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

HRID 1923874
Notes
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Reaction equation

HRID 1923874 reaction equation
[Cl:1][C:2]1[C:3]([N:17]2[CH2:22][CH2:21][CH2:20][C@@H:19]([NH:23]C(=O)OC(C)(C)C)[CH2:18]2)=[C:4]2[C:10]([NH:11][C:12]([CH:14]3[CH2:16][CH2:15]3)=[O:13])=[CH:9][NH:8][C:5]2=[N:6][CH:7]=1.Cl>C(O)(C(F)(F)F)=O.C(Cl)Cl.CCOCC>[ClH:1].[NH2:23][C@@H:19]1[CH2:20][CH2:21][CH2:22][N:17]([C:3]2[C:2]([Cl:1])=[CH:7][N:6]=[C:5]3[NH:8][CH:9]=[C:10]([NH:11][C:12]([CH:14]4[CH2:15][CH2:16]4)=[O:13])[C:4]=23)[CH2:18]1
ParticipantsProcedureWorkupSources & evidenceReaction notes

Participants

6

Reactant 2

HCID 313Hydrochloric AcidHCID 67045317(R)-tert-butyl 1-(5-chloro-3-(cyclopropanecarboxamido)-1H-pyrrolo[2,3-b]pyridin-4-yl)piperidin-3-ylcarbamate

Product 1

HCID 67045145(R)-N-(4-(3-aminopiperidin-1-yl)-5-chloro-1H-pyrrolo[2,3-b]pyridin-3-yl)cyclopropanecarboxamide hydrochlorideYield 138.1%

Reagents, catalysts & solvents 3

HCID 3283Diethyl EtherSolvent
HCID 6344
Dichloromethane
Solvent
HCID 6422Trifluoroacetic acidSolvent

Procedure

A solution of (R)-tert-butyl 1-(5-chloro-3-(cyclopropanecarboxamido)-1H-pyrrolo[2,3-b]pyridin-4-yl)piperidin-3-ylcarbamate (462 mg, 1.06 mmol) in neat TFA (4 mL) was stirred at room temperature for 30 minutes and concentrated in vacuo. The oily residue obtained was dissolved in CH2Cl2 (1 mL) and treated with 2M HCl in ether (4 mL). The resulting precipitate was evaporated from CH3CN (4×10 mL) to provide (R)-N-(4-(3-aminopiperidin-1-yl)-5-chloro-1H-pyrrolo[2,3-b]pyridin-3-yl)cyclopropanecarboxamide hydrochloride (271 mg, 63% yield) as a solid. 1H NMR (400 MHz, (CD3)2SO) δ 11.79 (d, 1H), 9.65 (s, 1H), 8.25 (br s, 3H), 8.11 (s, 1H), 7.48 (d, 1H), 3.53-3.48 (m, 1H), 3.44-3.31 (m, 2H), 3.23-3.11 (m, 2H), 2.13-2.08 (m, 1H), 1.89-1.80 (m, 2H), 1.75-1.70 (m, 1H), 1.54-1.45 (m, 1H0, 0.82 (d, 4H). LCMS (APCI+) m/z 334 (M+H)+.

Workup

  1. concentrationconcentrated in vacuo
  2. customThe oily residue obtained
  3. customThe resulting precipitate was evaporated from CH3CN (4×10 mL)

Sources & evidence

ORD record
ord-52597e41b7f24fec8ffeaa2742bcfb0b
Source dataset
uspto-grants-2012_05
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US08178131B2

Reaction notes

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On this pageParticipantsProcedureWorkupSources & evidenceReaction notes