4-Methylmorpholine → 3-hydroxy-N-((3S,7S,8R,9S)-8-isobutoxy-9-methyl-7-(4-methylbenzyl)-2-oxo-1,5-dioxonan-3-yl)-4-methoxypicolinamide

HRID 58956

Reaktionsgleichung

Reaktionsgleichung von HRID 58956
[OH:1][C:2]1[C:3]([C:10]([OH:12])=O)=[N:4][CH:5]=[CH:6][C:7]=1[O:8][CH3:9].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CN1CCOCC1.[NH2:44][C@H:45]1[CH2:53][O:52][CH2:51][C@H:50]([CH2:54][C:55]2[CH:60]=[CH:59][C:58]([CH3:61])=[CH:57][CH:56]=2)[C@@H:49]([O:62][CH2:63][CH:64]([CH3:66])[CH3:65])[C@H:48]([CH3:67])[O:47][C:46]1=[O:68]>C(Cl)Cl>[OH:1][C:2]1[C:3]([C:10]([NH:44][C@H:45]2[CH2:53][O:52][CH2:51][C@H:50]([CH2:54][C:55]3[CH:60]=[CH:59][C:58]([CH3:61])=[CH:57][CH:56]=3)[C@@H:49]([O:62][CH2:63][CH:64]([CH3:65])[CH3:66])[C@H:48]([CH3:67])[O:47][C:46]2=[O:68])=[O:12])=[N:4][CH:5]=[CH:6][C:7]=1[O:8][CH3:9]

Komponenten

6

Edukt 4

HCID 79724-MethylmorpholineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 110411213-Hydroxy-4-methoxypyridine-2-carboxylic acidHCID 117974554(3S,7S,8R,9S)-3-amino-8-isobutoxy-9-methyl-7-(4-methylbenzyl)-1,5-dioxonan-2-one

Produkt 1

HCID 1179741893-hydroxy-N-((3S,7S,8R,9S)-8-isobutoxy-9-methyl-7-(4-methylbenzyl)-2-oxo-1,5-dioxonan-3-yl)-4-methoxypicolinamideAusbeute 77 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6344DichloromethaneLösungsmittel

Versuchsvorschrift

To a mixture of 3-hydroxy-4-methoxypicolinic acid (0.198 g, 1.17 mmol), HATU (0.47 g, 1.25 mmol), and N-methylmorpholine (0.47 g, 4.7 mmol) in CH2Cl2 (9 mL) was added (3S,7S,8R,9S)-3-amino-8-isobutoxy-9-methyl-7-(4-methylbenzyl)-1,5-dioxonan-2-one (272 mg, 0.78 mmol), and the tan mixture was stirred at room temperature for 7 h. The resulting homogeneous solution was adsorbed to Celite® and purified by flash chromatography (SiO2, 0→30% acetone/hexanes) to give 3-hydroxy-N-((3S,7S,8R,9S)-8-isobutoxy-9-methyl-7-(4-methylbenzyl)-2-oxo-1,5-dioxonan-3-yl)-4-methoxypicolinamide (0.30 g, 77%) as a white foam: 1H NMR (400 MHz, CDCl3) δ 11.95 (s, 1H), 8.54 (d, J=8.3 Hz, 1H), 7.97 (d, J=5.2 Hz, 1H), 7.09 (d, J=2.1 Hz, 4H), 6.85 (d, J=5.2 Hz, 1H), 5.01 (m, 2H), 4.02 (dd, J=11.7, 7.3 Hz, 1H), 3.92 (s, 3H), 3.46 (m, 4H), 3.34 (dd, J=8.3, 6.5 Hz, 1H), 3.13 (m, 2H), 2.31 (s, 4H), 1.93 (m, 2H), 1.50 (d, J=6.4 Hz, 3H), 0.96 (d, J=6.7 Hz, 6H); 13C NMR (101 MHz, CDCl3) δ 171.15, 168.90, 155.31, 148.71, 140.62, 136.76, 135.58, 130.20, 129.15, 129.05, 109.56, 84.61, 79.28, 75.92, 72.53, 72.16, 56.08, 51.53, 47.47, 34.60, 29.20, 21.03, 19.50, 18.83; HRMS-ESI (m/z) [M+H]+ calcd for C27H36N2O7, 500.2523. found, 500.2529.

Aufarbeitung

  1. custompurified by flash chromatography (SiO2, 0→30% acetone/hexanes)

Quellen und Nachweise

ORD-Eintrag
ord-a4977fdf683a456a8f6673a0f7ca3db5
Quelldatensatz
uspto-grants-2016_09
Patentnummer
US09439422B2

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