Diisopropylethylamine → N-((R)-1-(2-Fluoro-5-methyl-4-(methylsulfonamido)phenyl)ethyl)-2-(1,1,1-trifluoro-2-methylpropan-2-yl)-5,6,7,8-tetrahydroquinoline-6-carboxamide

HRID 1690785Notes

Reaction equation

HRID 1690785 reaction equation
F[P-](F)(F)(F)(F)F.C[N+](C)=C(N(C)C)ON1C2N=CC=CC=2N=N1.C(N(CC)C(C)C)(C)C.[F:34][C:35]([F:53])([F:52])[C:36]([C:39]1[CH:48]=[CH:47][C:46]2[CH2:45][C@H:44]([C:49]([OH:51])=O)[CH2:43][CH2:42][C:41]=2[N:40]=1)([CH3:38])[CH3:37].Cl.[NH2:55][C@@H:56]([C:58]1[C:63]([F:64])=[CH:62][C:61]([NH:65][S:66]([CH3:69])(=[O:68])=[O:67])=[C:60]([CH3:70])[CH:59]=1)[CH3:57]>CN1CCCC1=O>[F:64][C:63]1[CH:62]=[C:61]([NH:65][S:66]([CH3:69])(=[O:68])=[O:67])[C:60]([CH3:70])=[CH:59][C:58]=1[C@H:56]([NH:55][C:49]([CH:44]1[CH2:43][CH2:42][C:41]2[N:40]=[C:39]([C:36]([CH3:38])([CH3:37])[C:35]([F:53])([F:34])[F:52])[CH:48]=[CH:47][C:46]=2[CH2:45]1)=[O:51])[CH3:57]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 58118632(R)-2-(1,1,1-trifluoro-2-methylpropan-2-yl)-5,6,7,8-tetrahydroquinoline-6-carboxylic acidHCID 66718598(R)-N-(4-(1-aminoethyl)-5-fluoro-2-methylphenyl)methanesulfonamide hydrochloride

Product 1

HCID 58118612N-((R)-1-(2-Fluoro-5-methyl-4-(methylsulfonamido)phenyl)ethyl)-2-(1,1,1-trifluoro-2-methylpropan-2-yl)-5,6,7,8-tetrahydroquinoline-6-carboxamideYield 46%

Reagents, catalysts & solvents 1

HCID 13387N-methyl-2-pyrrolidoneSolvent2×

Procedure

A solution of N,N,N′,N′-tetramethyl-O-(7-azabenzotriazol-1-yl)uronium hexafluorophosphate (19.8 mg, 0.0522 mmol) and N,N-diisopropylethylamine (28 uL, 0.16 mmol) in N-methylpyrrolidinone (300 uL) was added to (R)-2-(1,1,1-trifluoro-2-methylpropan-2-yl)-5,6,7,8-tetrahydroquinoline-6-carboxylic acid (15 mg, 0.052 mmol) in a 2 mL vial, and the mixture stirred at room temperature for 1 h, before a solution of (R)—N-(4-(1-aminoethyl)-5-fluoro-2-methylphenyl)methanesulfonamide hydrochloride (18 mg, 0.063 mmol) in N-methylpyrrolidinone (200 uL) was added. After 18 h the mixture was filtered and purified by reverse-phase HPLC (30-75% MeCN in 10 mM Et2NH/H2O) to afford the amide as a solid (12.3 mg, 46%). 1H NMR (400 MHz, DMSO-d6) δ 9.08 (s, 1H), 8.41 (app dd, J=7.7, 12.0 Hz, 1H), 7.53 (app dd, J=3.3, 8.1 Hz, 1H), 7.35 (d, J=8.1 Hz, 1H), 7.22 (d, J=8.5 Hz, 1H), 7.07 (d, J=11.6 Hz, 1H), 5.09 (app hextet, J=7.3 Hz, 1H), 3.01 (s, 3H), 2.92-2.78 (m, 4H), 2.71-2.61 (m, 1H), 2.26 (s, 3H), 2.06-1.97 (m, 1H), 1.87-1.69 (m, 1H), 1.53 (s, 3H), 1.35 (d, J=7.1 Hz, 3H); m/z=516.3 (M+H)+.

Workup

  1. additionwas added
  2. filtrationAfter 18 h the mixture was filtered
  3. custompurified by reverse-phase HPLC (30-75% MeCN in 10 mM Et2NH/H2O)

Sources & evidence

ORD record
ord-ecf36d0ba65c4dbb83aa4fa2b044b555
Source dataset
uspto-grants-2012_04
Patent number
US08153651B2

Reaction notes

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