Dicyclohexylcarbodiimide → HCID 178480883, 화합물

HRID 624804노트

반응식

HRID 624804 반응식
[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([F:32])=[C:6]([NH:8][C:9]2[CH:14]=[C:13]([NH:15][CH:16]3[CH2:18][CH2:17]3)[N:12]3[N:19]=[CH:20][C:21](/[CH:22]=[C:23]4/[C:24](=[O:31])[N:25]([CH2:29][OH:30])[C:26](=[O:28])[NH:27]/4)=[C:11]3[N:10]=2)[CH:7]=1.[CH3:33][N:34]1[CH2:39][CH2:38][N:37]([CH2:40][CH2:41][C:42](O)=[O:43])[CH2:36][CH2:35]1.C1(N=C=NC2CCCCC2)CCCCC1>CN(C=O)C.CN(C1C=CN=CC=1)C.C(OCC)(=O)C>[CH3:33][N:34]1[CH2:39][CH2:38][N:37]([CH2:40][CH2:41][C:42]([O:30][CH2:29][N:25]2[C:24](=[O:31])/[C:23](=[CH:22]/[C:21]3[CH:20]=[N:19][N:12]4[C:13]([NH:15][CH:16]5[CH2:17][CH2:18]5)=[CH:14][C:9]([NH:8][C:6]5[CH:7]=[C:2]([Cl:1])[CH:3]=[CH:4][C:5]=5[F:32])=[N:10][C:11]=34)/[NH:27][C:26]2=[O:28])=[O:43])[CH2:36][CH2:35]1

참가 물질

7

반응물 3

HCID 10868DicyclohexylcarbodiimideHCID 13953803-(4-Methylpiperazin-1-yl)propanoic acidHCID 178517689HCID 178517689, 화합물

생성물 1

HCID 178480883HCID 178480883, 화합물수율 26.2%

시약·촉매·용매 3

HCID 142844-(Dimethylamino)pyridine촉매HCID 6228Dimethylformamide용매HCID 8857Ethyl Acetate용매

실험 절차

To (Z)-5-((5-(5-chloro-2-fluorophenylamino)-7-(cyclopropylamino)pyrazolo[1,5-a]pyrimidin-3-yl)methylene)-3-(hydroxymethyl)imidazolidine-2,4-dione (100 mg, 0.218 mmol) in DMF (3 mL) was added 3-(4-methylpiperazin-1-yl)propanoic acid (75 mg, 0.436 mmol), dicyclohexylcarbodiimide (90 mg, 0.436 mmol), and DMAP (4.0 mg, 0.33 mmol). The reaction mixture was stirred at room temperature overnight and then diluted with ethyl acetate and washed 1× water, 3× brine. The organic layer was dried with MgSO4, filtered and adsorbed onto silica gel. The crude material was purified by column chromatography eluting with 0-10% MeOH/CH2Cl2 gradient. Pure fractions were combined and the solvent was removed. This material was crystallized from ethyl acetate and hexane to provide 35 mg (26%) of (Z)-(4-((5-(5-chloro-2-fluorophenylamino)-7-(cyclopropylamino)pyrazolo[1,5-a]pyrimidin-3-yl)methylene)-2,5-dioxoimidazolidin-1-yl)methyl 3-(4-methylpiperazin-1-yl)propanoate as a yellow solid. LCMS (ES): >95% pure, m/z 612 [M+1]+.

후처리

  1. washwashed 1× water, 3× brine
  2. dry with materialThe organic layer was dried with MgSO4
  3. filtrationfiltered
  4. customThe crude material was purified by column chromatography
  5. washeluting with 0-10% MeOH/CH2Cl2 gradient
  6. customthe solvent was removed
  7. customThis material was crystallized from ethyl acetate and hexane

출처 및 근거

ORD 기록
ord-d164bf10730342b988c9adbe5762e274
출처 데이터셋
uspto-grants-2016_04
특허 번호
US09303033B2

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