Pyridine → HCID 71257392, compound

HRID 875874Notes

Reaction equation

HRID 875874 reaction equation
N1C=CC=CC=1.[C:7](Cl)(=[O:11])[CH:8]([CH3:10])[CH3:9].[NH2:13][C:14]1[C:22]2[C:17](=[N:18][CH:19]=[C:20]([Cl:38])[C:21]=2[N:23]2[CH2:28][CH2:27][CH2:26][C@@H:25]([N:29]([CH3:37])[C:30](=[O:36])[O:31][C:32]([CH3:35])([CH3:34])[CH3:33])[CH2:24]2)[NH:16][CH:15]=1.[Li+].[OH-]>CN1C(=O)CCC1.CC#N.O.C(Cl)Cl.O>[Cl:38][C:20]1[C:21]([N:23]2[CH2:28][CH2:27][CH2:26][C@@H:25]([N:29]([CH3:37])[C:30](=[O:36])[O:31][C:32]([CH3:33])([CH3:34])[CH3:35])[CH2:24]2)=[C:22]2[C:14]([NH:13][C:7](=[O:11])[CH:8]([CH3:10])[CH3:9])=[CH:15][NH:16][C:17]2=[N:18][CH:19]=1

Participants

9

Reactant 4

HCID 1049PyridineHCID 3939Lithium HydroxideHCID 62325Isobutyryl chlorideHCID 67081885HCID 67081885, compound

Product 1

HCID 71257392HCID 71257392, compoundYield 51%

Reagents, catalysts & solvents 4

HCID 962WaterSolventHCID 6344DichloromethaneSolventHCID 13387N-methyl-2-pyrrolidoneSolventHCID 18373917Acetonitrile--water (1/1)Solvent

Procedure

Pyridine (1 mL) and isobutyryl chloride (0.421 g, 3.95 mmol) were added to (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), and the reaction was 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 layer was separated, dried, filtered and concentrated. The crude residue was purified by reverse phase chromatography (Biotage SP4, C-18 12M+, 5-95% CH3CN/water) to give (R)-tert-butyl 1-(5-chloro-3-isobutyramido-1H-pyrrolo[2,3-b]pyridin-4-yl)piperidin-3-yl(methyl)carbamate (0.180 g, 51% yield).

Workup

  1. stirringthe reaction was stirred for 10 minutes
  2. customthe organic layer was separated
  3. customdried
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe crude residue was purified by reverse phase chromatography (Biotage SP4

Sources & evidence

ORD record
ord-275d2b13a39045edaca723db8c8488d2
Source dataset
uspto-grants-2015_03
Patent number
US08981085B2

Reaction notes

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