HomeMCPWorkbenchSkills
HomeWorkbenchNotificationsMe
llms.txt · MCP GuidePrivacy Policy · Terms of Service · Supportv1.8.0
  1. Home
  2. /Reaction

Dichloromethane → (R)-N-(4-(3-aminopiperidin-1-yl)-5-bromo-1H-pyrrolo[2,3-b]pyridin-3-yl)-1-methyl-6-oxo-1,6-dihydropyridine-3-carboxamide hydrochloride

HRID 875691
Notes
Print preview

Reaction equation

HRID 875691 reaction equation
[Br:1][C:2]1[C:3](F)=[C:4]2[C:10]([NH:11][C:12]([C:14]3[CH:19]=[CH:18][C:17](=[O:20])[N:16]([CH3:21])[CH:15]=3)=[O:13])=[CH:9][NH:8][C:5]2=[N:6][CH:7]=1.[NH:23]1[CH2:28][CH2:27][CH2:26][C@@H:25]([NH:29]C(=O)OC(C)(C)C)[CH2:24]1.C(O)(C(F)(F)F)=O.C(Cl)[Cl:45]>CCCCO>[ClH:45].[NH2:29][C@@H:25]1[CH2:26][CH2:27][CH2:28][N:23]([C:3]2[C:2]([Br:1])=[CH:7][N:6]=[C:5]3[NH:8][CH:9]=[C:10]([NH:11][C:12]([C:14]4[CH:19]=[CH:18][C:17](=[O:20])[N:16]([CH3:21])[CH:15]=4)=[O:13])[C:4]=23)[CH2:24]1
ParticipantsProcedureWorkupSources & evidenceReaction notes

Participants

6

Reactant 4

HCID 6344DichloromethaneHCID 6422Trifluoroacetic acidHCID 1514172(3R)-3-Aminopiperidine, 3-BOC protectedHCID 60205343N-(5-bromo-4-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl)-1-methyl-6-oxo-1,6-dihydropyridine-3-carboxamide

Product 1

HCID 67045381(R)-N-(4-(3-aminopiperidin-1-yl)-5-bromo-1H-pyrrolo[2,3-b]pyridin-3-yl)-1-methyl-6-oxo-1,6-dihydropyridine-3-carboxamide hydrochloride
Yield 36%

Reagents, catalysts & solvents 1

HCID 2631-ButanolSolvent

Procedure

N-(5-Bromo-4-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl)-1-methyl-6-oxo-1,6-dihydropyridine-3-carboxamide (0.22 g, 0.602 mmol) and (R)-tert-butyl piperidin-3-ylcarbamate (0.362 g, 1.81 mmol) in n-BuOH (2 mL) were stirred at 143° C. (bath) for 24 hours. The solvent was removed, and the residue was dissolved in ethyl acetate (20 mL), washed with water (10 mL), brine (10 mL) and dried over sodium sulfate. After removal of the solvent, the residue was purified by C-18 reverse phase flash chromatography (Biotage SP4 unit, C-18 25M column, 10-80% CH3CN/water gradient; 30 CV) to give a solid. This solid was dissolved in DCM (3 mL), and TFA (0.5 mL) was added. The mixture was stirred at room temperature for 1 hour. The solvent was removed. The residue was dissolved in DCM (1 mL), and 2N HCl in ether (3 mL) was added. The solid formed was collected by filtration to give (R)—N-(4-(3-aminopiperidin-1-yl)-5-bromo-1H-pyrrolo[2,3-b]pyridin-3-yl)-1-methyl-6-oxo-1,6-dihydropyridine-3-carboxamide hydrochloride (0.113 g, 36% yield) as a solid. 1H NMR (400 MHz, (CD3)2SO) δ 11.94 (s, 1H), 9.74 (s, 1H), 8.62 (s, 8.25 (s, 1H), 8.15 (br s, 3H), 8.06 (d, 1H), 7.51 (s, 1H), 6.49 (d, 1H), 3.44 (m, 1H), 3.32 (m, 1H), 3.20 (m, 2H), 3.07 (m, 1H), 1.93 (m, 1H), 1.66 (m, 1H), 1.49 (m, 1H), 1.35 (m, 1H); LCMS (APCI+) m/z 445 (M+H)+.

Workup

  1. customThe solvent was removed
  2. dissolutionthe residue was dissolved in ethyl acetate (20 mL)
  3. washwashed with water (10 mL), brine (10 mL)
  4. dry with materialdried over sodium sulfate
  5. customAfter removal of the solvent
  6. customthe residue was purified by C-18 reverse phase flash chromatography (Biotage SP4 unit
  7. custom30 CV) to give a solid
  8. customThe solvent was removed
  9. dissolutionThe residue was dissolved in DCM (1 mL)
  10. addition2N HCl in ether (3 mL) was added
  11. customThe solid formed
  12. filtrationwas collected by filtration

Sources & evidence

ORD record
ord-4632c2287f3b441a8822fa5df3a6b507
Source dataset
uspto-grants-2015_03
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US08981085B2

Reaction notes

Loading…

On this pageParticipantsProcedureWorkupSources & evidenceReaction notes