Hydrochloric Acid → N-(4-((R)-3-aminopiperidin-1-yl)-5-bromo-1H-pyrrolo[2,3-b]pyridin-3-yl)morpholine-2-carboxamide hydrochloride

HRID 875810Notes

Reaction equation

HRID 875810 reaction equation
[Br:1][C:2]1[C:3]([N:27]2[CH2:32][CH2:31][CH2:30][C@@H:29]([NH:33]C(OC(C)(C)C)=O)[CH2:28]2)=[C:4]2[C:10]([NH:11][C:12]([CH:14]3[O:19][CH2:18][CH2:17][N:16](C(OC(C)(C)C)=O)[CH2:15]3)=[O:13])=[CH:9][NH:8][C:5]2=[N:6][CH:7]=1.C(O)(C(F)(F)F)=O.[ClH:48]>C(Cl)Cl.CCOCC>[ClH:48].[NH2:33][C@@H:29]1[CH2:30][CH2:31][CH2:32][N:27]([C:3]2[C:2]([Br:1])=[CH:7][N:6]=[C:5]3[NH:8][CH:9]=[C:10]([NH:11][C:12]([CH:14]4[O:19][CH2:18][CH2:17][NH:16][CH2:15]4)=[O:13])[C:4]=23)[CH2:28]1

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 6422Trifluoroacetic acidHCID 60205509tert-butyl 2-(5-bromo-4-((R)-3-(tert-butoxycarbonylamino)piperidin-1-yl)-1H-pyrrolo[2,3-b]pyridin-3-ylcarbamoyl)morpholine-4-carboxylate

Product 1

HCID 60205510N-(4-((R)-3-aminopiperidin-1-yl)-5-bromo-1H-pyrrolo[2,3-b]pyridin-3-yl)morpholine-2-carboxamide hydrochloride

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 6344DichloromethaneSolvent2×

Procedure

A solution of tert-butyl 2-(5-bromo-4-((R)-3-(tert-butoxycarbonylamino)piperidin-1-yl)-1H-pyrrolo[2,3-b]pyridin-3-ylcarbamoyl)morpholine-4-carboxylate diastereomer #2 (80 mg, 0.13 mmol) in DCM (3 mL) at room temperature was treated with TFA (1 mL). The mixture 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 product isolated 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 N-(4-((R)-3-aminopiperidin-1-yl)-5-bromo-1H-pyrrolo[2,3-b]pyridin-3-yl)morpholine-2-carboxamide hydrochloride diastereomer #2 (44 mg, 64% yield). 1H NMR (400 MHz, D2O) δ 8.18 (s, 1H), 7.57 (s, 1H), 4.55-4.51 (m, 1H), 4.20-4.16 (m, 1H), 3.97-3.90 (m, 1H), 3.67-3.64 (m, 1H), 3.49-3.29 (m, 5H), 3.20-3.08 (m, 2H), 2.95-2.92 (m, 2.09-2.06 (m, 1H), 1.81-1.69 (m, 2H), 1.53-1.49 (m, 1H); LCMS (APCI+) m/z 423, 425 (M+H)+.

Workup

  1. concentrationconcentrated to dryness
  2. customThe resulting residue was then purified by reverse phase HPLC (0-50% ACN in water)
  3. customThe product isolated
  4. filtrationThe resulting solid was filtered
  5. washwashed with ether
  6. customdried

Sources & evidence

ORD record
ord-d85b351654c7481ab9e1c2a92d4c69d3
Source dataset
uspto-grants-2015_03
Patent number
US08981085B2

Reaction notes

Loading…