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1,2-Dichloroethane → 2'-Oxo-N-{(7R)-8-oxo-9-[4-(trifluoromethyl)benzyl]-3,6,7,8,9,10-hexahydroazepino[3,4-e]indazol-7-yl}-1',2',5,7-tetrahydrospiro[cyclopenta[c]pyridine-6,3'-pyrrolo[2,3-b]pyridine]-3-carboxamide

HRID 552566
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HRID 552566 반응식
[NH2:1][C@H:2]1[C:15](=[O:16])[N:14]([CH2:17][C:18]2[CH:23]=[CH:22][C:21]([C:24]([F:27])([F:26])[F:25])=[CH:20][CH:19]=2)[CH2:13][C:5]2[C:6]3[CH:7]=[N:8][NH:9][C:10]=3[CH:11]=[CH:12][C:4]=2[CH2:3]1.[O:28]=[C:29]1[NH:37][C:32]2=[N:33][CH:34]=[CH:35][CH:36]=[C:31]2[C:30]21[CH2:48][C:40]1[CH:41]=[N:42][C:43]([C:45](O)=[O:46])=[CH:44][C:39]=1[CH2:38]2.C1C=CC2N(O)N=NC=2C=1.C(Cl)CCl>CN(C=O)C>[O:28]=[C:29]1[NH:37][C:32]2=[N:33][CH:34]=[CH:35][CH:36]=[C:31]2[C:30]21[CH2:48][C:40]1[CH:41]=[N:42][C:43]([C:45]([NH:1][C@H:2]3[C:15](=[O:16])[N:14]([CH2:17][C:18]4[CH:23]=[CH:22][C:21]([C:24]([F:26])([F:25])[F:27])=[CH:20][CH:19]=4)[CH2:13][C:5]4[C:6]5[CH:7]=[N:8][NH:9][C:10]=5[CH:11]=[CH:12][C:4]=4[CH2:3]3)=[O:46])=[CH:44][C:39]=1[CH2:38]2
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참가 물질

6

반응물 4

HCID 111,2-DichloroethaneHCID 757711-HydroxybenzotriazoleHCID 57974027(+/-)-2'-Oxo-1',2',5,7-tetrahydrospiro[cyclopenta[c]pyridine-6,3'-pyrrolo[2,3-b]pyridine]-3-carboxylic acid2회HCID 597318587-(R)-amino-9-(4-trifluoromethylbenzyl)-6,7,9,10-tetrahydro-3H-2,3,9-triazacyclohepta[e]inden-8-one

생성물 1

HCID 24987068
2'-Oxo-N-{(7R)-8-oxo-9-[4-(trifluoromethyl)benzyl]-3,6,7,8,9,10-hexahydroazepino[3,4-e]indazol-7-yl}-1',2',5,7-tetrahydrospiro[cyclopenta[c]pyridine-6,3'-pyrrolo[2,3-b]pyridine]-3-carboxamide

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

실험 절차

A mixture of 7-(R)-amino-9-(4-trifluoromethylbenzyl)-6,7,9,10-tetrahydro-3H-2,3,9-triazacyclohepta[e]inden-8-one (86 mg, 0.23 mmol) [Chaturvedula et al. WO 2006/052378], (±)-2′-oxo-1′,2′,5,7-tetrahydrospiro[cyclopenta[c]pyridine-6,3′-pyrrolo[2,3-b]pyridine]-3-carboxylic acid (79 mg, 0.28 mmol, described in Intermediate 5), 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-96afd459da864c978f67aaa4905211ac
출처 데이터셋
uspto-grants-2011_05
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US07951795B2

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