Diisopropylethylamine → Trifluoroacetic acid

HRID 713340Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 713340
[CH3:1][O:2][C@@H:3]([CH3:7])[C:4]([OH:6])=O.CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[OH:41][C:42]([C:44]([F:47])([F:46])[F:45])=[O:43].[F:48][CH:49]([F:77])[CH2:50][NH:51][C:52]1[N:57]=[C:56]2[CH2:58][NH:59][CH2:60][CH2:61][C:55]2=[N:54][C:53]=1[N:62]1[CH2:67][CH2:66][CH:65]([O:68][C:69]2[CH:74]=[CH:73][C:72]([F:75])=[CH:71][C:70]=2[F:76])[CH2:64][CH2:63]1>CN(C=O)C>[F:77][CH:49]([F:48])[CH2:50][NH:51][C:52]1[N:57]=[C:56]2[CH2:58][N:59]([C:4](=[O:6])[C@@H:3]([O:2][CH3:1])[CH3:7])[CH2:60][CH2:61][C:55]2=[N:54][C:53]=1[N:62]1[CH2:63][CH2:64][CH:65]([O:68][C:69]2[CH:74]=[CH:73][C:72]([F:75])=[CH:71][C:70]=2[F:76])[CH2:66][CH2:67]1.[C:42]([OH:43])([C:44]([F:47])([F:46])[F:45])=[O:41]

Komponenten

7

Edukt 4

HCID 81531DiisopropylethylamineHCID 57025662-methoxypropanoic acid, (S)-HCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 131734033N-(2,2-difluoroethyl)-2-(4-(2,4-difluorophenoxy)piperidin-1-yl)-5,6,7,8-tetrahydropyrido[3,4-b]pyrazin-3-amine TFA salt

Produkt 2

HCID 6422Trifluoroacetic acidAusbeute 94 %HCID 118159237(S)-1-(3-(2,2-difluoroethylamino)-2-(4-(2,4-difluorophenoxy)piperidin-1-yl)-7,8-dihydropyrido[3,4-b]pyrazin-6(5H)-yl)-2-methoxypropan-1-one

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6228DimethylformamideLösungsmittel2×

Versuchsvorschrift

A solution of (S)-2-methoxypropanoic acid (2.9 mg, 0.028 mmol), DIPEA (3.9 mg, 0.028 mmol), and HATU (10.6 mg, 0.028 mmol) in DMF (278 μL) was stirred at room temperature for 10 min then treated with N-(2,2-difluoroethyl)-2-(4-(2,4-difluorophenoxyl)piperidin-1-yl)-5,6,7,8-tetrahydropyrido[3,4-b]pyrazin-3-amine TFA salt (15 mg, 0.028 mmol). Stirring was continued overnight. The crude reaction mixture was diluted in DMF, filtered through a hydrophilic PTFE 0.45 μm filter (Millipore® Millex-LCR), and purified via HPLC Method A to give the title compound as a TFA salt (3 mg) as a clear oil. 1H NMR (400 MHz, methanol-d4, mixture of rotamers) δ ppm 1.32 (d, J=6.6 Hz, 1.3H), 1.38 (d, J=6.6 Hz, 1.7H), 1.91-2.04 (m, 2H), 2.09-2.19 (m, 2H), 2.76 (t, J=6.2 Hz, 0.9H), 2.84 (t, J=5.4 Hz, 1.1H), 2.95-3.05 (m, 2H), 3.33 (s, 3H), 3.35-3.43 (m, 2H), 3.78 (td, J=14.6, 4.3 Hz, 2H), 3.83-3.98 (m, 2H), 4.32-4.41 (m, 1H), 4.42-4.49 (m, 1H), 4.56 (m, 1.1H), 4.68 (m, 0.9H), 5.89-6.22 (m, 1H), 6.85-6.91 (m, 1H), 6.98 (ddd, J=11.2, 8.5, 3.0 Hz, 1H), 7.17 (td, J=9.2, 5.6 Hz, 1H); ESI-MS m/z [M+H]+ 512.4.

Aufarbeitung

  1. customThe crude reaction mixture
  2. filtrationfiltered through a hydrophilic PTFE 0.45 μm
  3. filtrationfilter (Millipore® Millex-LCR)
  4. custompurified via HPLC Method A

Quellen und Nachweise

ORD-Eintrag
ord-04ff53b1c47048bead2fadc64c1f8034
Quelldatensatz
uspto-grants-2015_11
Patentnummer
US09181249B2

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