Triethylamine → (R)-tert-butyl 1-(5-bromo-3-(2-cyanoacetamido)-1H-pyrrolo[2,3-b]pyridin-4-yl)piperidin-3-ylcarbamate

HRID 408374Notes

Reaction equation

HRID 408374 reaction equation
[C:1]([CH2:3][C:4]([OH:6])=O)#[N:2].C1N(P(Cl)(N2C(=O)OCC2)=O)C(=O)OC1.C(N(CC)CC)C.[NH2:29][C:30]1[C:38]2[C:33](=[N:34][CH:35]=[C:36]([Br:53])[C:37]=2[N:39]2[CH2:44][CH2:43][CH2:42][C@@H:41]([NH:45][C:46](=[O:52])[O:47][C:48]([CH3:51])([CH3:50])[CH3:49])[CH2:40]2)[NH:32][CH:31]=1>CC#N.O.O.CN1C(=O)CCC1>[Br:53][C:36]1[C:37]([N:39]2[CH2:44][CH2:43][CH2:42][C@@H:41]([NH:45][C:46](=[O:52])[O:47][C:48]([CH3:50])([CH3:49])[CH3:51])[CH2:40]2)=[C:38]2[C:30]([NH:29][C:4](=[O:6])[CH2:3][C:1]#[N:2])=[CH:31][NH:32][C:33]2=[N:34][CH:35]=1

Participants

8

Reactant 4

HCID 8471TriethylamineHCID 9740Cyanoacetic acidHCID 152842Bis(2-oxo-3-oxazolidinyl)phosphinic chlorideHCID 67045407(R)-tert-butyl 1-(3-amino-5-bromo-1H-pyrrolo[2,3-b]pyridin-4-yl)piperidin-3-ylcarbamate

Product 1

HCID 67045531(R)-tert-butyl 1-(5-bromo-3-(2-cyanoacetamido)-1H-pyrrolo[2,3-b]pyridin-4-yl)piperidin-3-ylcarbamateYield 26%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 13387N-methyl-2-pyrrolidoneSolventHCID 18373917Acetonitrile--water (1/1)Solvent

Procedure

2-Cyanoacetic acid (0.332 g, 3.90 mmol), BOP-Cl (0.993 g, 3.90 mmol), and triethylamine (1.02 mL, 7.31 mmol) were added to an NMP solution (2 mL) of (R)-tert-butyl 1-(3-amino-5-bromo-1H-pyrrolo[2,3-b]pyridin-4-yl)piperidin-3-ylcarbamate (0.200 g, 0.487 mmol; Example 98, Step A). The reaction was then stirred for 18 hours, then poured into water, and extracted with DCM. The combined organic fractions were dried (MgSO4), filtered, and concentrated to give the crude product, which was purified by reverse phase chromatography (Biotage SP4, C-18 25M+, 5-95% CH3CN/water) to give (R)-tert-butyl 1-(5-bromo-3-(2-cyanoacetamido)-1H-pyrrolo[2,3-b]pyridin-4-yl)piperidin-3-ylcarbamate (0.06 g, 26% yield).

Workup

  1. extractionextracted with DCM
  2. dry with materialThe combined organic fractions were dried (MgSO4)
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customto give the crude product, which
  6. customwas purified by reverse phase chromatography (Biotage SP4

Sources & evidence

ORD record
ord-66e79942bcc14dd0af9bfc5174f22d58
Source dataset
uspto-grants-2014_06
Patent number
US08758830B2

Reaction notes

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