1,3-Isobenzofurandione, 5-fluoro- → HCID 178515089, 화합물

HRID 55695

반응식

HRID 55695 반응식
[F:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([CH:11]3[CH2:16][CH2:15][N:14]([CH2:17][CH2:18][NH2:19])[CH2:13][CH2:12]3)=[N:7][NH:8]2)=[CH:4][CH:3]=1.[F:20][C:21]1[CH:22]=[C:23]2[C:28](=O)[O:27][C:25](=[O:26])[C:24]2=[CH:30][CH:31]=1.C(Cl)Cl.CO>CN(C=O)C>[F:20][C:21]1[CH:22]=[C:23]2[C:28](=[O:27])[N:19]([CH2:18][CH2:17][N:14]3[CH2:13][CH2:12][CH:11]([C:6]4[C:5]5[C:9](=[CH:10][C:2]([F:1])=[CH:3][CH:4]=5)[NH:8][N:7]=4)[CH2:16][CH2:15]3)[C:25](=[O:26])[C:24]2=[CH:30][CH:31]=1

참가 물질

5

반응물 3

HCID 675721,3-Isobenzofurandione, 5-fluoro-HCID 21226129Dichloromethane methanolHCID 178511315HCID 178511315, 화합물

생성물 1

HCID 178515089HCID 178515089, 화합물수율 37.8%

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

실험 절차

To a solution consisting of 2-[4-(6-fluoro-1H-indazol-3-yl)-1-piperidinyl]ethylamine (6.1 g, 23.2 mmol) in DMF (230 ml) was added 4-fluorophthalic anhydride (4.2 g, 25.5 mmol) at room temperature, under nitrogen. The reaction mixture was warmed to 80 C. for 2.5 hours at which time it was allowed to cool to room temperature. The DMF was removed under reduced pressure (<0.5 mmHg, 55 C.) to give a brown oil which was dissolved into DCM/MeOH. Purification via flash column chromatography (silica gel, 2% MeOH/DCM) afforded 3.6 g of 4-fluoro-N-[2-[4-(6-fluoro-1H-indazol-3-yl)-1-piperidinyl]ethyl]phthalimide. To a solution of the latter compound (3.6 g 8.8 mmol) in anhydrous THF (100 ml) was added LAH (18.4 ml of a 1.0M solution in THF, 18.4 mmol) at room temperature, under nitrogen. The reaction mixture was warmed to reflux for 4 hours. Upon cooling to room temperature, the reaction was quenched with water (1.5 ml, dropwise). The precipitated salts were removed via filtration and washed with DCM. The combined filtrates were concentrated to give a solid which was purified via flash column chromatography (silica gel, 0-8% MeOH/DCM). The product containing fractions were concentrated to give 2.4 g product as an off-white solid. The dimaleate salt was prepared in methanol using 2.4 eq. of maleic acid. The white precipitate was collected via filtration and washed with methanol, m.p. 186°-188° C.

후처리

  1. temperatureThe reaction mixture was warmed to 80 C
  2. customThe DMF was removed under reduced pressure (<0.5 mmHg, 55 C.)
  3. customto give a brown oil which
  4. customPurification via flash column chromatography (silica gel, 2% MeOH/DCM)

출처 및 근거

ORD 기록
ord-df9ea26c86ec42ee8ea5014d1e86fb3c
출처 데이터셋
uspto-grants-1997_04
특허 번호
US05624927

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