Isopropanol → HCID 56644307, 화합물

반응식

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

참가 물질

반응물 3

HCID 3776Isopropanol

HCID 58065813HCID 58065813, 화합물

HCID 86653878HCID 86653878, 화합물

생성물 2

HCID 21705897Ammonia methanol수율 1%

HCID 56644307HCID 56644307, 화합물수율 52%

반응 조건

온도: 70 °C

실험 절차

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.