Lithium Hydroxide → HCID 60205577, compound

HRID 408358Notes

Reaction equation

HRID 408358 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][C@@H:28]([CH3:32])[C:29](O)=[O:30].C1N(P(Cl)(N2C(=O)OCC2)=O)C(=O)OC1.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])[C@@H:28]([O:27][CH3:26])[CH3:32])=[CH:3][NH:4][C:5]2=[N:6][CH:7]=1

Participants

9

Reactant 5

HCID 3939Lithium HydroxideHCID 8471TriethylamineHCID 152842Bis(2-oxo-3-oxazolidinyl)phosphinic chlorideHCID 57025662-methoxypropanoic acid, (S)-HCID 67045610(R)-tert-butyl 1-(3-amino-5-chloro-1H-pyrrolo[2,3-b]pyridin-4-yl)piperidin-3-ylcarbamate

Product 1

HCID 60205577HCID 60205577, compoundYield 77%

Reagents, catalysts & solvents 3

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

Procedure

An NMP solution (2 mL) 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), (S)-2-methoxypropanoic acid (0.310 mL, 3.28 mmol), BOP-Cl (0.835 g, 3.28 mmol), and triethylamine (0.533 mL, 3.83 mmol) was stirred for 18 hours. 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 the product tert-butyl (R)-1-(5-chloro-3-((S)-2-methoxypropanamido)-1H-pyrrolo[2,3-b]pyridin-4-yl)piperidin-3-ylcarbamate (0.190 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-20724b489b95449fbbe1b9fd272cc39f
Source dataset
uspto-grants-2014_06
Patent number
US08758830B2

Reaction notes

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