Diisopropylethylamine → 5-chloro-N-[(1S)-1-cyclopropyl-2,2,2-trifluoroethyl]pyrazine-2-carboxamide

HRID 2363334Notes

Reaction equation

HRID 2363334 reaction equation
C(N(CC)C(C)C)(C)C.[Cl:10][C:11]1[N:12]=[CH:13][C:14]([C:17]([OH:19])=O)=[N:15][CH:16]=1.F[P-](F)(F)(F)(F)F.C[N+](C)=C(N(C)C)ON1C2N=CC=CC=2N=N1.Cl.[CH:45]1([C@H:48]([NH2:53])[C:49]([F:52])([F:51])[F:50])[CH2:47][CH2:46]1.C([O-])(O)=O.[Na+]>C(Cl)Cl>[Cl:10][C:11]1[N:12]=[CH:13][C:14]([C:17]([NH:53][C@@H:48]([CH:45]2[CH2:47][CH2:46]2)[C:49]([F:52])([F:51])[F:50])=[O:19])=[N:15][CH:16]=1

Participants

7

Reactant 5

HCID 81531DiisopropylethylamineHCID 4654725-Chloropyrazinoic acidHCID 516892Sodium BicarbonateHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 56595197(1S)-1-cyclopropyl-2,2,2-trifluoroethan-1-amine hydrochloride

Product 1

HCID 866757555-chloro-N-[(1S)-1-cyclopropyl-2,2,2-trifluoroethyl]pyrazine-2-carboxamideYield 72.9%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

N,N-Diisopropylethylamine (1.3 mL, 7.5 mmol) was added to a mixture of 5-chloropyrazine-2-carboxylic acid (0.40 g, 2.5 mmol), N,N,N′,N′-tetramethyl-O-(7-azabenzotriazol-1-yl)uronium hexafluorophosphate (1.0 g, 2.8 mmol) and (1S)-1-cyclopropyl-2,2,2-trifluoroethanamine hydrochloride (0.44 g, 2.5 mmol) (ASIBA Pharmatech, Cat. #: 70092-HCl) in methylene chloride (10 mL). The reaction mixture was stirred at room temperature overnight. The mixture was worked up with saturated aqueous NaHCO3, and extracted with ethyl acetate (3×20 mL). The combined organic layers were washed with brine, dried over MgSO4, filtered and concentrated under reduced pressure. The residue was purified by flash chromatography on a silica gel column with ethyl acetate in hexanes (0-20%) to afford the desired product (0.51 g, 72%). LCMS (M+H)+: m/z=280.0/282.0.

Workup

  1. extractionextracted with ethyl acetate (3×20 mL)
  2. washThe combined organic layers were washed with brine
  3. dry with materialdried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customThe residue was purified by flash chromatography on a silica gel column with ethyl acetate in hexanes (0-20%)

Sources & evidence

ORD record
ord-30412ff31fac4e1dad565b69cf85cea7
Source dataset
uspto-grants-2014_04
Patent number
US08691807B2

Reaction notes

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