Oxalyl chloride → N-(5-(3,5-Difluorobenzoyl)-1-trityl-1H-indazol-3-yl)-4-(4-methylpiperazin-1-yl)-2-nitrobenzamide

HRID 571893노트

반응식

HRID 571893 반응식
Cl.[CH3:2][N:3]1[CH2:8][CH2:7][N:6]([C:9]2[CH:17]=[CH:16][C:12]([C:13]([OH:15])=O)=[C:11]([N+:18]([O-:20])=[O:19])[CH:10]=2)[CH2:5][CH2:4]1.C(Cl)(=O)C(Cl)=O.[NH2:27][C:28]1[C:36]2[C:31](=[CH:32][CH:33]=[C:34]([C:37]([C:39]3[CH:44]=[C:43]([F:45])[CH:42]=[C:41]([F:46])[CH:40]=3)=[O:38])[CH:35]=2)[N:30]([C:47]([C:60]2[CH:65]=[CH:64][CH:63]=[CH:62][CH:61]=2)([C:54]2[CH:59]=[CH:58][CH:57]=[CH:56][CH:55]=2)[C:48]2[CH:53]=[CH:52][CH:51]=[CH:50][CH:49]=2)[N:29]=1.C(N(CC)C(C)C)(C)C>O1CCCC1.CN(C)C=O>[F:46][C:41]1[CH:40]=[C:39]([CH:44]=[C:43]([F:45])[CH:42]=1)[C:37]([C:34]1[CH:35]=[C:36]2[C:31](=[CH:32][CH:33]=1)[N:30]([C:47]([C:60]1[CH:61]=[CH:62][CH:63]=[CH:64][CH:65]=1)([C:48]1[CH:53]=[CH:52][CH:51]=[CH:50][CH:49]=1)[C:54]1[CH:55]=[CH:56][CH:57]=[CH:58][CH:59]=1)[N:29]=[C:28]2[NH:27][C:13](=[O:15])[C:12]1[CH:16]=[CH:17][C:9]([N:6]2[CH2:5][CH2:4][N:3]([CH3:2])[CH2:8][CH2:7]2)=[CH:10][C:11]=1[N+:18]([O-:20])=[O:19])=[O:38]

참가 물질

7

반응물 4

HCID 65578Oxalyl chlorideHCID 81531DiisopropylethylamineHCID 667368904-(4-Methylpiperazin-1-yl)-2-nitrobenzoic acid hydrochlorideHCID 68670918(3-amino-1-trityl-1H-indazol-5-yl)(3,5-difluorophenyl)methanone

생성물 1

HCID 68671004N-(5-(3,5-Difluorobenzoyl)-1-trityl-1H-indazol-3-yl)-4-(4-methylpiperazin-1-yl)-2-nitrobenzamide수율 92.7%

시약·촉매·용매 2

HCID 6228Dimethylformamide촉매HCID 8028Tetrahydrofuran용매2회

실험 절차

To a suspension of 4-(4-methyl-piperazin-1-yl)-2-nitro-benzoic acid hydrochloride (1.5 g, 4.97 mmol) in dry tetrahydrofuran (80 mL) were added oxalyl chloride (1.4 mL, 19.9 mmol) and N,N-dimethylformamide (1-2 drops). The mixture was stirred at room temperature overnight and then evaporated to dryness. The resulting crude acyl chloride was taken-up with toluene and evaporated again then dissolved in dry tetrahydrofuran (180 mL). A solution of (3-amino-1-trityl-1H-indazol-5-yl)-(3,5-difluoro-phenyl)-methanone (1.83 g. 3.55 mmol) and N,N-diisopropylethylamine (2.5 mL, 14.22 mmol) in dry tetrahydrofuran (15 mL) was added to the reaction mixture. The mixture was stirred at room temperature overnight and then at 75° C. for 2 hours. The volatiles were evaporated and the residue taken up with dichloromethane and washed with brine. The organic phase was dried over sodium sulfate and evaporated to dryness. Purification of the crude by chromatography over silica gel (DCM/MeOH) afforded 2.51 g of the title compound as as yellow powder (92% yield).

후처리

  1. customevaporated to dryness
  2. customevaporated again
  3. dissolutionthen dissolved in dry tetrahydrofuran (180 mL)
  4. stirringThe mixture was stirred at room temperature overnight
  5. waitat 75° C. for 2 hours
  6. customThe volatiles were evaporated
  7. washwashed with brine
  8. dry with materialThe organic phase was dried over sodium sulfate
  9. customevaporated to dryness
  10. customPurification of the crude by chromatography over silica gel (DCM/MeOH)

출처 및 근거

ORD 기록
ord-a24c83da51e14e3aa208a1738897f71e
출처 데이터셋
uspto-grants-2015_05
특허 번호
US09029356B2

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