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

HRID 875867Notes

Reaction equation

HRID 875867 reaction equation
[NH2:1][C:2]1[C:10]2[C:5](=[N:6][CH:7]=[C:8]([Cl:25])[C:9]=2[N:11]2[CH2:16][CH2:15][CH2:14][C@@H:13]([NH:17][C:18](=[O:24])[O:19][C:20]([CH3:23])([CH3:22])[CH3:21])[CH2:12]2)[NH:4][CH:3]=1.[C:26](Cl)(=[O:29])[CH2:27][CH3:28].[Li+].[OH-]>CN1C(=O)CCC1.C(Cl)Cl.O.N1C=CC=CC=1>[Cl:25][C:8]1[C:9]([N:11]2[CH2:16][CH2:15][CH2:14][C@@H:13]([NH:17][C:18](=[O:24])[O:19][C:20]([CH3:21])([CH3:22])[CH3:23])[CH2:12]2)=[C:10]2[C:2]([NH:1][C:26](=[O:29])[CH2:27][CH3:28])=[CH:3][NH:4][C:5]2=[N:6][CH:7]=1

Participants

8

Reactant 3

HCID 3939Lithium HydroxideHCID 62324Propionyl chlorideHCID 67045610(R)-tert-butyl 1-(3-amino-5-chloro-1H-pyrrolo[2,3-b]pyridin-4-yl)piperidin-3-ylcarbamate

Product 1

HCID 67045346(R)-tert-butyl 1-(5-chloro-3-propionamido-1H-pyrrolo[2,3-b]pyridin-4-yl)piperidin-3-ylcarbamateYield 63.6%

Reagents, catalysts & solvents 4

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

Procedure

DCM (2 mL) and pyridine (1 mL) were added to (R)-tert-butyl 1-(3-amino-5-chloro-1H-pyrrolo[2,3-b]pyridin-4-yl)piperidin-3-ylcarbamate (0.3 g, 0.820 mmol; Example 91, Step A) in NMP (2 mL), and then propionyl chloride (0.228 g, 2.46 mmol) was added. The reaction was then stirred for 1 hour at room temperature, and then 3M aqueous LiOH (3 mL) was added. 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. Purification of the crude product by reverse phase HPLC (5-95% ACN in water) gave the product (R)-tert-butyl 1-(5-chloro-3-propionamido-1H-pyrrolo[2,3-b]pyridin-4-yl)piperidin-3-ylcarbamate (0.220 g, 63.6% yield).

Workup

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

Sources & evidence

ORD record
ord-15b06962d24c4cae960cb1b7d9eb804a
Source dataset
uspto-grants-2015_03
Patent number
US08981085B2

Reaction notes

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