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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
ノート
印刷プレビュー

反応式

HRID 1713932 の反応式
[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
参加物反応条件実験手順後処理出典と根拠反応ノート

参加物

7

反応物 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

生成物 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
収率 11%

試薬・触媒・溶媒 2

HCID 6228Dimethylformamide溶媒HCID 8857Ethyl Acetate溶媒

反応条件

温度
25 °C

実験手順

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)+.

後処理

  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)

出典と根拠

ORDレコード
ord-7a1a3c57f3a54fe4b2433a4625625bf8
出典データセット
uspto-grants-2010_09
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US07795250B2

反応ノート

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