N-methyl-2-pyrrolidone → 2-Acetyl-N-((R)-1-(2-fluoro-5-methyl-4-(methylsulfonamido)phenyl)ethyl)-5,6,7,8-tetrahydroquinoline-6-carboxamide

HRID 1690801Notes

Reaction equation

HRID 1690801 reaction equation
Cl.[NH2:2][C@@H:3]([C:5]1[C:10]([F:11])=[CH:9][C:8]([NH:12][S:13]([CH3:16])(=[O:15])=[O:14])=[C:7]([CH3:17])[CH:6]=1)[CH3:4].[C:18]([C:21]1[CH:30]=[CH:29][C:28]2[CH2:27][CH:26]([C:31](O)=[O:32])[CH2:25][CH2:24][C:23]=2[N:22]=1)(=[O:20])[CH3:19].F[P-](F)(F)(F)(F)F.C[N+](C)=C(N(C)C)ON1C2N=CC=CC=2N=N1.CN1CCCC1=O.C(N(CC)C(C)C)(C)C>CCOC(C)=O>[C:18]([C:21]1[CH:30]=[CH:29][C:28]2[CH2:27][CH:26]([C:31]([NH:2][C@@H:3]([C:5]3[CH:6]=[C:7]([CH3:17])[C:8]([NH:12][S:13]([CH3:16])(=[O:15])=[O:14])=[CH:9][C:10]=3[F:11])[CH3:4])=[O:32])[CH2:25][CH2:24][C:23]=2[N:22]=1)(=[O:20])[CH3:19]

Participants

7

Reactant 5

HCID 13387N-methyl-2-pyrrolidoneHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 581186172-Acetyl-5,6,7,8-tetrahydroquinoline-6-carboxylic acidHCID 66718598(R)-N-(4-(1-aminoethyl)-5-fluoro-2-methylphenyl)methanesulfonamide hydrochloride

Product 1

HCID 581186302-Acetyl-N-((R)-1-(2-fluoro-5-methyl-4-(methylsulfonamido)phenyl)ethyl)-5,6,7,8-tetrahydroquinoline-6-carboxamideYield 91.7%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
60 °C

Procedure

To a mixture of N-[4-((R)-1-Aminoethyl)-5-fluoro-2-methylphenyl]methanesulfonamide hydrochloride (55.3 mg, 0.195 mmol), 2-acetyl-5,6,7,8-tetrahydroquinoline-6-carboxylic acid (45 mg, 0.20 mmol) and N,N,N′,N′-Tetramethyl-O-(7-azabenzotriazol-1-yl)uronium Hexafluorophosphate (110 mg, 0.29 mmol) in N-Methylpyrrolidinone (192 uL, 1.99 mmol), N,N-Diisopropylethylamine (0.10 mL, 0.59 mmol) was added and the reaction was heated at 60° C. 4 h. The crude was diluted with EtOAc and washed with 1N HCl, 1M NaHCO3 and brine. The combined organic layers were dried (MgSO4), filtered and concentrated in vacuo to afford the title product (80 mg, 90%) as a brown oil that was used without further purification into the next step. m/z=448.4 (M+H)+.

Workup

  1. additionwas added
  2. custom4 h
  3. washwashed with 1N HCl, 1M NaHCO3 and brine
  4. dry with materialThe combined organic layers were dried (MgSO4)
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-dd5737f927464402bd7fcf0d3c1220f7
Source dataset
uspto-grants-2012_04
Patent number
US08153651B2

Reaction notes

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