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

HRID 1690792Notes

Reaction equation

HRID 1690792 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].F[P-](F)(F)(F)(F)F.C[N+](C)=C(N(C)C)ON1C2N=CC=CC=2N=N1.[F:42][C:43]([F:58])([F:57])[C:44]1[CH:53]=[CH:52][C:51]2[CH2:50][CH:49]([C:54](O)=[O:55])[CH2:48][CH2:47][C:46]=2[N:45]=1.C(N(CC)C(C)C)(C)C.CN1CCCC1=O>>[F:11][C:10]1[CH:9]=[C:8]([NH:12][S:13]([CH3:16])(=[O:15])=[O:14])[C:7]([CH3:17])=[CH:6][C:5]=1[C@H:3]([NH:2][C:54]([CH:49]1[CH2:48][CH2:47][C:46]2[N:45]=[C:44]([C:43]([F:58])([F:42])[F:57])[CH:53]=[CH:52][C:51]=2[CH2:50]1)=[O:55])[CH3:4]

Participants

6

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 581186312-(Trifluoromethyl)-5,6,7,8-tetrahydroquinoline-6-carboxylic acidHCID 66718598(R)-N-(4-(1-aminoethyl)-5-fluoro-2-methylphenyl)methanesulfonamide hydrochloride

Product 1

HCID 58118615N-((R)-1-(2-Fluoro-5-methyl-4-(methylsulfonamido)phenyl)ethyl)-2-(trifluoromethyl)-5,6,7,8-tetrahydroquinoline-6-carboxamideYield 73.9%

Procedure

A 2 mL vial was charged with (R)—N-(4-(1-aminoethyl)-5-fluoro-2-methylphenyl)methanesulfonamide hydrochloride (14 mg, 0.049 mmol) and N,N,N′,N′-tetramethyl-O-(7-azabenzotriazol-1-yl)uronium hexafluorophosphate (17 mg, 0.044 mmol). A solution of 2-(trifluoromethyl)-5,6,7,8-tetrahydroquinoline-6-carboxylic acid (6.0 mg, 0.024 mmol) and N,N-diisopropylethylamine (21 uL, 0.12 mmol) in N-methylpyrrolidinone (0.4 mL, 4 mmol) was added, and the mixture stirred to dissolution. After 40 min the mixture was filtered and purified by reverse-phase HPLC (10-75% MeCN in 10 mM Et2NH/H2O) to afford the amide as a solid (8.4 mg, 72%). 1H NMR (400 MHz, CD3OD) δ 7.73 (app t, J=8.3 Hz, 1H), 7.53 (dd, J=3.8, 8.0 Hz, 1H), 7.23 (d, J=8.3 Hz, 1H), 7.14 (dd, J=1.4, 11.7 Hz, 1H), 5.19 (app pentet, J=7.0 Hz, 1H), 3.17-2.94 (m, 4H), 2.98 (s, 3H), 2.82-2.71 (m, 1H), 2.32 (s, 3H), 2.23-2.12 (m, 1H), 2.07-1.89 (m, 1H), 1.47 (d, J=7.0 Hz, 3H); m/z=474.4 (M+H)+.

Workup

  1. filtrationAfter 40 min the mixture was filtered
  2. custompurified by reverse-phase HPLC (10-75% MeCN in 10 mM Et2NH/H2O)

Sources & evidence

ORD record
ord-c63425a2b1704e4c81baaf2443a5e9a6
Source dataset
uspto-grants-2012_04
Patent number
US08153651B2

Reaction notes

Loading…