Diisopropylethylamine → (S)-N-((R)-1-(6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazin-3-yl)ethyl)-2-(1,1,1-trifluoro-2-methylpropan-2-yl)-5,6,7,8-tetrahydroquinoline-6-carboxamide

HRID 1697476Notes

Reaction equation

HRID 1697476 reaction equation
Cl.Cl.[N:3]1[N:11]2[C:6]([O:7][CH2:8][CH2:9][CH2:10]2)=[C:5]([C@H:12]([NH2:14])[CH3:13])[CH: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>CN1CCCC1=O>[N:3]1[N:11]2[C:6]([O:7][CH2:8][CH2:9][CH2:10]2)=[C:5]([C@H:12]([NH:14][C:30]([C@H:25]2[CH2:24][CH2:23][C:22]3[N:21]=[C:20]([C:17]([CH3:19])([CH3:18])[C:16]([F:34])([F:33])[F:15])[CH:29]=[CH:28][C:27]=3[CH2:26]2)=[O:31])[CH3:13])[CH: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 58118635(S)-2-(1,1,1-trifluoro-2-methylpropan-2-yl)-5,6,7,8-tetrahydroquinoline-6-carboxylic acidHCID 66943944(R)-1-(6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazin-3-yl)ethanamine dihydrochloride

Product 1

HCID 58125477(S)-N-((R)-1-(6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazin-3-yl)ethyl)-2-(1,1,1-trifluoro-2-methylpropan-2-yl)-5,6,7,8-tetrahydroquinoline-6-carboxamideYield 54.6%

Reagents, catalysts & solvents 1

HCID 13387N-methyl-2-pyrrolidoneSolvent2×

Procedure

A 2 mL vial was charged with (R)-1-(6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazin-3-yl)ethanamine dihydrochloride (35 mg, 0.15 mmol), (S)-2-(1,1,1-trifluoro-2-methylpropan-2-yl)-5,6,7,8-tetrahydroquinoline-6-carboxylic acid (38 mg, 0.13 mmol), N-methylpyrrolidinone (200 μL) and N,N-diisopropylethylamine (93 μL, 0.53 mmol). A solution of N,N,N′,N′-tetramethyl-O-(7-azabenzotriazol-1-yl)uronium hexafluorophosphate (61 mg, 0.16 mmol) in N-methylpyrrolidinone (300 μL) was added and the resulting mixture was stirred at room temperature for 2 hours. The mixture was filtered and purified by reverse-phase HPLC (20-75% MeCN in 10 mM Et2NH/H2O) to afford the product as a foam (31.0 mg, 53%). 1H NMR (400 MHz, DMSO-d6) δ 8.04 (d, J=7.9 Hz, 1H), 7.53 (d, J=8.1 Hz, 1H), 7.35 (d, J=8.1 Hz, 1H), 7.20 (s, 1H), 4.78 (app pentet, J=7.3 Hz, 1H), 4.27 (app t, J=5.2 Hz, 2H), 4.04 (t, J=6.2 Hz, 2H), 2.93-2.73 (m, 4H), 2.61-2.52 (m, 1H), 2.19-2.10 (m, 2H), 2.03-1.94 (m, 1H), 1.85-1.72 (m, 1H), 1.54 (s, 6H), 1.29 (d, J=6.9 Hz, 3H); m/z=437.4 (M+1)+.

Workup

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

Sources & evidence

ORD record
ord-35c6d29630a54174bc513dd793ae755d
Source dataset
uspto-grants-2012_04
Patent number
US08163901B2

Reaction notes

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