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

HRID 408322Notes

Reaction equation

HRID 408322 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 #1 (70 mg, 0.11 mmol) in DCM (3 mL) at room temperature was treated with TFA (1 mL), and the reaction was stirred for 1 hour. The mixture was concentrated to dryness, and the resulting residue was purified by reverse phase HPLC (0-50% ACN in water). The product isolated was 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 #1 (50 mg, 84% yield). 1H NMR (400 MHz, D2O) δ 8.18 (s, 1H), 7.59 (s, 1H), 4.54-4.48 (m, 1H), 4.21-4.17 (m, 1H), 3.98-3.91 (m, 1H), 3.67-3.64 (m, 1H), 3.47-3.31 (m, 5H), 3.20-3.13 (m, 2H), 3.09-2.98 (m, 1H), 2.11-2.07 (m, 1H), 1.80-1.76 (m, 2H), 1.55-1.53 (m, 1H); LCMS (APCI+) m/z 423, 425 (M+H)+.

Workup

  1. concentrationThe mixture was concentrated to dryness
  2. customthe resulting residue was 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-1f9bf6e06980480b85f7ffad56dc3932
Source dataset
uspto-grants-2014_06
Patent number
US08758830B2

Reaction notes

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