Trimethylsilylacetylene → N,N-di(1,1-dimethylethoxycarbonyl)-3-(1-(2,3-difluorophenyl)-1H-tetrazol-5-yl)-5-(2-(trimethylsilyl)ethynyl)pyridin-2-amine

HRID 254013Notes

Reaction equation

HRID 254013 reaction equation
[CH3:1][C:2]([CH3:35])([O:4][C:5]([N:7]([C:28]([O:30][C:31]([CH3:34])([CH3:33])[CH3:32])=[O:29])[C:8]1[C:13]([C:14]2[N:18]([C:19]3[CH:24]=[CH:23][CH:22]=[C:21]([F:25])[C:20]=3[F:26])[N:17]=[N:16][N:15]=2)=[CH:12][C:11](Br)=[CH:10][N:9]=1)=[O:6])[CH3:3].[C:36]([Si:38]([CH3:41])([CH3:40])[CH3:39])#[CH:37]>C(NCC)C.C(Cl)Cl.[Cu]I>[CH3:1][C:2]([CH3:35])([O:4][C:5]([N:7]([C:28]([O:30][C:31]([CH3:34])([CH3:33])[CH3:32])=[O:29])[C:8]1[C:13]([C:14]2[N:18]([C:19]3[CH:24]=[CH:23][CH:22]=[C:21]([F:25])[C:20]=3[F:26])[N:17]=[N:16][N:15]=2)=[CH:12][C:11]([C:37]#[C:36][Si:38]([CH3:41])([CH3:40])[CH3:39])=[CH:10][N:9]=1)=[O:6])[CH3:3]

Participants

6

Reactant 2

HCID 66111TrimethylsilylacetyleneHCID 58179849N,N-di(1,1-dimethylethoxycarbonyl)-3-(1-(2,3-difluorophenyl)-1H-tetrazol-5-yl)-5-bromopyridin-2-amine

Product 1

HCID 58179633N,N-di(1,1-dimethylethoxycarbonyl)-3-(1-(2,3-difluorophenyl)-1H-tetrazol-5-yl)-5-(2-(trimethylsilyl)ethynyl)pyridin-2-amineYield 30%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 6344DichloromethaneSolvent2×HCID 8021DiethylamineSolvent

Conditions

Temperature
50 °C

Procedure

In a tube was placed N,N-di(1,1-dimethylethoxycarbonyl)-3-(1-(2,3-difluorophenyl)-1H-tetrazol-5-yl)-5-bromopyridin-2-amine (2.3 g, 4.1 mmol) in diethylamine (10 mL) with ethynyltrimethylsilane (1.5 g, 15.3 mmol) and the reaction was deoxygenated with a stream of nitrogen gas. To the mixture was added copper(I) iodide (554 mg, 2.9 mmol). The reaction vessel was sealed and warmed to 50° C. to achieve dissolution. To the mixture was added PdCl2dppf2.CH2Cl2 (190 mg, 0.06 eq). The reaction vessel was sealed and the mixture sonicated at 50° C. for 10 minutes. The reaction was diluted with methylene chloride, filtered through Celite™, concentrated, and purified by silica gel chromatography (10% ethyl acetate/hexane to 50% ethyl acetate/hexane) to give N,N-di(1,1-dimethylethoxycarbonyl)-3-(1-(2,3-difluorophenyl)-1H-tetrazol-5-yl)-5-(2-(trimethylsilyl)ethynyl)pyridin-2-amine (713 mg, 1.2 mmol, 30%) as a yellow solid; LC-MS: m/e=471.3 [M-Boc+H].

Workup

  1. customIn a tube was placed
  2. customThe reaction vessel was sealed
  3. dissolutiondissolution
  4. additionTo the mixture was added PdCl2dppf2
  5. customThe reaction vessel was sealed
  6. customthe mixture sonicated at 50° C. for 10 minutes
  7. filtrationfiltered through Celite™
  8. concentrationconcentrated
  9. custompurified by silica gel chromatography (10% ethyl acetate/hexane to 50% ethyl acetate/hexane)

Sources & evidence

ORD record
ord-9dc90a08d5a644babe1f27529013115e
Source dataset
uspto-grants-2011_01
Patent number
US07872031B2

Reaction notes

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