Hydrochloric Acid → (S)-1-(4-(5-chloro-1H-pyrazolo[3,4-b]pyridin-4-yl)piperazin-1-yl)-2-(4-chlorophenyl)-2-((S)-pyrrolidin-2-yl)ethanone dihydrochloride

HRID 387605Notes

Reaction equation

HRID 387605 reaction equation
[ClH:1].[Cl:2][C:3]1[C:4]([N:12]2[CH2:17][CH2:16][N:15]([C:18](=[O:39])[C@H:19]([C@@H:27]3[CH2:31][CH2:30][CH2:29][N:28]3C(OC(C)(C)C)=O)[C:20]3[CH:25]=[CH:24][C:23]([Cl:26])=[CH:22][CH:21]=3)[CH2:14][CH2:13]2)=[C:5]2[CH:11]=[N:10][NH:9][C:6]2=[N:7][CH:8]=1>O1CCOCC1.C(Cl)Cl>[ClH:2].[ClH:1].[Cl:2][C:3]1[C:4]([N:12]2[CH2:13][CH2:14][N:15]([C:18](=[O:39])[C@@H:19]([C:20]3[CH:25]=[CH:24][C:23]([Cl:26])=[CH:22][CH:21]=3)[C@@H:27]3[CH2:31][CH2:30][CH2:29][NH:28]3)[CH2:16][CH2:17]2)=[C:5]2[CH:11]=[N:10][NH:9][C:6]2=[N:7][CH:8]=1

Participants

5

Reactant 2

HCID 313Hydrochloric AcidHCID 68762062HCID 68762062, compound

Product 1

HCID 68764139(S)-1-(4-(5-chloro-1H-pyrazolo[3,4-b]pyridin-4-yl)piperazin-1-yl)-2-(4-chlorophenyl)-2-((S)-pyrrolidin-2-yl)ethanone dihydrochlorideYield 83%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 312751,4-DioxaneSolvent

Procedure

4N HCl in dioxane (2 mL) was added to a solution of (S)-tert-butyl 2-((S)-2-(4-(5-chloro-1H-pyrazolo[3,4-b]pyridin-4-yl)piperazin-1-yl)-1-(4-chlorophenyl)-2-oxoethyl)pyrrolidine-1-carboxylate (90 mg, 0.16 mmol) in CH2Cl2 (1 ml). The mixture was stirred at room temperature for 30 minutes. After 30 minutes, the solvent was removed in vacuo, and the resulting residue was triturated with ether. The solid material was filtered, washed with additional ether (2×2 mL) and dried to provide (S)-1-(4-(5-chloro-1H-pyrazolo[3,4-b]pyridin-4-yl)piperazin-1-yl)-2-(4-chlorophenyl)-2-((S)-pyrrolidin-2-yl)ethanone dihydrochloride (71 mg, 0.13 mmol, 83% yield) as a cream solid. LCMS (APCI+) m/z 459.1, 461.1 [(M+H]+. NMR (400 Hz, DMSO-d6) δ 9.61 (br s, 1H), 9.08 (br s, 1H), 8.30 (s, 1H), 8.19 (s, 1H), 7.49 (d, 2H), 7.44 (d, 2H), 4.53 (d, 1H), 4.03-3.96 (m, 1H), 3.79-3.70 (m, 3H), 3.69-3.57 (m, 3H), 3.51-3.45 (m, 1H), 3.21-3.14 (m, 2H), 3.09-3.00 (m, 1H), 1.97-1.89 (m, 1H), 1.78-1.71 (m, 1H), 1.63-1.52 (m, 2H).

Workup

  1. waitAfter 30 minutes
  2. customthe solvent was removed in vacuo
  3. customthe resulting residue was triturated with ether
  4. filtrationThe solid material was filtered
  5. washwashed with additional ether (2×2 mL)
  6. customdried

Sources & evidence

ORD record
ord-27b46c88d8f64bfa920cca9d67a2a198
Source dataset
uspto-grants-2013_02
Patent number
US08372842B2

Reaction notes

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