1,2-Dichloroethane → 2-[(7S)-4-Chloro-8-oxo-9-(pyridin-4-ylmethyl)-3,6,7,8,9,10-hexahydroazepino[3,4-e]indazol-7-yl]-N-(3-methyl-2,5-dioxo-1',3'-dihydrospiro[imidazolidine-4,2'-inden]-5'-yl)acetamide

HRID 552563노트

반응식

HRID 552563 반응식
Cl.Cl.[Cl:3][C:4]1[C:12]2[NH:11][N:10]=[CH:9][C:8]=2[C:7]2[CH2:13][N:14]([CH2:23][C:24]3[CH:29]=[CH:28][N:27]=[CH:26][CH:25]=3)[C:15](=[O:22])[C@H:16]([CH2:18][C:19](O)=[O:20])[CH2:17][C:6]=2[CH:5]=1.[NH2:30][C:31]1[CH:32]=[C:33]2[C:37](=[CH:38][CH:39]=1)[CH2:36][C:35]1([C:43](=[O:44])[NH:42][C:41](=[O:45])[N:40]1[CH3:46])[CH2:34]2.C1C=CC2N(O)N=NC=2C=1.C(Cl)CCl>CN(C=O)C>[Cl:3][C:4]1[C:12]2[NH:11][N:10]=[CH:9][C:8]=2[C:7]2[CH2:13][N:14]([CH2:23][C:24]3[CH:25]=[CH:26][N:27]=[CH:28][CH:29]=3)[C:15](=[O:22])[C@H:16]([CH2:18][C:19]([NH:30][C:31]3[CH:32]=[C:33]4[C:37](=[CH:38][CH:39]=3)[CH2:36][C:35]3([C:43](=[O:44])[NH:42][C:41](=[O:45])[N:40]3[CH3:46])[CH2:34]4)=[O:20])[CH2:17][C:6]=2[CH:5]=1

참가 물질

6

반응물 4

HCID 111,2-DichloroethaneHCID 757711-HydroxybenzotriazoleHCID 18440306(-)-5'-Amino-3-methyl-spiro[imidazolidine-4,2'-indane]-2,5-dioneHCID 67202381(S)-2-(4-Chloro-8-oxo-9-(pyridin-4-ylmethyl)-3,6,7,8,9,10-hexahydroazepino[3,4-e]indazol-7-yl)acetic acid dihydrochloride

생성물 1

HCID 249870692-[(7S)-4-Chloro-8-oxo-9-(pyridin-4-ylmethyl)-3,6,7,8,9,10-hexahydroazepino[3,4-e]indazol-7-yl]-N-(3-methyl-2,5-dioxo-1',3'-dihydrospiro[imidazolidine-4,2'-inden]-5'-yl)acetamide

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

실험 절차

A mixture of (S)-2-[4-chloro-8-oxo-9-(pyridine-4-ylmethyl)-3,6,7,8,9,10-hexahydroazepino[3,4-e]indazol-7-yl]acetic acid dihydrochloride (105 mg, 0.23 mmol) [Chaturvedula et al. WO 2006/052378], (±)-5′-amino-3-methyl-spiro[imidazolidine-4,2′-indane]-2,5-dione (65 mg, 0.28 mmol) [Bell et al. WO 2004/082605], HOBT (43 mg, 0.28 mmol), and EDC (54 mg, 0.28 mmol) in DMF (2 mL) is stirred at ambient temperature for 18 h. The reaction mixture is purified directly by HPLC using a reversed phase C18 column and eluting with a gradient of H2O:CH3CN:CF3CO2H-90:10:0.1 to 5:95:0.1. The pure, product-containing fractions are combined and made basic with saturated aqueous NaHCO3. The resulting mixture is extracted with EtOAc (2×20 mL), and the combined organic extracts are washed with brine, dried over Na2SO4, filtered, and concentrated in vacuo to provide the title compound.

후처리

  1. customThe reaction mixture is purified directly by HPLC
  2. washeluting with a gradient of H2O
  3. additionThe pure, product-containing fractions
  4. extractionThe resulting mixture is extracted with EtOAc (2×20 mL)
  5. washthe combined organic extracts are washed with brine
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo

출처 및 근거

ORD 기록
ord-94a82c69e9ae48e49bceaab14ebca5a4
출처 데이터셋
uspto-grants-2011_05
특허 번호
US07951795B2

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