Water → HCID 67081456, compound

HRID 2203953Notes

Reaction equation

HRID 2203953 reaction equation
[NH2:1][C:2]1[C:10]2[C:5](=[N:6][CH:7]=[C:8]([Cl:26])[C:9]=2[N:11]2[CH2:16][CH2:15][CH2:14][C@@H:13]([N:17]([CH3:25])[C:18](=[O:24])[O:19][C:20]([CH3:23])([CH3:22])[CH3:21])[CH2:12]2)[NH:4][CH:3]=1.[C:27](Cl)(=[O:30])[CH2:28][CH3:29].[Li+].[OH-].O>CN1C(=O)CCC1.N1C=CC=CC=1.CC#N.O.C(Cl)Cl>[Cl:26][C:8]1[C:9]([N:11]2[CH2:16][CH2:15][CH2:14][C@@H:13]([N:17]([CH3:25])[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:27](=[O:30])[CH2:28][CH3:29])=[CH:3][NH:4][C:5]2=[N:6][CH:7]=1

Participants

9

Reactant 4

HCID 962WaterHCID 3939Lithium HydroxideHCID 62324Propionyl chlorideHCID 67081885HCID 67081885, compound

Product 1

HCID 67081456HCID 67081456, compoundYield 46.5%

Reagents, catalysts & solvents 4

HCID 1049PyridineSolventHCID 6344DichloromethaneSolventHCID 13387N-methyl-2-pyrrolidoneSolventHCID 18373917Acetonitrile--water (1/1)Solvent

Procedure

(R)-tert-Butyl 1-(3-amino-5-chloro-1H-pyrrolo[2,3-b]pyridin-4-yl)piperidin-3-yl(methyl)carbamate (0.300 g, 0.790 mmol; Example 112, Step A) in NMP (2 mL), pyridine (1 mL) and propionyl chloride (0.365 g, 3.95 mmol) were stirred at room temperature for 1 hour. 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 separated, dried, filtered, and concentrated. The crude residue was purified by reverse phase chromatography (Biotage SP4, C-18 25M+, 0-95% CH3CN/water) to give (R)-tert-butyl 1-(5-chloro-3-propionamido-1H-pyrrolo[2,3-b]pyridin-4-yl)piperidin-3-yl(methyl)carbamate (0.160 g, 46% yield).

Workup

  1. customthe organic fraction was separated
  2. customdried
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customThe crude residue was purified by reverse phase chromatography (Biotage SP4

Sources & evidence

ORD record
ord-2b6c70f6978f4a3aaff58f9e401ff2e6
Source dataset
uspto-grants-2016_06
Patent number
US09365568B2

Reaction notes

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