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llms.txt · MCP 가이드개인정보처리방침 · 이용약관 · 지원v1.8.0
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Triethylamine → (R)-4-(2-oxo-2,3-dihydroimidazo[4,5-b]pyridin-1-yl)-N-(2-oxo-5-phenyl-1-(2,2,2-trifluoroethyl)-2,3-dihydro-1H-benzo[e][1,4]diazepin-3-yl)piperidine-1-carboxamide

HRID 1453959
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HRID 1453959 반응식
[NH2:1][CH:2]1[N:8]=[C:7]([C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)[C:6]2[CH:15]=[CH:16][CH:17]=[CH:18][C:5]=2[N:4]([CH2:19][C:20]([F:23])([F:22])[F:21])[C:3]1=[O:24].C1C([N+]([O-])=O)=CC=C([Cl-][C:35]([O-])=[O:36])C=1.C(N(CC)CC)C.Cl.Cl.[O:47]=[C:48]1[NH:56][C:51]2=[N:52][CH:53]=[CH:54][CH:55]=[C:50]2[N:49]1[CH:57]1[CH2:62][CH2:61][NH:60][CH2:59][CH2:58]1>O1CCCC1.CS(C)=O>[O:24]=[C:3]1[C@H:2]([NH:1][C:35]([N:60]2[CH2:61][CH2:62][CH:57]([N:49]3[C:50]4[C:51](=[N:52][CH:53]=[CH:54][CH:55]=4)[NH:56][C:48]3=[O:47])[CH2:58][CH2:59]2)=[O:36])[N:8]=[C:7]([C:9]2[CH:10]=[CH:11][CH:12]=[CH:13][CH:14]=2)[C:6]2[CH:15]=[CH:16][CH:17]=[CH:18][C:5]=2[N:4]1[CH2:19][C:20]([F:21])([F:23])[F:22]
참가 물질실험 절차후처리출처 및 근거반응 노트

참가 물질

6

반응물 3

HCID 8471Triethylamine2회HCID 107353833-Amino-5-phenyl-1-(2,2,2-trifluoroethyl)-1H-benzo[e][1,4]diazepin-2(3H)-oneHCID 222931811-(piperidin-4-yl)-1H,2H,3H-imidazo[4,5-b]pyridin-2-one dihydrochloride

생성물 1

HCID 11421827(R)-4-(2-oxo-2,3-dihydroimidazo[4,5-b]pyridin-1-yl)-N-(2-oxo-5-phenyl-1-(2,2,2-trifluoroethyl)-2,3-dihydro-1H-benzo[e][1,4]diazepin-3-yl)piperidine-1-carboxamide수율 70.8%

시약·촉매·용매

2
HCID 679Dimethyl Sulfoxide용매HCID 8028Tetrahydrofuran용매

실험 절차

A solution of (3R) 3-amino-2-oxo-5-phenyl-1-(2,2,2-trifluorethyl)-2,3-dihydro-1H-1,4-benzodiazepine (Y.-J. Shi et al., Tetrahedron, 1999, 55, 909-918) (0.150 g, 0.45 mmol) and 4-nitrophenylchloroformate (0.091 g, 0.45 mmol) in dry tetrahydrofuran (2.5 mL) was cooled to 0° C. under argon. Triethylamine (0.063 mL, 0.45 mmol) was added and the reaction stirred for 1 h. A solution of 2-oxo-1-(4-piperidinyl)-2,3-dihydro-1H-imidazo[4,5-b]pyridine dihydrochloride (0.130 g, 0.45 mmol) and triethylamine (0.190 mL) in dimethylsulfoxide (2.5 mL) was added. The reaction was allowed to come to room temperature and stirred overnight. The crude product was purified by reverse phase HPLC (C-18, 5% to 95% 0.1% trifluoroacetic acid/acetonitrile in 0.1% aqueous trifluoroacetic acid gradient elution). The pure fractions were extracted with methylene chloride and saturated sodium bicarbonate. The organic layer was dried, filtered and evaporated. The product was taken up in methanol and treated with hydrogen chloride. The solvent was evaporated and the resulting solid was dried in vacuo, to yield the title compound (184 mg, 66% yield). MS 578.2118 (M+1) 1H NMR (500 MHz, C3OD) δ 8.02 (d, J=8 Hz, 1H), 8.00 (d, J=6 Hz, 1H), 7.80 (d, J=3 Hz, 2H), 7.60 (m, 3H), 7.50 (t, J=8 Hz, 2H), 7.45 (m, 1H), 7.39 (d, J=7 Hz, 1H), 7.34 (dd, J=6, 8 Hz, 1H), 5.55 (s, 1H), 5.26 (m, 1H), 4.61 (m, 2H), 4.35 (d, J=13 Hz, 2H), 3.08 (q, J=13 Hz, 2H), 2.40 (m, 2H), 1.91 (m, 2H).

후처리

  1. customto come to room temperature
  2. stirringstirred overnight
  3. customThe crude product was purified by reverse phase HPLC (C-18, 5% to 95% 0.1% trifluoroacetic acid/acetonitrile in 0.1% aqueous trifluoroacetic acid gradient elution)
  4. extractionThe pure fractions were extracted with methylene chloride and saturated sodium bicarbonate
  5. customThe organic layer was dried
  6. filtrationfiltered
  7. customevaporated
  8. additiontreated with hydrogen chloride
  9. customThe solvent was evaporated
  10. customthe resulting solid was dried in vacuo

출처 및 근거

ORD 기록
ord-3862337397a648efb879507b43fa2df2
출처 데이터셋
uspto-grants-2009_01
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US07476665B2

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