Sodium Bicarbonate → HCID 178521182, 화합물

HRID 1601316노트

반응식

HRID 1601316 반응식
[F:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([CH:11]3[CH2:16][CH2:15][NH:14][CH2:13][CH2:12]3)=[N:7][NH:8]2)=[CH:4][CH:3]=1.Br[CH2:18][C:19]([N:21]1[CH2:30][CH2:29][C:28]2[C:23](=[CH:24][CH:25]=[CH:26][CH:27]=2)[CH2:22]1)=[O:20].C(=O)(O)[O-].[Na+]>CC#N>[CH2:22]1[C:23]2[C:28](=[CH:27][CH:26]=[CH:25][CH:24]=2)[CH2:29][CH2:30][N:21]1[C:19](=[O:20])[CH2:18][N:14]1[CH2:15][CH2:16][CH:11]([C:6]2[C:5]3[C:9](=[CH:10][C:2]([F:1])=[CH:3][CH:4]=3)[NH:8][N:7]=2)[CH2:12][CH2:13]1

참가 물질

5

반응물 3

HCID 516892Sodium BicarbonateHCID 184672392-Bromo-1-(1,2,3,4-tetrahydroisoquinolin-2-yl)ethan-1-oneHCID 178505426HCID 178505426, 화합물

생성물 1

HCID 178521182HCID 178521182, 화합물수율 55.3%

시약·촉매·용매 1

HCID 6342Acetonitrile용매

실험 절차

To a solution of 4-(6-fluoro-1H-indazol-3-yl)piperidine (4.8 g, 18.9 mmol) in CH3CN (200 ml) was added 2-bromo-1-(1,2,3,4-tetrahydroisoquinolin-2-yl)ethanone (4.8 g, 18.9 mmol) and sodium bicarbonate (1.9 g, 22.7 mmol) at room temperature. The reaction mixture was warmed to reflux (4 hours), cooled to room temperature and filtered through a pad of celite. The solids were washed with DCM and the combined filtrates were concentrated. The remaining residue was purified via preparative HPLC (silica gel, 5-10% MeOH/DCM) to give 4.1 g of 1-(1,2,3,4-tetrahydroisoquinolin-2-yl)-2-[4-(6-fluoro-1H-indazol-3-yl)-1-piperidinyl]ethanone which was used without further purification. To a suspension of the latter (3.7 g, 9.4 mmol) in THF (100 ml) was added (dropwise) lithium aluminum hydride (11.3 ml of 1.0 M solution in THF, 11.3 mmol) at room temperature, under nitrogen. The reaction mixture was warmed to reflux (5 hours), cooled to room temperature and carefully quenched with water (10 ml). The precipitated salts were removed via filtration and washed with 1:1 EtOAc/DCM. The combined filtrates were concentrated and the remaining oil was purified via flash column chromatography (silica gel, 10% MeOH/DCM) to give 2.2 g of the product. The dimaleate salt was prepared in methanol (30 ml) with maleic acid (3.0 eq.), m.p. 185-187° C.

후처리

  1. temperatureThe reaction mixture was warmed
  2. temperatureto reflux (4 hours)
  3. filtrationfiltered through a pad of celite
  4. washThe solids were washed with DCM
  5. concentrationthe combined filtrates were concentrated
  6. customThe remaining residue was purified via preparative HPLC (silica gel, 5-10% MeOH/DCM)

출처 및 근거

ORD 기록
ord-cc15ec499f334d7b9c5c058caa12f7a2
출처 데이터셋
uspto-grants-1999_11
특허 번호
US05977113

반응 노트

불러오는 중…