(R)-tert-butyl 1-(3-butyramido-5-chloro-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)butyramide

HRID 408377Notes

Reaction equation

HRID 408377 reaction equation
[C:1]([NH:6][C:7]1[C:15]2[C:10](=[N:11][CH:12]=[C:13]([Cl:30])[C:14]=2[N:16]2[CH2:21][CH2:20][CH2:19][C@@H:18]([NH:22]C(=O)OC(C)(C)C)[CH2:17]2)[NH:9][CH:8]=1)(=[O:5])[CH2:2][CH2:3][CH3:4]>C(O)(C(F)(F)F)=O>[NH2:22][C@@H:18]1[CH2:19][CH2:20][CH2:21][N:16]([C:14]2[C:13]([Cl:30])=[CH:12][N:11]=[C:10]3[NH:9][CH:8]=[C:7]([NH:6][C:1](=[O:5])[CH2:2][CH2:3][CH3:4])[C:15]=23)[CH2:17]1

Participants

3

Reactant 1

HCID 67045543(R)-tert-butyl 1-(3-butyramido-5-chloro-1H-pyrrolo[2,3-b]pyridin-4-yl)piperidin-3-ylcarbamate

Product 1

HCID 58195472(R)-N-(4-(3-aminopiperidin-1-yl)-5-chloro-1H-pyrrolo[2,3-b]pyridin-3-yl)butyramideYield 89.9%

Reagents, catalysts & solvents 1

HCID 6422Trifluoroacetic acidSolvent

Procedure

(R)-tert-Butyl 1-(3-butyramido-5-chloro-1H-pyrrolo[2,3-b]pyridin-4-yl)piperidin-3-ylcarbamate (221 mg, 0.507 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-chloro-1H-pyrrolo[2,3-b]pyridin-3-yl)butyramide (153 mg, 74% yield) as a solid. 1H NMR (400 MHz, (CD3)2SO) δ 11.83 (br s, 1H), 9.32 (s, 1H), 8.35 (br s, 2H), 8.13 (s, 1H), 7.57 (s, 1H), 3.54-3.46 (m, 1H), 3.45-3.30 (m, 2H), 3.27-3.04 (m, 2H), 2.41-2.34 (m, 2H), 2.18-2.09 (m, 1H), 1.91-1.79 (m, 1H), 1.72-1.59 (m, 3H), 1.59-1.39 (m, 1H), 0.96 (t, 3H). LCMS (APCI+) m/z 336.1, 338.1 (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-b2edc8000ca149e49bcf8d21aa837a83
Source dataset
uspto-grants-2014_06
Patent number
US08758830B2

Reaction notes

Loading…