Tin atom → ((S)-1-methanesulfonyl-piperidin-3-yl)-{2-methylsulfanyl-5-[5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazin-2-yl]-pyrimidin-4-yl}-amine

HRID 1916117Notes

Reaction equation

HRID 1916117 reaction equation
N1C=CN=C2NC=CC=12.C[Sn](C)(C)[Sn](C)(C)C.[Sn].[CH3:19][Si:20]([CH3:39])([CH3:38])[CH2:21][CH2:22][O:23][CH2:24][N:25]1[C:29]2=[N:30][CH:31]=[C:32]([Sn](C)(C)C)[N:33]=[C:28]2[CH:27]=[CH:26]1.Br[C:41]1[C:42]([NH:49][C@H:50]2[CH2:55][CH2:54][CH2:53][N:52]([S:56]([CH3:59])(=[O:58])=[O:57])[CH2:51]2)=[N:43][C:44]([S:47][CH3:48])=[N:45][CH:46]=1>C1(C)C=CC=CC=1>[CH3:59][S:56]([N:52]1[CH2:53][CH2:54][CH2:55][C@H:50]([NH:49][C:42]2[C:41]([C:32]3[N:33]=[C:28]4[CH:27]=[CH:26][N:25]([CH2:24][O:23][CH2:22][CH2:21][Si:20]([CH3:39])([CH3:38])[CH3:19])[C:29]4=[N:30][CH:31]=3)=[CH:46][N:45]=[C:44]([S:47][CH3:48])[N:43]=2)[CH2:51]1)(=[O:58])=[O:57]

Participants

7

Reactant 5

HCID 5352426Tin atomHCID 53708035H-Pyrrolo[2,3-b]pyrazineHCID 581774595-(2-trimethylsilanyl-ethoxymethyl)-2-trimethylstannanyl-5H-pyrrolo[2,3-b]pyrazineHCID 69811702(5-bromo-2-methylsulfanyl-pyrimidin-4-yl)-((S)-1-methanesulfonyl-piperidin-3-yl)-amineHCID 178477788HCID 178477788, compound

Product 1

HCID 69812827((S)-1-methanesulfonyl-piperidin-3-yl)-{2-methylsulfanyl-5-[5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazin-2-yl]-pyrimidin-4-yl}-amine

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
97.5 °C

Procedure

A degassed toluene solution of 2-bromo-5-(2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine (200 mg, 0.61 mmol) and 1,1,1,2,2,2-hexamethyldistannane (220 mg, 0.67 mmol) was treated with tetrakistriphenylphosphine palladium (0) (35 mg, 0.03 mmol) and heated to 95-100° C. for 2 hours. When LCMS indicated conversion to the tin product, 5-(2-trimethylsilanyl-ethoxymethyl)-2-trimethylstannanyl-5H-pyrrolo[2,3-b]pyrazine, (MS (ES+): 412), the reaction was treated with (5-bromo-2-methylsulfanyl-pyrimidin-4-yl)-((S)-1-methanesulfonyl-piperidin-3-yl)-amine (80 mg, 0.21 mmol) and additional tetrakistriphenylphosphine palladium (0) (35 mg, 0.03 mmol) and heated to 100° C. for 16 hours. The reaction was cooled, filtered through celite, evaporated and purified by flash chromatography (60% ethyl acetate/hexane+2% triethylamine) to give 60 mg of ((S)-1-methanesulfonyl-piperidin-3-yl)-{2-methylsulfanyl-5-[5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazin-2-yl]-pyrimidin-4-yl}-amine. MS (ES+): 550.

Workup

  1. temperatureheated to 100° C. for 16 hours
  2. temperatureThe reaction was cooled
  3. filtrationfiltered through celite
  4. customevaporated
  5. custompurified by flash chromatography (60% ethyl acetate/hexane+2% triethylamine)

Sources & evidence

ORD record
ord-ccc92b329ecf414a8b01a4fd5e2808a3
Source dataset
uspto-grants-2013_12
Patent number
US08618103B2

Reaction notes

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