(R)-tert-butyl 1-(5-bromo-3-butyramido-1H-pyrrolo[2,3-b]pyridin-4-yl)piperidin-3-ylcarbamate → (R)-N-(4-(3-aminopiperidin-1-yl)-5-bromo-1H-pyrrolo[2,3-b]pyridin-3-yl)butyramide

HRID 2203929Notes

Reaction equation

HRID 2203929 reaction equation
[Br:1][C:2]1[C:3]([N:17]2[CH2:22][CH2:21][CH2:20][C@@H:19]([NH:23]C(=O)OC(C)(C)C)[CH2:18]2)=[C:4]2[C:10]([NH:11][C:12](=[O:16])[CH2:13][CH2:14][CH3:15])=[CH:9][NH:8][C:5]2=[N:6][CH:7]=1>C(O)(C(F)(F)F)=O>[NH2:23][C@@H:19]1[CH2:20][CH2:21][CH2:22][N:17]([C:3]2[C:2]([Br:1])=[CH:7][N:6]=[C:5]3[NH:8][CH:9]=[C:10]([NH:11][C:12](=[O:16])[CH2:13][CH2:14][CH3:15])[C:4]=23)[CH2:18]1

Participants

3

Reactant 1

HCID 67045202(R)-tert-butyl 1-(5-bromo-3-butyramido-1H-pyrrolo[2,3-b]pyridin-4-yl)piperidin-3-ylcarbamate

Product 1

HCID 44515040(R)-N-(4-(3-aminopiperidin-1-yl)-5-bromo-1H-pyrrolo[2,3-b]pyridin-3-yl)butyramideYield 79%

Reagents, catalysts & solvents 1

HCID 6422Trifluoroacetic acidSolvent

Procedure

(R)-tert-Butyl 1-(5-bromo-3-butyramido-1H-pyrrolo[2,3-b]pyridin-4-yl)piperidin-3-ylcarbamate (176 mg, 0.366 mmol) was stirred in TFA (3 mL) at room temperature for 1.5 hours. The solvent was evaporated in vacuo, and the residue purified by reverse phase chromatography (Biotage SP4, C-18 12M+, 2-50% CH3CN/water, 16CV). 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-bromo-1H-pyrrolo[2,3-b]pyridin-3-yl)butyramide (110 mg, 66% yield) as a solid. 1H NMR (400 MHz, D2O) δ 8.27 (s, 1H), 7.54 (s, 1H), 3.52-3.23 (m, 4H), 3.15-3.05 (m, 1H), 2.38 (t, 2H), 2.19-2.10 (m, 1H), 1.93-1.85 (m, 1H), 1.78-1.60 (m, 3H), 1.58-1.42 (m, 1H), 0.97 (t, 3H). LCMS (APCI+) m/z 380, 383.1 (M+H)+, Retention time=2.38 minutes.

Workup

  1. customThe solvent was evaporated in vacuo
  2. customthe residue 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-c9cfe35f00ba42eaa05086a3f637c875
Source dataset
uspto-grants-2016_06
Patent number
US09365568B2

Reaction notes

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