Diisopropylethylamine → Epz015666

HRID 2202074Notizen

Reaktionsgleichung

Cl[C:2]1[N:7]=[CH:6][N:5]=[C:4]([C:8]([NH:10][CH2:11][C@H:12]([OH:24])[CH2:13][N:14]2[CH2:23][CH2:22][C:21]3[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=3)[CH2:15]2)=[O:9])[CH:3]=1.[O:25]1[CH2:28][CH:27]([NH2:29])[CH2:26]1.CCN(C(C)C)C(C)C>CC(O)C>[CH2:15]1[C:16]2[C:21](=[CH:20][CH:19]=[CH:18][CH:17]=2)[CH2:22][CH2:23][N:14]1[CH2:13][C@@H:12]([OH:24])[CH2:11][NH:10][C:8]([C:4]1[CH:3]=[C:2]([NH:29][CH:27]2[CH2:28][O:25][CH2:26]2)[N:7]=[CH:6][N:5]=1)=[O:9]

Komponenten

Reaktionsbedingungen

Temperatur: 110 °C

Versuchsvorschrift

To a solution of (S)-6-chloro-N-(3-(3,4-dihydroisoquinolin-2(1H)-yl)-2-hydroxy propyl)pyrimidine-4-carboxamide (347 mg, 1 mmol) in i-PrOH (5 mL) was added oxetan-3-amine (73.1 mg, 1 mmol) and DIPEA (129 mg, 1 mmol). The resulting mixture was stirred at 110° C. for 16 hours, at which time LCMS showed the completion of the reaction. After evaporation of the solvent, the residue was purified by preparative HPLC to give the target compound (S)—N-(3-(3,4-dihydroisoquinolin-2(1H)-yl)-2-hydroxypropyl)-6-(oxetan-3-ylamino)pyrimidine-4-carboxamide (62.5 mg, yield: 16.3%). 1H NMR (400 MHz, MeOD-d4) δ 8.24 (s, 1H), 7.15-7.05 (m, 4H), 7.02-6.98 (m, 1H), 5.09 (s, 1H), 4.95 (t, J=6.8 Hz, 2H), 4.59 (t, J=6.3 Hz, 2H), 4.10-4.03 (m, 1H), 3.72 (s, 2H), 3.56-3.46 (m, 2H), 2.96-2.91 (m, 2H), 2.87-2.80 (m, 2H), 2.65 (d, J=6.3 Hz, 2H). LCMS (m/z): 384.1 [M+H]+.

Aufarbeitung

customthe completion of the reaction
customAfter evaporation of the solvent
customthe residue was purified by preparative HPLC

Quellen und Nachweise

ORD-Eintrag: ord-d4179ed183064e2fb827adfef61b4a4e
Quelldatensatz: uspto-grants-2016_06
DOI: 10.6084/m9.figshare.5104873.v1
Patentnummer: US09365519B2

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