Isopropanol → HCID 56644307、化合物

反応式

Cl.Cl[C:3]1[N:8]=[C:7]([NH:9][CH:10]2[CH2:15][C:14]([CH3:17])([CH3:16])[NH:13][C:12]([CH3:19])([CH3:18])[CH2:11]2)[C:6]([F:20])=[CH:5][N:4]=1.[CH:21]1([C:24]2[C:29]([N:30]3[C:34]([CH:35]([CH3:37])[CH3:36])=[N:33][N:32]=[N:31]3)=[CH:28][C:27]([NH2:38])=[C:26]([F:39])[CH:25]=2)[CH2:23][CH2:22]1.[CH:40]([OH:43])(C)C>>[NH3:4].[CH3:40][OH:43].[CH:21]1([C:24]2[C:29]([N:30]3[C:34]([CH:35]([CH3:37])[CH3:36])=[N:33][N:32]=[N:31]3)=[CH:28][C:27]([NH:38][C:3]3[N:8]=[C:7]([NH:9][CH:10]4[CH2:15][C:14]([CH3:17])([CH3:16])[NH:13][C:12]([CH3:19])([CH3:18])[CH2:11]4)[C:6]([F:20])=[CH:5][N:4]=3)=[C:26]([F:39])[CH:25]=2)[CH2:22][CH2:23]1

参加物

反応物 3

HCID 3776Isopropanol

HCID 58065813HCID 58065813、化合物

HCID 86653878HCID 86653878、化合物

生成物 2

HCID 21705897Ammonia methanol収率 1%

HCID 56644307HCID 56644307、化合物収率 52%

反応条件

温度: 70 °C

実験手順

A mixture of 2-chloro-5-fluoro-N-(2,2,6,6-tetramethylpiperidin-4-yl)pyrimidin-4-amine hydrochloride (300 mg, 0.928 mmol, 1 equiv), 4-cyclopropyl-2-fluoro-5-(5-isopropyl-1H-tetrazol-1-yl)benzenamine (291 mg, 1.11 mmol, 1.2 equiv), and PTSA monohydrate (191 mg, 0.742 mmol, 0.8 equiv) in isopropyl alcohol (10 mL) were heated to 70° C. for 7 days. After cooling to ambient temperature, the crude reaction mixture was concentrated to dryness and taken in water, EtOAc, and 1N NaOH. The layers were separated. The organic layer was washed with 1N NaOH 2×, dried over Na2SO4, filtered, and concentrated to dryness. The crude product was purified by flash chromatography and eluted with DCM:2M NH3/MeOH=100:0 to 96:4 using 1% 2M NH3/MeOH increments to give compound N2-(4-cyclopropyl-2-fluoro-5-(5-isopropyl-1H-tetrazol-1-yl)phenyl)-5-fluoro-N4-(2,2,6,6-tetramethylpiperidin-4-yl)pyrimidine-2,4-diamine (245 mg, 52%) as a solid.