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

HRID 408378Notes

Reaction equation

HRID 408378 reaction equation
[C:1](Cl)(=[O:4])[CH2:2][CH3:3].[NH2:6][C:7]1[C:15]2[C:10](=[N:11][CH:12]=[C:13]([Br:30])[C:14]=2[N:16]2[CH2:21][CH2:20][CH2:19][C@@H:18]([NH:22][C:23](=[O:29])[O:24][C:25]([CH3:28])([CH3:27])[CH3:26])[CH2:17]2)[NH:9][CH:8]=1.[Li+].[OH-]>CN1C(=O)CCC1.C(Cl)Cl.O.N1C=CC=CC=1>[Br:30][C:13]1[C:14]([N:16]2[CH2:21][CH2:20][CH2:19][C@@H:18]([NH:22][C:23](=[O:29])[O:24][C:25]([CH3:27])([CH3:26])[CH3:28])[CH2:17]2)=[C:15]2[C:7]([NH:6][C:1](=[O:4])[CH2:2][CH3:3])=[CH:8][NH:9][C:10]2=[N:11][CH:12]=1

Participants

8

Reactant 3

HCID 3939Lithium HydroxideHCID 62324Propionyl chlorideHCID 67045407(R)-tert-butyl 1-(3-amino-5-bromo-1H-pyrrolo[2,3-b]pyridin-4-yl)piperidin-3-ylcarbamate

Product 1

HCID 67045151(R)-tert-butyl 1-(5-bromo-3-propionamido-1H-pyrrolo[2,3-b]pyridin-4-yl)piperidin-3-ylcarbamateYield 52.8%

Reagents, catalysts & solvents 4

HCID 962WaterSolventHCID 1049PyridineSolventHCID 6344DichloromethaneSolvent2×HCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

DCM (2 mL), pyridine (0.5 mL) and propionyl chloride (0.180 g, 1.95 mmol) were added to (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) in NMP (3 mL). The reaction was then stirred for 1 hour at room temperature. 3M aqueous LiOH (3 mL) was then added, and the reaction was stirred for 10 minutes. Water (10 mL) and DCM (10 mL) were then added, and the organic fraction was dried, filtered and concentrated to give the crude product. Purification by reverse phase HPLC (5-95% ACN in water) gave the product (R)-tert-butyl 1-(5-bromo-3-propionamido-1H-pyrrolo[2,3-b]pyridin-4-yl)piperidin-3-ylcarbamate (0.120 g, 52.8% yield).

Workup

  1. stirringthe reaction was stirred for 10 minutes
  2. customthe organic fraction was dried
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customto give the crude product
  6. customPurification by reverse phase HPLC (5-95% ACN in water)

Sources & evidence

ORD record
ord-d1c4df2edb934867a4ef660d82cd66f7
Source dataset
uspto-grants-2014_06
Patent number
US08758830B2

Reaction notes

Loading…