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Diisopropylethylamine → (2e)-3-[4-({[1-({[3-Cyclohexyl-1-[2-(dimethylamino)-2-oxoethyl]-2-(4-methoxyphenyl)-1h-indol-6-yl]carbonyl}amino)cyclopentyl]carbonyl}amino)-phenyl]acrylic acid

HRID 1713932
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HRID 1713932 반응식
[CH:1]1([C:7]2[C:15]3[C:10](=[CH:11][C:12]([C:16](O)=[O:17])=[CH:13][CH:14]=3)[N:9]([CH2:19][C:20]([N:22]([CH3:24])[CH3:23])=[O:21])[C:8]=2[C:25]2[CH:30]=[CH:29][C:28]([O:31][CH3:32])=[CH:27][CH:26]=2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[NH2:66][C:67]1([C:72]([NH:74][C:75]2[CH:80]=[CH:79][C:78](/[CH:81]=[CH:82]/[C:83]([O:85]CC)=[O:84])=[CH:77][CH:76]=2)=[O:73])[CH2:71][CH2:70][CH2:69][CH2:68]1>CN(C=O)C.CCOC(C)=O>[CH:1]1([C:7]2[C:15]3[C:10](=[CH:11][C:12]([C:16]([NH:66][C:67]4([C:72]([NH:74][C:75]5[CH:76]=[CH:77][C:78](/[CH:81]=[CH:82]/[C:83]([OH:85])=[O:84])=[CH:79][CH:80]=5)=[O:73])[CH2:68][CH2:69][CH2:70][CH2:71]4)=[O:17])=[CH:13][CH:14]=3)[N:9]([CH2:19][C:20]([N:22]([CH3:23])[CH3:24])=[O:21])[C:8]=2[C:25]2[CH:30]=[CH:29][C:28]([O:31][CH3:32])=[CH:27][CH:26]=2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1
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참가 물질

7

반응물 4

HCID 81531DiisopropylethylamineHCID 52754503-Cyclohexyl-1-dimethylcarbamoylmethyl-2-(4-methoxy-phenyl)-1H-indole-6-carboxylic acidHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 58745796Ethyl (2E)-3-(4-{[(1-aminocyclopentyl)carbonyl]amino}phenyl)acrylate

생성물 1

HCID 11498502
(2e)-3-[4-({[1-({[3-Cyclohexyl-1-[2-(dimethylamino)-2-oxoethyl]-2-(4-methoxyphenyl)-1h-indol-6-yl]carbonyl}amino)cyclopentyl]carbonyl}amino)-phenyl]acrylic acid
수율 11%

시약·촉매·용매 2

HCID 6228Dimethylformamide용매HCID 8857Ethyl Acetate용매

반응 조건

온도
25 °C

실험 절차

A solution (0.04 M) of 3-cyclohexyl-1-[2-(dimethylamino)-2-oxoethyl]-2-(4 methoxyphenyl)-1H-indole-6-carboxylic acid (from Step 4) in DMF was treated with DIPEA (3 eq.), HATU (2 eq.) and ethyl (2E)-3-(4-{[(1-aminocyclopentyl)carbonyl]amino}phenyl)acrylate (1.1 eq.). The solution was stirred at 25° C. for 12 h. The mixture was diluted with EtOAc then washed sequentially with aqueous HCl (1N), NaOH (2 N) and brine. The dried organic layer was concentrated and the residue dissolved in a solution 1:1 of THF/H2O. The resulting solution was treated with LiOH monohydrate (3 eq.) and stirred at 50° C. for 5 h. The mixture was concentrated under reduced pressure and the residue was treated with aqueous HCl (1 N). Purification by HPLC (stationary phase: Water Symmetry C18 19×300 mm) gave the title compound (11%) as a solid. 1H NMR (400 MHz, DMSO-d6, 300K) δ 1.11-1.40 (m, 3H), 1.62-1.91 (m, 11H), 2.05-2.16 (m, 2H), 2.28-2.44 (m, 2H), 2.50-2.62 (m, 1H), 2.80 (s, 3H), 2.92 (s, 3H), 3.85 (s, 3H), 4.83 (s, 2H), 6.40 (d, J 16.0, 1H), 7.08 (d, J 8.6, 2H), 7.24 (d, J 8.6, 2H), 7.52 (d, J 16.0, 1H), 7.60 (d, J 8.3, 2H), 7.66 (d, J 8.3, 2H), 7.71 (d, J 8.3, 1H), 7.78 (d, J 8.3, 1H), 7.83 (s, 1H), 8.26 (s, 1H), 9.67 (s, 1H), 12.40 (br s, 1H); MS (ES+) m/z 691 (M+H)+.

후처리

  1. washthen washed sequentially with aqueous HCl (1N), NaOH (2 N) and brine
  2. concentrationThe dried organic layer was concentrated
  3. dissolutionthe residue dissolved in a solution 1:1 of THF/H2O
  4. stirringstirred at 50° C. for 5 h
  5. concentrationThe mixture was concentrated under reduced pressure
  6. additionthe residue was treated with aqueous HCl (1 N)
  7. customPurification by HPLC (stationary phase: Water Symmetry C18 19×300 mm)

출처 및 근거

ORD 기록
ord-7a1a3c57f3a54fe4b2433a4625625bf8
출처 데이터셋
uspto-grants-2010_09
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US07795250B2

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