Acetonitrile → HCID 67347093, Verbindung

Reaktionsgleichung

N[C:2]1[N:7]=[CH:6][C:5]([O:8][C:9]2[CH:14]=[CH:13][N:12]=[C:11]3[CH:15]=[C:16]([C:18]4[CH:27]=[CH:26][C:21]([C:22]([NH:24][CH3:25])=[O:23])=[CH:20][CH:19]=4)[S:17][C:10]=23)=[CH:4][CH:3]=1.[F:28][C:29]1[CH:34]=[CH:33][C:32]([NH:35][C:36]([C:38]2([C:41](F)=[O:42])[CH2:40][CH2:39]2)=[O:37])=[CH:31][CH:30]=1.CC#[N:46]>>[F:28][C:29]1[CH:34]=[CH:33][C:32]([N:35]([C:2]2[CH:3]=[CH:4][C:5]([O:8][C:9]3[CH:14]=[CH:13][N:12]=[C:11]4[CH:15]=[C:16]([C:18]5[CH:27]=[CH:26][C:21]([C:22](=[O:23])[NH:24][CH3:25])=[CH:20][CH:19]=5)[S:17][C:10]=34)=[CH:6][N:7]=2)[C:36]([C:38]2([C:41]([NH2:46])=[O:42])[CH2:40][CH2:39]2)=[O:37])=[CH:31][CH:30]=1

Komponenten

Edukt 3

HCID 6342Acetonitrile

HCID 67347606HCID 67347606, Verbindung

HCID 866146491-((4-Fluorophenyl)carbamoyl)cyclopropanecarbonyl fluoride

Produkt 1

HCID 67347093HCID 67347093, VerbindungAusbeute 11 %

Versuchsvorschrift

A stirred mixture of 4-(7-(6-aminopyridin-3-yloxy)thieno[3,2-b]pyridin-2-yl)-N-methyl-benzamide (11 mg, 0.029 mmol) and 1-((4-fluorophenyl)carbamoyl)cyclopropanecarbonyl fluoride (9.9 mg, 0.044 mmol), in CH3CN (0.5 mL) was heated at 100° C. for 3 hours. After cooling to room temperature, the mixture was partitioned between EtOAc (5 mL) and 1:1 saturated aqueous NaHCO3/water (5 mL). The phases were separated, and the aqueous phase was re-extracted with EtOAc (2×5 mL). The combined organic phases were washed with brine (5 mL), dried (Na2SO4), filtered, and concentrated. The crude was purified by preparative TLC (0.5 mm thickness, Rf=0.30), eluting with 10% MeOH/CHCl3. The product was obtained as a beige solid (2 mg, 11%). HPLC: 100% purity (220 nm); LRMS (ESI+): 94% purity, 220 nm, m/z 582 (M+1) detected; 1H NMR (400 MHz, CDCl3) δ 9.59 (s, 1H), 9.01 (s, 1H), 8.53 (d, J=5 Hz, 1H), 8.29 (m, 2H), 7.85 (m, 5H), 7.55 (m, 3H), 7.04 (t, J=9 Hz, 2H), 6.56 (d, J=5 Hz, 1H), 6.19 (m, 1H), 3.06 (d, J=5 Hz, 3H), 1.82 (m, 2H), 1.68 (m, 2H).