Diisopropylethylamine → N-[(3R)-1-azabicyclo[2.2.2]oct-3-yl]-6-bromopyrrolo[1,2-a]pyrazine-3-carboxamide

HRID 25162

Reaction equation

HRID 25162 reaction equation
Cl.[Br:2][C:3]1[N:7]2[CH:8]=[C:9]([C:12]([OH:14])=O)[N:10]=[CH:11][C:6]2=[CH:5][CH:4]=1.[C:15]1([NH2:26])[C:20](F)=[C:19](F)[C:18](F)=[C:17](N)C=1F.Cl.Cl.[CH3:29][CH2:30][N:31](C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C.C1COCC1>[N:26]12[CH2:17][CH2:18][CH:19]([CH2:20][CH2:15]1)[C@@H:30]([NH:31][C:12]([C:9]1[N:10]=[CH:11][C:6]3[N:7]([C:3]([Br:2])=[CH:4][CH:5]=3)[CH:8]=1)=[O:14])[CH2:29]2

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 149026Tetrafluoro-m-phenylenediamine dihydrochlorideHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 69713212588720-63-2

Product 1

HCID 10247203N-[(3R)-1-azabicyclo[2.2.2]oct-3-yl]-6-bromopyrrolo[1,2-a]pyrazine-3-carboxamide

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a suspension of 6-bromopyrrolo[1,2-a]pyrazine-3-carboxylic acid hydrochloride (1.67 mmol), (R)-3-aminoquinulidine dihydrochloride (0.34 g, 1.67 mmol), DIEA (1.5 mL, 8.35 mmol) in DMF (20 mL) and THF (10 mL) is added HATU (0.64 g, 1.67 mmol). The resulting suspension is stirred for 16 h at which time it is concentrated to dryness under reduced pressure. The resulting material is absorbed to silica gel and purified with silica gel chromatography (9% MeOH/1%NH3OH/CH2Cl2 as the eluent) salted with fumeric acid, and crystallized from EtOH/acetone/Et2O to give an off white spheres. Yield 45%. HRMS (FAB) calcd. for C15H17BrN4O+H 349.0664, found 349.0647.

Workup

  1. concentrationis concentrated to dryness under reduced pressure
  2. customThe resulting material is absorbed to silica gel
  3. custompurified with silica gel chromatography (9% MeOH/1%NH3OH/CH2Cl2 as the eluent)
  4. customcrystallized from EtOH/acetone/Et2O
  5. customto give an off white spheres

Sources & evidence

ORD record
ord-719641f08ec94b06a39361fb8608fa61
Source dataset
uspto-grants-2005_02
Patent number
US06858613B2

Linked notes

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