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=3)[CH2:10][C@H:9]2[CH2:33][O:34][CH2:35][C:36]2[CH:41]=[C:40]([F:42])[C:39]([F:43])=[CH:38][C:37]=2[F:44])=[N:6][CH:7]=1.[C:45]([Si:47]([CH3:50])([CH3:49])[CH3:48])#[CH:46].CCN(CC)CC>CN(C=O)C.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.Cl[Pd]Cl.[Cu]I>[F:44][C:37]1[CH:38]=[C:39]([F:43])[C:40]([F:42])=[CH:41][C:36]=1[CH2:35][O:34][CH2:33][C@@H:9]1[CH2:10][C@@H:11]([S:13][C:14]([C:21]2[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=2)([C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)[C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)[CH2:12][N:8]1[C:5]1[N:6]=[CH:7][C:2]([C:46]#[C:45][Si:47]([CH3:50])([CH3:49])[CH3:48])=[CH:3][N:4]=1

Participants

7

Reactant 3

HCID 8471TriethylamineHCID 66111TrimethylsilylacetyleneHCID 70003684HCID 70003684, compound

Product 1

HCID 70035087HCID 70035087, compoundYield 9.1%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 6102075Dichlorobis(triphenylphosphine)palladiumCatalystHCID 6228DimethylformamideSolvent2×

Procedure

A solution of 0.68 g (1 mmol) (2S,4R)-5-Bromo-2-[2-(2,4,5-trifluoro-benzyloxymethyl)-4-tritylsulfanyl-pyrrolidin-1-yl]-pyrimidine, 15 mg (0.022 mmol) of bis(triphenylphosphine)palladium(II)dichloride and 9.5 mg copper(I)iodide in 0.4 ml DMF was treated at 80° C. for 1 h with a solution of 0.35 ml (2.5 mmol) ethinyltrimethylsilane and 1.87 ml Et3N in 1.5 ml DMF. The same solution was added again during 1 h and after 4 h extracted with pentane (3×)/H2O (2×). The organic phase was dried (Na2SO4), evaporated and purified by flash-chromatography on silica gel (toluene) to give 0.063 g (9%) (2S,4R)-2-[2-(2,4,5-Trifluoro-benzyloxymethyl)-4-tritylsulfanyl-pyrrolidin-1-yl]-5-trimethylsilanylethynyl-pyrimidine, MS: 694 (MH+). TFA/triisopropylsilane deprotection (see General method for S-deprotection, Method D) gave (3R,5S)-5-(2,4,5-Trifluoro-benzyloxymethyl)-1-(5-trimethylsilanylethynyl-pyrimidin-2-yl)-pyrrolidine-3-thiol, MS: 452 (MH+).

Workup

  1. additionThe same solution was added again during 1 h and after 4 h
  2. extractionextracted with pentane (3×)/H2O (2×)
  3. dry with materialThe organic phase was dried (Na2SO4)
  4. customevaporated
  5. custompurified by flash-chromatography on silica gel (toluene)

Sources & evidence

ORD record
ord-7cc1c1794f4d4f9fba972d37a4835ca0
Source dataset
uspto-grants-2003_12
Patent number
US06660738B2

Reaction notes

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