(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 2203945Notes

Reaction equation

HRID 2203945 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-b1d1860848b343d6bc754d82ed4f8fab
Source dataset
uspto-grants-2016_06
Patent number
US09365568B2

Reaction notes

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