Diisopropylethylamine → (5-Chloro-pyridin-2-yl)-{2-[6-(2-ethyl-5-fluoro-4-hydroxy-phenyl)-1H-indazol-3-yl]-4,5,7,8-tetrahydro-1H-imidazo[4,5-d]azepin-6-yl}-methanone

HRID 2038664노트

반응식

HRID 2038664 반응식
[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]([OH:10])=O)=[N:6][CH:7]=1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.Br.Br.Br.[CH2:38]([C:40]1[C:41]([C:48]2[CH:56]=[C:55]3[C:51]([C:52]([C:57]4[NH:66][C:60]5[CH2:61][CH2:62][NH:63][CH2:64][CH2:65][C:59]=5[N:58]=4)=[N:53][NH:54]3)=[CH:50][CH:49]=2)=[CH:42][C:43]([F:47])=[C:44]([OH:46])[CH:45]=1)[CH3:39].CCN(C(C)C)C(C)C.C(=O)([O-])O.[Na+]>CN(C=O)C>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]([N:63]2[CH2:62][CH2:61][C:60]3[N:66]=[C:57]([C:52]4[C:51]5[C:55](=[CH:56][C:48]([C:41]6[CH:42]=[C:43]([F:47])[C:44]([OH:46])=[CH:45][C:40]=6[CH2:38][CH3:39])=[CH:49][CH:50]=5)[NH:54][N:53]=4)[NH:58][C:59]=3[CH2:65][CH2:64]2)=[O:10])=[N:6][CH:7]=1

참가 물질

7

반응물 5

HCID 81531DiisopropylethylamineHCID 516892Sodium BicarbonateHCID 27628725-Chloro-2-picolinic acidHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 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 136263947(5-Chloro-pyridin-2-yl)-{2-[6-(2-ethyl-5-fluoro-4-hydroxy-phenyl)-1H-indazol-3-yl]-4,5,7,8-tetrahydro-1H-imidazo[4,5-d]azepin-6-yl}-methanone수율 48.3%

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

실험 절차

To a solution of 5-chloro-pyridine-2-carboxylic acid (13.2 mg, 85 μmol) in DMF (1 mL) was added HATU (32 mg, 85 μmol) and the resulting reaction mixture was stirred at room temperature for 30 minutes. 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, 50 mg, 80 μmol) and DIPEA (56 μL, 320 μmol) were added and stirring was continued at room temperature for 18 hours. Saturated aqueous sodium hydrogen carbonate solution (5 mL) was added to the reaction mixture. 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 20.5 mg of the title compound.

후처리

  1. customthe resulting reaction mixture
  2. stirringstirring
  3. waitwas continued at room temperature for 18 hours
  4. filtrationThe resulting solid was collected by filtration
  5. washwashed with further saturated aqueous sodium hydrogen carbonate solution
  6. customThe crude material was purified by HPLC Method A

출처 및 근거

ORD 기록
ord-ace0d364f8c94559a38ecc97288fb11b
출처 데이터셋
uspto-grants-2013_11
특허 번호
US08575336B2

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