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

HRID 25165
Notes
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Reaction equation

HRID 25165 reaction equation
[N:1]12[CH2:8][CH2:7][CH:4]([CH2:5][CH2:6]1)[C@@H:3]([NH:9][C:10]([C:12]1[N:13]=[CH:14][C:15]3[N:16]([C:18](Br)=[CH:19][CH:20]=3)[CH:17]=1)=[O:11])[CH2:2]2.[C:22]([OH:31])(=[O:30])[C@H:23]([C@@H:25]([C:27]([OH:29])=[O:28])[OH:26])[OH:24].[CH3:32][N:33](C=O)C>[C-]#N.[Zn+2].[C-]#N.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[C:27]([CH:25]([CH:23]([C:22]([OH:31])=[O:30])[OH:24])[OH:26])([OH:29])=[O:28].[N:1]12[CH2:8][CH2:7][CH:4]([CH2:5][CH2:6]1)[C@@H:3]([NH:9][C:10]([C:12]1[N:13]=[CH:14][C:15]3[N:16]([C:18]([C:32]#[N:33])=[CH:19][CH:20]=3)[CH:17]=1)=[O:11])[CH2:2]2
ParticipantsConditionsProcedureWorkupSources & evidenceReaction notes

Participants

6

Reactant 3

HCID 6228DimethylformamideHCID 439655D-Tartaric acidHCID 10247203N-[(3R)-1-azabicyclo[2.2.2]oct-3-yl]-6-bromopyrrolo[1,2-a]pyrazine-3-carboxamide

Product 1

HCID 69771933N-[(3R)-1-azabicyclo[2.2.2]oct-3-yl]-6-cyanopyrrolo[1,2-a]pyrazine-3-carboxamide TartrateYield 47%

Reagents, catalysts & solvents 2

HCID 11186
Zinc cyanide (Zn(CN)2)
Catalyst
HCID 178418397HCID 178418397, compoundCatalyst

Conditions

Temperature
95 °C

Procedure

To an argon sparged solution of N-[(3R)-1-azabicyclo[2.2.2]oct-3-yl]-6-bromopyrrolo[1,2-a]pyrazine-3-carboxamide (0.77 g, 2.14 mmol) in DMF (25 mL) is added zinc cyanide (0.26 g, 2.20 mmol), and tetrakis(triphenylphosphine)palladium (0) (0.25 g, 0.21 mmol). The resulting suspension is stirred at 95° C. for 48 h, then filtered through a pad of celite. The residue is purified using preparative chromatography (carried out on a Chiral OD column using a 40% IPA/heptanes each containing 0.1% diethylamine) to give a pale yellow oil that is salted with d-tartaric acid and crystallized from EtOH/Et2O to give a pale yellow solid. Yield 47%. HRMS (FAB) calcd for C16H17N5O+H 296.1511, found 296.1520.

Workup

  1. filtrationfiltered through a pad of celite
  2. customThe residue is purified
  3. customto give a pale yellow oil that
  4. customcrystallized from EtOH/Et2O
  5. customto give a pale yellow solid

Sources & evidence

ORD record
ord-35777fbdf51d4a96b2a0653b70a174ab
Source dataset
uspto-grants-2005_02
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US06858613B2

Reaction notes

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On this pageParticipantsConditionsProcedureWorkupSources & evidenceReaction notes