(R)-tert-butyl 1-(5-chloro-3-(2-hydroxy-2-methylpropanamido)-1H-pyrrolo[2,3-b]pyridin-4-yl)piperidin-3-ylcarbamate → (R)-N-(4-(3-aminopiperidin-1-yl)-5-chloro-1H-pyrrolo[2,3-b]pyridin-3-yl)-2-hydroxy-2-methylpropanamide hydrochloride

HRID 408368Notes

Reaction equation

HRID 408368 reaction equation
[Cl:1][C:2]1[C:3]([N:18]2[CH2:23][CH2:22][CH2:21][C@@H:20]([NH:24]C(=O)OC(C)(C)C)[CH2:19]2)=[C:4]2[C:10]([NH:11][C:12](=[O:17])[C:13]([OH:16])([CH3:15])[CH3:14])=[CH:9][NH:8][C:5]2=[N:6][CH:7]=1>FC(F)(F)C(O)=O>[ClH:1].[NH2:24][C@@H:20]1[CH2:21][CH2:22][CH2:23][N:18]([C:3]2[C:2]([Cl:1])=[CH:7][N:6]=[C:5]3[NH:8][CH:9]=[C:10]([NH:11][C:12](=[O:17])[C:13]([OH:16])([CH3:14])[CH3:15])[C:4]=23)[CH2:19]1

Participants

3

Reactant 1

HCID 67045520(R)-tert-butyl 1-(5-chloro-3-(2-hydroxy-2-methylpropanamido)-1H-pyrrolo[2,3-b]pyridin-4-yl)piperidin-3-ylcarbamate

Product 1

HCID 67045257(R)-N-(4-(3-aminopiperidin-1-yl)-5-chloro-1H-pyrrolo[2,3-b]pyridin-3-yl)-2-hydroxy-2-methylpropanamide hydrochlorideYield 108.5%

Reagents, catalysts & solvents 1

HCID 6422Trifluoroacetic acidSolvent

Procedure

(R)-tert-Butyl 1-(5-chloro-3-(2-hydroxy-2-methylpropanamido)-1H-pyrrolo[2,3-b]pyridin-4-yl)piperidin-3-ylcarbamate (221 mg, 0.489 mmol) was stirred in trifluoroacetic acid (3 mL) at room temperature for 1.5 hours. The solvent was evaporated in vacuo, and the residue was purified by reverse phase chromatography (Biotage SP4, C-18 25M+, 2-55% CH3CN/water, 25CV). The isolated product was taken up in a minimal volume of methanol and added to a stirred solution of 2N HCl-Et2O. The salt formed was collected by filtration, washed with acetonitrile and dried under vacuum to give (R)—N-(4-(3-aminopiperidin-1-yl)-5-chloro-1H-pyrrolo[2,3-b]pyridin-3-yl)-2-hydroxy-2-methylpropanamide hydrochloride (103 mg, 50% yield) as a solid. 1H NMR (400 MHz, D2O) δ 8.05 (s, 1H), 7.53 (s, 1H), 3.64-3.48 (m, 2H), 3.53-3.22 (m, 1H), 3.24-3.16 (m, 1H), 3.12-3.04 (m, 1H), 2.12-2.04 (m, 1H), 1.80-1.66 (m, 2H), 1.56-1.44 (m, 1H), 1.38 (s, 3H), 1.35 (s, 3H). LCMS (APCI+) m/z 352.1, 354.1 (M+H)+, Retention time=2.02 minutes.

Workup

  1. customThe solvent was evaporated in vacuo
  2. customthe residue was purified by reverse phase chromatography (Biotage SP4
  3. additionadded to a stirred solution of 2N HCl-Et2O
  4. customThe salt formed
  5. filtrationwas collected by filtration
  6. washwashed with acetonitrile
  7. customdried under vacuum

Sources & evidence

ORD record
ord-7fe87390afcc449b969c7eb3eefbcc6f
Source dataset
uspto-grants-2014_06
Patent number
US08758830B2

Reaction notes

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