Diisopropylethylamine → 5-{2-[6-(2-Ethyl-5-fluoro-4-hydroxy-phenyl)-1H-indazol-3-yl]-4,5,7,8-tetrahydro-1H-imidazo[4,5-d]azepine-6-carbonyl}-pyridine-2-carbonitrile

HRID 340022노트

반응식

HRID 340022 반응식
Br.Br.Br.[CH2:4]([C:6]1[C:7]([C:14]2[CH:22]=[C:21]3[C:17]([C:18]([C:23]4[NH:32][C:26]5[CH2:27][CH2:28][NH:29][CH2:30][CH2:31][C:25]=5[N:24]=4)=[N:19][NH:20]3)=[CH:16][CH:15]=2)=[CH:8][C:9]([F:13])=[C:10]([OH:12])[CH:11]=1)[CH3:5].[C:33]([C:35]1[CH:43]=[CH:42][C:38]([C:39](Cl)=[O:40])=[CH:37][N:36]=1)#[N:34].CCN(C(C)C)C(C)C.C(=O)([O-])O.[Na+]>CN(C=O)C>[CH2:4]([C:6]1[CH:11]=[C:10]([OH:12])[C:9]([F:13])=[CH:8][C:7]=1[C:14]1[CH:22]=[C:21]2[C:17]([C:18]([C:23]3[NH:32][C:26]4[CH2:27][CH2:28][N:29]([C:39]([C:38]5[CH:42]=[CH:43][C:35]([C:33]#[N:34])=[N:36][CH:37]=5)=[O:40])[CH2:30][CH2:31][C:25]=4[N:24]=3)=[N:19][NH:20]2)=[CH:16][CH:15]=1)[CH3:5]

참가 물질

6

반응물 4

HCID 81531DiisopropylethylamineHCID 516892Sodium BicarbonateHCID 235126576-Cyanopyridine-3-carbonyl chlorideHCID 1363339625-Ethyl-2-fluoro-4-[3-(1,4,5,6,7,8-hexahydro-imidazo[4,5-d]azepin-2-yl)-1H-indazol-6-yl]-phenol trihydrobromide salt

생성물 1

HCID 1362639685-{2-[6-(2-Ethyl-5-fluoro-4-hydroxy-phenyl)-1H-indazol-3-yl]-4,5,7,8-tetrahydro-1H-imidazo[4,5-d]azepine-6-carbonyl}-pyridine-2-carbonitrile수율 44.9%

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

실험 절차

To a solution of 5-ethyl-2-fluoro-4-[3-(1,4,5,6,7,8-hexahydro-imidazo[4,5-d]azepin-2-yl)-1H-indazol-6-yl]-phenol trihydrobromide salt (Preparation 32, 28 mg, 44 μmol) in DMF (1 mL), was added 6-cyano-nicotinoyl chloride (Preparation 46, 20.9 mg, 141 μmol), and DIPEA (31 μL, 176 μmol). The reaction mixture was stirred at room temperature for 18 hours and then saturated aqueous sodium hydrogen carbonate solution (5 mL) was added. The resulting solid was collected by filtration and washed with further saturated aqueous sodium hydrogen carbonate solution. The crude material was purified by HPLC Method A to afford 10.3 mg of the title compound.

후처리

  1. filtrationThe resulting solid was collected by filtration
  2. washwashed with further saturated aqueous sodium hydrogen carbonate solution
  3. customThe crude material was purified by HPLC Method A

출처 및 근거

ORD 기록
ord-22bd1903cac44cba9cab836a7611d384
출처 데이터셋
uspto-grants-2014_11
특허 번호
US08895544B2

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