Diisopropylethylamine → (R)-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 1690786Notes

Reaction equation

HRID 1690786 reaction equation
C(N(CC)C(C)C)(C)C.[F:10][C:11]([F:29])([F:28])[C:12]([C:15]1[CH:24]=[CH:23][C:22]2[CH2:21][C@H:20]([C:25]([OH:27])=O)[CH2:19][CH2:18][C:17]=2[N:16]=1)([CH3:14])[CH3:13].F[P-](F)(F)(F)(F)F.C[N+](C)=C(N(C)C)ON1C2N=CC=CC=2N=N1.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:25]([C@@H:20]1[CH2:19][CH2:18][C:17]2[N:16]=[C:15]([C:12]([CH3:14])([CH3:13])[C:11]([F:29])([F:10])[F:28])[CH:24]=[CH:23][C:22]=2[CH2:21]1)=[O:27])[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 58118619(R)-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-carboxamideYield 60.6%

Reagents, catalysts & solvents 1

HCID 13387N-methyl-2-pyrrolidoneSolvent2×

Procedure

N-methylpyrrolidinone (1.2 mL) and N,N-diisopropylethylamine (87 uL, 0.50 mmol) were added to (R)-2-(1,1,1-trifluoro-2-methylpropan-2-yl)-5,6,7,8-tetrahydroquinoline-6-carboxylic acid (47 mg, 0.16 mmol) and N,N,N′,N′-tetramethyl-O-(7-azabenzotriazol-1-yl)uronium hexafluorophosphate (75 mg, 0.20 mmol) in a 4 mL vial, and the mixture stirred at room temperature for 10 min, before a solution of (R)—N-(4-(1-aminoethyl)-5-fluoro-2-methylphenyl)methanesulfonamide hydrochloride (55 mg, 0.19 mmol) in N-methylpyrrolidinone (0.5 mL) was added. After 30 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 (50 mg, 58%). 1H NMR (400 MHz, DMSO-d6) δ 9.12 (br s, 1H), 8.39 (d, J=8.1 Hz, 1H), 7.53 (d, J=8.1 Hz, 1H), 7.34 (d, J=8.1 Hz, 1H), 7.22 (d, J=8.6 Hz, 1H), 7.06 (d, J=11.7 Hz, 1H), 5.10 (app pentet, J=7.2 Hz, 1H), 3.00 (s, 3H), 2.93-2.76 (m, 4H), 2.68-2.59 (m, 1H), 2.25, (s, 3H), 2.09-2.03 (m, 1H), 1.88-1.76 (m, 1H), 1.54 (s, 3H), 1.35 (d, J=7.0 Hz, 3H); m/z=515.8 (M+H)+.

Workup

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

Sources & evidence

ORD record
ord-c14e6274ce26480fb76681c288b4a0d8
Source dataset
uspto-grants-2012_04
Patent number
US08153651B2

Reaction notes

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