D-Lactic Acid → HCID 67421921, Verbindung

HRID 515242

Reaktionsgleichung

Reaktionsgleichung von HRID 515242
[F:1][C:2]1([F:32])[CH2:4][CH:3]1[CH2:5][N:6]1[C:14]2[C:9](=[N:10][C:11]([C:15]3[CH:20]=[C:19]([CH2:21][N:22]4[CH2:27][CH2:26][NH:25][CH2:24][CH2:23]4)[CH:18]=[CH:17][C:16]=3[CH3:28])=[CH:12][CH:13]=2)[N:8]([CH3:29])[S:7]1(=[O:31])=[O:30].CCN(C(C)C)C(C)C.[C:42](O)(=[O:46])[C@@H:43]([CH3:45])[OH:44].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN1C(=O)CCC1.CCOC(C)=O>[F:32][C:2]1([F:1])[CH2:4][CH:3]1[CH2:5][N:6]1[C:14]2[C:9](=[N:10][C:11]([C:15]3[CH:20]=[C:19]([CH:18]=[CH:17][C:16]=3[CH3:28])[CH2:21][N:22]3[CH2:27][CH2:26][N:25]([C:42](=[O:46])[C@H:43]([OH:44])[CH3:45])[CH2:24][CH2:23]3)=[CH:12][CH:13]=2)[N:8]([CH3:29])[S:7]1(=[O:31])=[O:30]

Komponenten

7

Edukt 4

HCID 61503D-Lactic AcidHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 67410748HCID 67410748, Verbindung

Produkt 1

HCID 67421921HCID 67421921, Verbindung

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 8857Ethyl AcetateLösungsmittelHCID 13387N-methyl-2-pyrrolidoneLösungsmittel

Versuchsvorschrift

1-[(2,2-difluorocyclopropyl)methyl]-3-methyl-5-[2-methyl-5-(piperazin-1-ylmethyl)phenyl]-1,3-dihydro[1,2,5]thiadiazolo[3,4-b]pyridine 2,2-dioxide (43-2) (2.3 g, 5.0 mmol, 1.0 eq) was dissolved in NMP (25 mL) and DIPEA (2.6 mL, 14.9 mmol, 3.0 eq), D-lactic acid (536 mg, 6.0 mmol, 1.2 eq) and HATU (2.8 g, 7.4 mmol, 1.5 eq) were added. The reaction mixture stirred at ambient temperature for 5 minutes and was then diluted with EtOAc (200 mL), washed with sodium bicarbonate (4×30 mL) and brine (30 mL), dried over MgSO4, filtered and concentrated. The crude residue was purified by flash chromatography (120 g SiO2, 0-40% IPA in DCM) to afford (2R)-1-[4-(3-{1-[(2,2-difluorocyclopropyl)methyl]-3-methyl-2,2-dioxido-1,3-dihydro[1,2,5]thiadiazolo[3,4-b]pyridin-5-yl}-4-methylbenzyl)piperazin-1-yl]-2-hydroxypropan-1-one (43-3) as a white solid. 1H NMR (400 MHz, CD3OD): δ 7.37 (d, J=8.4 Hz, 1 H); 7.35 (s, 1 H); 7.26 (s, 2 H); 7.08 (d, J=8.4 Hz, 1 H); 4.54 (q, J=6.8 Hz, 1 H); 3.98 (d, J=6.8 Hz, 2 H); 3.64 (m, 4 H); 3.57 (s, 2 H); 3.38 (s, 3 H); 2.49 (m, 4 H); 2.36 (s, 3 H); 2.21 (m, 1 H); 1.67 (m, 1 H); 1.43 (m, 1 H); 1.18 (d, J=6.8 Hz, 3 H). HRMS m/z (M+H) 536.2136 found, 536.2138 required.

Aufarbeitung

  1. washwashed with sodium bicarbonate (4×30 mL) and brine (30 mL)
  2. dry with materialdried over MgSO4
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customThe crude residue was purified by flash chromatography (120 g SiO2, 0-40% IPA in DCM)

Quellen und Nachweise

ORD-Eintrag
ord-e472e50948054f7494de4ac652e07f1b
Quelldatensatz
uspto-grants-2015_08
Patentnummer
US09108937B2

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