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

HRID 1034845Notes

Reaction equation

HRID 1034845 reaction equation
[C:1](Cl)(=[O:5])[CH2:2][CH2:3][CH3:4].[NH2:7][C:8]1[C:16]2[C:11](=[N:12][CH:13]=[C:14]([Br:31])[C:15]=2[N:17]2[CH2:22][CH2:21][CH2:20][C@@H:19]([NH:23][C:24](=[O:30])[O:25][C:26]([CH3:29])([CH3:28])[CH3:27])[CH2:18]2)[NH:10][CH:9]=1.C(N(CC)CC)C.[Li+].[OH-]>ClCCl.CN1C(=O)CCC1.C1COCC1.CC#N.O>[Br:31][C:14]1[C:15]([N:17]2[CH2:22][CH2:21][CH2:20][C@@H:19]([NH:23][C:24](=[O:30])[O:25][C:26]([CH3:28])([CH3:27])[CH3:29])[CH2:18]2)=[C:16]2[C:8]([NH:7][C:1](=[O:5])[CH2:2][CH2:3][CH3:4])=[CH:9][NH:10][C:11]2=[N:12][CH:13]=1

Participants

9

Reactant 4

HCID 3939Lithium HydroxideHCID 8471TriethylamineHCID 8855Butyryl chlorideHCID 67045407(R)-tert-butyl 1-(3-amino-5-bromo-1H-pyrrolo[2,3-b]pyridin-4-yl)piperidin-3-ylcarbamate

Product 1

HCID 67045202(R)-tert-butyl 1-(5-bromo-3-butyramido-1H-pyrrolo[2,3-b]pyridin-4-yl)piperidin-3-ylcarbamateYield 100.1%

Reagents, catalysts & solvents 4

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolventHCID 13387N-methyl-2-pyrrolidoneSolventHCID 18373917Acetonitrile--water (1/1)Solvent

Procedure

Butyryl chloride (234 mg, 2.19 mmol) in anhydrous dichloromethane (0.5 mL) was added dropwise to a solution of (R)-tert-butyl 1-(3-amino-5-bromo-1H-pyrrolo[2,3-b]pyridin-4-yl)piperidin-3-ylcarbamate (150 mg, 0.366 mmol) and triethylamine (259 mg, 0.357 mL, 2.56 mmol) in NMP (0.900 mL) cooled on an ice-bath. The mixture was stirred at ambient temperature for 1 hour. The mixture was diluted with THF (10 mL), treated with an aqueous 2N LiOH solution (3 mL) and stirred for 1 hour. The THF was evaporated. The residue was stirred with water (20 mL) and extracted with EtOAc (3×20 mL). The combined organic extracts were dried over MgSO4, filtered and concentrated. The residue was purified by reverse phase chromatography (Biotage SP4, C-18 25M+, 15-80% CH3CN/water, 25CV) to give (R)-tert-butyl 1-(5-bromo-3-butyramido-1H-pyrrolo[2,3-b]pyridin-4-yl)piperidin-3-ylcarbamate (176 mg, 100% yield) as a solid. LCMS (APCI+) m/z 482.1, 382, 380 (M+H)+, Retention time=3.80 minutes.

Workup

  1. temperaturecooled on an ice-bath
  2. stirringstirred for 1 hour
  3. customThe THF was evaporated
  4. stirringThe residue was stirred with water (20 mL)
  5. extractionextracted with EtOAc (3×20 mL)
  6. dry with materialThe combined organic extracts were dried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe residue was purified by reverse phase chromatography (Biotage SP4

Sources & evidence

ORD record
ord-8e0142037a714a2598feaf81ef9d92bb
Source dataset
uspto-grants-2013_10
Patent number
US08545897B2

Reaction notes

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