Diisopropylethylamine → N-((R)-1-(1H-indazol-5-yl)ethyl)-2-(1,1,1-trifluoro-2-methylpropan-2-yl)-5,6,7,8-tetrahydroquinoline-6-carboxamide

HRID 1697469Notes

Reaction equation

HRID 1697469 reaction equation
Cl.Cl.[NH:3]1[C:11]2[C:6](=[CH:7][C:8]([C@H:12]([NH2:14])[CH3:13])=[CH:9][CH:10]=2)[CH:5]=[N:4]1.[F:15][C:16]([F:34])([F:33])[C:17]([C:20]1[CH:29]=[CH:28][C:27]2[CH2:26][C@H:25]([C:30](O)=[O:31])[CH2:24][CH2:23][C:22]=2[N:21]=1)([CH3:19])[CH3:18].C(N(CC)C(C)C)(C)C.F[P-](F)(F)(F)(F)F.C[N+](C)=C(N(C)C)ON1C2N=CC=CC=2N=N1>CN1C(=O)CCC1>[NH:3]1[C:11]2[C:6](=[CH:7][C:8]([C@H:12]([NH:14][C:30]([CH:25]3[CH2:24][CH2:23][C:22]4[N:21]=[C:20]([C:17]([CH3:19])([CH3:18])[C:16]([F:34])([F:33])[F:15])[CH:29]=[CH:28][C:27]=4[CH2:26]3)=[O:31])[CH3:13])=[CH:9][CH:10]=2)[CH:5]=[N:4]1

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 66944333(R)-1-(1H-indazol-5-yl)ethanamine dihydrochloride

Product 1

HCID 67276550N-((R)-1-(1H-indazol-5-yl)ethyl)-2-(1,1,1-trifluoro-2-methylpropan-2-yl)-5,6,7,8-tetrahydroquinoline-6-carboxamideYield 78.6%

Reagents, catalysts & solvents 1

HCID 13387N-methyl-2-pyrrolidoneSolvent3×

Procedure

A 2 mL vial was charged sequentially with a solution of (R)-1-(1H-indazol-5-yl)ethanamine dihydrochloride (34 mg, 0.15 mmol) in NMP (0.2 mL, 2 mmol), a solution of (R)-2-(1,1,1-trifluoro-2-methylpropan-2-yl)-5,6,7,8-tetrahydroquinoline-6-carboxylic acid (38 mg, 0.13 mmol) and N,N-diisopropylethylamine (93 μL, 0.53 mmol) in NMP (0.1 mL). A solution of N,N,N′,N′-tetramethyl-O-(7-azabenzotriazol-1-yl)uronium hexafluorophosphate (61 mg, 0.16 mmol) in NMP (0.3 mL) was added to the resulting mixture and the solution stirred at room temperature. After 30 min the mixture was filtered and purified by reverse-phase HPLC (20-75% MeCN in 10 mM Et2NH/H2O) to afford the amide as a solid (44 mg, 76%). 1H NMR (400 MHz, DMSO-d6) δ 12.98 (br s, 1H), 8.38 (d, J=8.1 Hz, 1H), 8.04 (d, J=0.4 Hz, 1H), 7.66 (s, 1H), 7.50 (t, J=8.1 Hz, 1H), 7.34 (d, J=8.1 Hz, 1H), 5.06 (app pentet, J=7.3 Hz, 1H), 2.94-2.76 (m, 4H), 2.68-2.57 (m, 1H), 2.11-2.03 (m, 1H), 1.90-1.78 (m, 1H), 1.54 (s, 6H), 1.43 (d, J=7.0 Hz, 3H); m/z=431.3 (M+1)+.

Workup

  1. filtrationAfter 30 min the mixture was filtered
  2. custompurified by reverse-phase HPLC (20-75% MeCN in 10 mM Et2NH/H2O)

Sources & evidence

ORD record
ord-f80b00e265524703b59bed37e866787e
Source dataset
uspto-grants-2012_04
Patent number
US08163901B2

Reaction notes

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