2-bromo-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine → (3S,5S)-3-methyl-5-{2-methylsulfany-l-5-[5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazin-2-yl]-pyrimidin-4-ylamino}-piperidine-1-carboxylic acid benzyl ester

HRID 1916155Notes

Reaction equation

HRID 1916155 reaction equation
Br[C:2]1[N:3]=[C:4]2[CH:10]=[CH:9][N:8]([CH2:11][O:12][CH2:13][CH2:14][Si:15]([CH3:18])([CH3:17])[CH3:16])[C:5]2=[N:6][CH:7]=1.C[Sn](C)(C)[Sn](C)(C)C.Br[C:28]1[C:29]([NH:36][C@H:37]2[CH2:42][C@H:41]([CH3:43])[CH2:40][N:39]([C:44]([O:46][CH2:47][C:48]3[CH:53]=[CH:52][CH:51]=[CH:50][CH:49]=3)=[O:45])[CH2:38]2)=[N:30][C:31]([S:34][CH3:35])=[N:32][CH:33]=1>[Pd].C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1(C)C=CC=CC=1>[CH2:47]([O:46][C:44]([N:39]1[CH2:38][C@@H:37]([NH:36][C:29]2[C:28]([C:2]3[N:3]=[C:4]4[CH:10]=[CH:9][N:8]([CH2:11][O:12][CH2:13][CH2:14][Si:15]([CH3:18])([CH3:17])[CH3:16])[C:5]4=[N:6][CH:7]=3)=[CH:33][N:32]=[C:31]([S:34][CH3:35])[N:30]=2)[CH2:42][C@H:41]([CH3:43])[CH2:40]1)=[O:45])[C:48]1[CH:53]=[CH:52][CH:51]=[CH:50][CH:49]=1

Participants

7

Reactant 3

HCID 575165972-bromo-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazineHCID 58177451(3S,5S)-benzyl 3-(5-bromo-2-(methylthio)pyrimidin-4-ylamino)-5-methylpiperidine-1-carboxylateHCID 178477788HCID 178477788, compound

Product 1

HCID 69811559(3S,5S)-3-methyl-5-{2-methylsulfany-l-5-[5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazin-2-yl]-pyrimidin-4-ylamino}-piperidine-1-carboxylic acid benzyl esterYield 35.5%

Reagents, catalysts & solvents 3

HCID 23938PalladiumCatalystHCID 178418397HCID 178418397, compoundCatalystHCID 1140TolueneSolvent

Procedure

A degassed toluene (15 ml) solution of 2-bromo-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine (1.0 g, 3.0 mmol), 1,1,1,2,2,2-hexamethyldistannane (1.0 g, 3.1 mmol), and tetrakis(triphenylphosphine)palladium(0) (176 mg, 0.15 mmol) was treated in a similar manner as Example 76, step 3. To this was added (3S,5S)-benzyl 3-(5-bromo-2-(methylthio)pyrimidin-4-ylamino)-5-methylpiperidine-1-carboxylate (1.37 g, 3.0 mmol) and another 176 mg of palladium catalyst and following Example 76, step 3. (3S,5S)-3-methyl-5-{2-methylsulfany-l-5-[5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazin-2-yl]-pyrimidin-4-ylamino}-piperidine-1-carboxylic acid benzyl ester (660 mg, 35%) could be isolated as an oil and taken to the next step. (0227-160)

Sources & evidence

ORD record
ord-58477f074d9e40fca1ebaced4e656cb3
Source dataset
uspto-grants-2013_12
Patent number
US08618103B2

Reaction notes

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