Triethylamine → N-(3-methylpent-1-yn-3-yl)-6-amino-5-chloronicotinamide

HRID 583158

Reaction equation

HRID 583158 reaction equation
[NH2:1][C:2]1[C:10]([Cl:11])=[CH:9][C:5]([C:6]([OH:8])=O)=[CH:4][N:3]=1.C(N(CC)CC)C.CS(Cl)(=O)=O.Cl.[NH2:25][C:26]([CH3:31])([CH2:29][CH3:30])[C:27]#[CH:28]>O.O1CCCC1>[CH3:31][C:26]([NH:25][C:6](=[O:8])[C:5]1[CH:9]=[C:10]([Cl:11])[C:2]([NH2:1])=[N:3][CH:4]=1)([CH2:29][CH3:30])[C:27]#[CH:28]

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 31297Methanesulfonyl chlorideHCID 122329903-Methyl-1-pentyn-3-amine hydrochlorideHCID 143713816-Amino-5-chloropyridine-3-carboxylic acid

Product 1

HCID 17760200N-(3-methylpent-1-yn-3-yl)-6-amino-5-chloronicotinamideYield 43%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-30 °C

Procedure

In a 300 mL, three-necked, round-bottomed flask fitted with a mechanical stirrer, nitrogen inlet and thermometer were placed 5 g (0.03 mole) of 6-amino-5-chloronicotinic acid, 150 mL of tetrahydrofuran and 6.67 g (0.066 mole) of triethylamine. The resulting well-stirred mixture was cooled to -30° C. and 2.24 ml (0.03 mole) of methane sulfonyl chloride were added dropwise keeping the reaction temperature at -30° C. The resulting suspension was stirred at -30° C. during 30 minutes, after which 4.01 g (0.03 mole) of 3-amino-3-methyl-1-pentyne hydrochloride were added slowly over a 20 minute period. After the addition was completed, the reaction mixture was stirred at -30° C. for an additional 30 minutes. The reaction mixture was poured into water and extracted with methylene chloride (3×450 ml). The combined organic phases were washed with water (1×200 ml), and dried over anhydrous magnesium sulfate. The solvent was removed using a rotary evaporator, yielding the crude product. After purification by chromatographic column (silica gel, 1:1 ethyl acetate:hexane), 3.25 g N-(3-methylpent-1-yn-3-yl)-6-amino-5-chloronicotinamide were obtained as a white solid.

Workup

  1. customIn a 300 mL, three-necked, round-bottomed flask fitted with a mechanical stirrer, nitrogen inlet
  2. customat -30° C
  3. stirringThe resulting suspension was stirred at -30° C. during 30 minutes
  4. additionAfter the addition
  5. stirringthe reaction mixture was stirred at -30° C. for an additional 30 minutes
  6. extractionextracted with methylene chloride (3×450 ml)
  7. washThe combined organic phases were washed with water (1×200 ml)
  8. dry with materialdried over anhydrous magnesium sulfate
  9. customThe solvent was removed
  10. customa rotary evaporator
  11. customyielding the crude product
  12. customAfter purification by chromatographic column (silica gel, 1:1 ethyl acetate:hexane)

Sources & evidence

ORD record
ord-ae8981fa55214ebf8485018d832a8957
Source dataset
uspto-grants-1999_07
Patent number
US05929098

Linked notes

Loading…