2-Pyrazinecarboxylic acid → N-(5-(Hydroxymethyl)bicyclo[3.2.1]octan-1-yl)pyrazine-2-carboxamide

HRID 1503250Notes

Reaction equation

HRID 1503250 reaction equation
[NH2:1][C:2]12[CH2:9][C:6]([CH2:10][OH:11])([CH2:7][CH2:8]1)[CH2:5][CH2:4][CH2:3]2.[N:12]1[CH:17]=[CH:16][N:15]=[CH:14][C:13]=1[C:18](O)=[O:19].CCN(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>[OH:11][CH2:10][C:6]12[CH2:9][C:2]([NH:1][C:18]([C:13]3[CH:14]=[N:15][CH:16]=[CH:17][N:12]=3)=[O:19])([CH2:8][CH2:7]1)[CH2:3][CH2:4][CH2:5]2

Participants

6

Reactant 4

HCID 10472-Pyrazinecarboxylic acidHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 84072201(5-Aminobicyclo[3.2.1]octan-1-yl)methanol

Product 1

HCID 117702464N-(5-(Hydroxymethyl)bicyclo[3.2.1]octan-1-yl)pyrazine-2-carboxamideYield 100%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of (5-aminobicyclo[3.2.1]octan-1-yl)methanol (327 g, 2.1 mmol) and pyrazine-2-carboxylic acid (260 mg, 2.1 mmol) in DMF (10 mL) was added DIEA (680 mg, 5.22 mmol), followed by HATU (800 mg, 2.1 mmol). After stirring at room temperature for an hour, the reaction mixture was quenched with water (25 mL) and extracted with ethyl acetate (3×25 mL). The combined organic phase was washed with brine, dried over Na2SO4 and concentrated under rescued pressure to give a residue, which was purified by column chromatography (silica gel, petroleum ether/ethyl acetate=2/1) to afford 540 mg (100%) of the title compound, N-(5-(hydroxymethyl)bicyclo[3.2.1]octan-1-yl)pyrazine-2-carboxamide as a colorless oil. ESI-MS m/z: 262 (M+H)+.

Workup

  1. customthe reaction mixture was quenched with water (25 mL)
  2. extractionextracted with ethyl acetate (3×25 mL)
  3. washThe combined organic phase was washed with brine
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated under rescued pressure
  6. customto give a residue, which
  7. customwas purified by column chromatography (silica gel, petroleum ether/ethyl acetate=2/1)

Sources & evidence

ORD record
ord-4724b363d932428797b21574dc1aa803
Source dataset
uspto-grants-2015_12
Patent number
US09212165B2

Reaction notes

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