Dichloromethane → (R)-N-(4-(3-aminopiperidin-1-yl)-5-bromo-1H-pyrrolo[2,3-b]pyridin-3-yl)propionamide hydrochloride

HRID 1923901Notes

Reaction equation

HRID 1923901 reaction equation
[Br:1][C:2]1[C:3]([N:16]2[CH2:21][CH2:20][CH2:19][C@@H:18]([NH:22]C(=O)OC(C)(C)C)[CH2:17]2)=[C:4]2[C:10]([NH:11][C:12](=[O:15])[CH2:13][CH3:14])=[CH:9][NH:8][C:5]2=[N:6][CH:7]=1.C(O)(C(F)(F)F)=O.C(Cl)[Cl:38]>>[ClH:38].[NH2:22][C@@H:18]1[CH2:19][CH2:20][CH2:21][N:16]([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:15])[CH2:13][CH3:14])[C:4]=23)[CH2:17]1

Participants

4

Reactant 3

HCID 6344DichloromethaneHCID 6422Trifluoroacetic acidHCID 67045151(R)-tert-butyl 1-(5-bromo-3-propionamido-1H-pyrrolo[2,3-b]pyridin-4-yl)piperidin-3-ylcarbamate

Product 1

HCID 67045120(R)-N-(4-(3-aminopiperidin-1-yl)-5-bromo-1H-pyrrolo[2,3-b]pyridin-3-yl)propionamide hydrochlorideYield 77.9%

Procedure

(R)-tert-butyl 1-(5-bromo-3-propionamido-1H-pyrrolo[2,3-b]pyridin-4-yl)piperidin-3-ylcarbamate (0.150 g, 0.322 mmol) was placed in DCM (3 mL) at room temperature. TFA (1 mL) was then added. The reaction was stirred at room temperature for 1 hour and concentrated to dryness. The resulting residue was then purified by reverse phase HPLC (0-50% ACN in water). The resulting product was next dissolved in minimal DCM (with MeOH to aid solubility) and added to a stirring solution of 1M HCl in ether. The resulting solid was filtered, washed with ether and dried to give (R)-N-(4-(3-aminopiperidin-1-yl)-5-bromo-1H-pyrrolo[2,3-b]pyridin-3-yl)propionamide hydrochloride (0.110 g, 77.9% yield). 1H NMR (400 MHz, D2O) δ 8.24 (s, 1H), 7.27 (s, 1H), 3.74-3.71 (m, 1H), 3.56-3.52 (m, 1H), 3.33-3.30 (m, 1H), 3.20-3.15 (m, 2H), 2.42-2.37 (q, 2H), 2.08-2.06 (m, 1H), 1.80-1.76 (m, 1H), 1.67-1.54 (m, 2H), 1.10-1.06 (t, 3H). LCMS (APCI+) m/z 366, 368 (M+H)+.

Workup

  1. concentrationconcentrated to dryness
  2. customThe resulting residue was then purified by reverse phase HPLC (0-50% ACN in water)
  3. dissolutionThe resulting product was next dissolved in minimal DCM (with MeOH to aid solubility)
  4. additionadded to a stirring solution of 1M HCl in ether
  5. filtrationThe resulting solid was filtered
  6. washwashed with ether
  7. customdried

Sources & evidence

ORD record
ord-d57ff62c9f774cb7a3bbf4561afa4904
Source dataset
uspto-grants-2012_05
Patent number
US08178131B2

Reaction notes

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