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

HRID 1034841Notes

Reaction equation

HRID 1034841 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.[CH3:26][O:27][CH2:28][C:29](Cl)=[O:30].C(N(CC)CC)C.[Li+].[OH-]>CC#N.O.O.CN1C(=O)CCC1>[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:29](=[O:30])[CH2:28][O:27][CH3:26])=[CH:3][NH:4][C:5]2=[N:6][CH:7]=1

Participants

8

Reactant 4

HCID 3939Lithium HydroxideHCID 8471TriethylamineHCID 96623Methoxyacetyl chlorideHCID 67045610(R)-tert-butyl 1-(3-amino-5-chloro-1H-pyrrolo[2,3-b]pyridin-4-yl)piperidin-3-ylcarbamate

Product 1

HCID 67045237(R)-tert-butyl 1-(5-chloro-3-(2-methoxyacetamido)-1H-pyrrolo[2,3-b]pyridin-4-yl)piperidin-3-ylcarbamateYield 77.2%

Reagents, catalysts & solvents 3

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

Procedure

An NMP (2 mL) solution of (R)-tert-butyl 1-(3-amino-5-chloro-1H-pyrrolo[2,3-b]pyridin-4-yl)piperidin-3-ylcarbamate (0.200 g, 0.547 mmol; Example 91, Step A), 2-methoxyacetyl chloride (0.302 mL, 3.28 mmol), and triethylamine (0.533 mL, 3.83 mmol) was stirred at room temperature for 1 hour. 3M aqueous LiOH (3 mL) was then added. The reaction was stirred for 10 minutes, poured into water, and extracted with DCM. The combined organic fractions were dried (MgSO4), filtered, and concentrated to give the crude product, which was purified by reverse phase chromatography (Biotage SP4, C-18 25M+, 5-95 CH3CN/water) to give (R)-tert-butyl 1-(5-chloro-3-(2-methoxyacetamido)-1H-pyrrolo[2,3-b]pyridin-4-yl)piperidin-3-ylcarbamate (0.185 g, 77% yield).

Workup

  1. extractionextracted with DCM
  2. dry with materialThe combined organic fractions were dried (MgSO4)
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customto give the crude product, which
  6. customwas purified by reverse phase chromatography (Biotage SP4

Sources & evidence

ORD record
ord-76c062eec8274f89a8431fedcfbe831a
Source dataset
uspto-grants-2013_10
Patent number
US08545897B2

Reaction notes

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