Hydrochloric Acid → HCID 67045433, compound

HRID 2203874Notes

Reaction equation

HRID 2203874 reaction equation
[Br:1][C:2]1[C:3]([N:22]2[CH2:27][CH2:26][CH2:25][C@@H:24]([NH:28][CH2:29][CH2:30][O:31][Si](C(C)(C)C)(C)C)[CH2:23]2)=[C:4]2[C:10]([NH:11][C:12](=[O:21])[C:13]3[CH:18]=[CH:17][C:16]([F:19])=[C:15]([Cl:20])[CH:14]=3)=[CH:9][NH:8][C:5]2=[N:6][CH:7]=1.CCCC[N+](CCCC)(CCCC)CCCC.[F-].Cl>C1COCC1.C(Cl)Cl.CCOCC>[ClH:20].[Br:1][C:2]1[C:3]([N:22]2[CH2:27][CH2:26][CH2:25][C@@H:24]([NH:28][CH2:29][CH2:30][OH:31])[CH2:23]2)=[C:4]2[C:10]([NH:11][C:12](=[O:21])[C:13]3[CH:18]=[CH:17][C:16]([F:19])=[C:15]([Cl:20])[CH:14]=3)=[CH:9][NH:8][C:5]2=[N:6][CH:7]=1

Participants

7

Reactant 3

HCID 313Hydrochloric AcidHCID 2724141Tetrabutylammonium FluorideHCID 67045291HCID 67045291, compound

Product 1

HCID 67045433HCID 67045433, compoundYield 114.2%

Reagents, catalysts & solvents 3

HCID 3283Diethyl EtherSolventHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

A solution of (R)—N-(5-bromo-4-(3-(2-(tert-butyldimethylsilyloxy)ethylamino)piperidin-1-yl)-1H-pyrrolo[2,3-b]pyridin-3-yl)-3-chloro-4-fluorobenzamide (30 mg, 0.048 mmol) in THF (2 mL) at room temperature was treated with TBAF (0.048 mL, 0.048 mmol) and stirred for 10 minutes. The mixture was then concentrated in vacuo and purified by reverse phases HPLC (Gilson). The residue obtained was dissolved in a minimal amount of DCM and added to a stirring solution of 1M HCl in ether. The solid formed was filtered, washed with ether and dried to give (R)—N-(5-bromo-4-(3-(2-hydroxyethylamino)piperidin-1-yl)-1H-pyrrolo[2,3-b]pyridin-3-yl)-3-chloro-4-fluorobenzamide hydrochloride (0.015 g, 54% yield). 1H NMR (400 MHz, D2O) δ 8.19 (s, 1H), 7.98-7.94 (m, 1H), 7.82-7.76 (m, 1H), 7.38 (s, 1H), 7.34-7.29 (m, 1H), 3.64-3.61 (m, 2H), 3.42-2.94 (m, 7H), 1.90-1.82 (m, 1H), 1.70-1.62 (m, 1H), 1.44-1.36 (m, 2H); LCMS (APCI+) m/z 510, 512 (M+H)+.

Workup

  1. concentrationThe mixture was then concentrated in vacuo
  2. custompurified by reverse phases HPLC (Gilson)
  3. customThe residue obtained
  4. customThe solid formed
  5. filtrationwas filtered
  6. washwashed with ether
  7. customdried

Sources & evidence

ORD record
ord-e8996e5cbabd426e849c778279dd6947
Source dataset
uspto-grants-2016_06
Patent number
US09365568B2

Reaction notes

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