Acetic Acid → HCID 178425118、化合物

反応式

[NH2:1][C:2]1[CH:3]=[CH:4][N:5]([CH3:27])[C:6]2[C:7]=1[CH:8]=[CH:9][C:10]1[N:19]([C:20]3[CH:25]=[CH:24][C:23]([F:26])=[CH:22][CH:21]=3)[CH2:18][CH:17]=[C:12]3[NH:13][C:14](=[O:16])[C:15]=2[C:11]=13.C(O)(=O)C.C([BH3-])#N.[Na+].[CH3:36][C:37]1[N:42]=[C:41]([CH:43]=O)[CH:40]=[CH:39][CH:38]=1>>[F:26][C:23]1[CH:22]=[CH:21][C:20]([N:19]2[C:10]3=[C:11]4[C:15](=[C:6]5[N:5]([CH3:27])[CH:4]=[CH:3][C:2]([NH:1][CH2:43][C:41]6[CH:40]=[CH:39][CH:38]=[C:37]([CH3:36])[N:42]=6)=[C:7]5[CH:8]=[CH:9]3)[C:14](=[O:16])[NH:13][C:12]4=[CH:17][CH2:18]2)=[CH:25][CH:24]=1

参加物

反応物 4

HCID 176Acetic Acid

HCID 707376-Methyl-2-pyridinecarboxaldehyde

HCID 5003444Sodium cyanoborohydride

HCID 178480427HCID 178480427、化合物

生成物 1

HCID 178425118HCID 178425118、化合物収率 44%

実験手順

A stock solution of Example 23e (0.164 M in N,N-dimethylacetamide, 255 mL, 0.042 mmol), acetic acid (4 M in methanol, 200 mL, 0.84 mmol), sodium cyanoborohydride (0.31 M in methanol, 200 mL, 0.063 mmol) and 6-methylpicolinaldehyde (0.40 M in N,N-dimethylacetamide, 156 mL, 0.063 mmol) were aspirated from their respective source vials, mixed through a perfluoroalkoxy mixing tube (0.2 mm inner diameter), and loaded into an injection loop. The reaction segment was injected into the flow reactor (Hastelloy coil, 0.75 mm inner diameter, 1.8 mL internal volume) set at 50° C., and passed through the reactor at 180 μL per minute (10 minute residence time). Upon exiting the reactor, the reaction mixture was loaded directly into an injection loop and purified by reverse phase HPLC(C8, acetonitrile/water (0.1% ammonium acetate), 5-100%) to give 0.0085 g (44%) of the title compound. 1H NMR (400 MHz, DMSO-d6/D2O) δ 10.85 (s, 1H), 8.41 (d, J=1.83 Hz, 1H), 7.96 (s, 1H), 7.81 (dd, J=8.24, 1.83 Hz, 1H), 7.38 (m, 2H), 7.04 (s, 1H), 6.87 (m, J=9.00, 9.00 Hz, 3H), 6.58 (m, 3H), 4.58 (m, 2H), 4.06 (s, 3H), 3.90 (s, 3H), 3.17 (s, 2H). MS (APCI+) m/z 466.1 (M+H)+.