Triethylamine → 1-[(4S)-7-(3,5-Dimethylisoxazol-4-yl)-4-pyridin-2-yl-4,5-dihydroimidazo[1,5,4-de][1,4]benzoxazin-2-yl]-3-methylpyrrolidin-3-ol

HRID 589121

Reaktionsgleichung

C(N(CC)CC)C.Cl.[CH3:9][C:10]1([OH:15])[CH2:14][CH2:13][NH:12][CH2:11]1.Cl[C:17]1[N:25]2[C@@H:26]([C:29]3[CH:34]=[CH:33][CH:32]=[CH:31][N:30]=3)[CH2:27][O:28][C:23]3=[C:24]2[C:19](=[CH:20][CH:21]=[C:22]3[C:35]2[C:36]([CH3:41])=[N:37][O:38][C:39]=2[CH3:40])[N:18]=1>CN1CCCC1=O.CO>[CH3:41][C:36]1[C:35]([C:22]2[C:23]3[O:28][CH2:27][C@H:26]([C:29]4[CH:34]=[CH:33][CH:32]=[CH:31][N:30]=4)[N:25]4[C:17]([N:12]5[CH2:13][CH2:14][C:10]([CH3:9])([OH:15])[CH2:11]5)=[N:18][C:19]([C:24]=34)=[CH:20][CH:21]=2)=[C:39]([CH3:40])[O:38][N:37]=1

Komponenten

Reaktionsbedingungen

Temperatur: 150 °C

Versuchsvorschrift

Triethylamine (0.76 mL, 5.5 mmol) and 3-methylpyrrolidin-3-ol hydrochloride (563 mg, 4.09 mmol) were added to (4S)-2-chloro-7-(3,5-dimethylisoxazol-4-yl)-4-pyridin-2-yl-4,5-dihydroimidazo[1,5,4-de][1,4]benzoxazine (100 mg, 0.27 mmol) in N-methylpyrrolidinone (3 mL) and the resulting mixture was heated in a microwave at 150° C. for 20 min. The mixture was then diluted with methanol and purified by preparative LCMS at pH 2 buffer followed by preparative LCMC at pH 10 buffer to give the title compound as a mixture of diastereomers (47.1 mg, 40%). LCMS calc. for C24H26N5O3 (M+H)+: m/z=432.2. found: 432.2. The isomers were separated by prep chiral column chromatography: Column: phenomenex Lux Cellulose C-2 5 μm, 21, 2×250 mm, Mobile phase: 20% EtOH/Hexanes, gradient condition: isocratic at 18 mL/min, run time: 30 min, peak time: 23.0 and 25.7 min.

Aufarbeitung

custompurified by preparative LCMS at pH 2

Quellen und Nachweise

ORD-Eintrag: ord-d51f771ca34949288f8dcb500f73862b
Quelldatensatz: uspto-grants-2016_01
DOI: 10.6084/m9.figshare.5104873.v1
Patentnummer: US09227985B2

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