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Diisopropylethylamine → (2E)-3-[4-({[1-({[3-cyclohexyl-1-[2-(dimethylamino)-2-oxoethyl]-2-(1,3-oxazol-5-yl)-1H-indol-6-yl]carbonyl}amino)cyclopentyl]carbonyl}amino)phenyl]acrylic acid

HRID 1713946
ノート
印刷プレビュー

反応式

HRID 1713946 の反応式
[CH:1]1([C:7]2[C:15]3[C:10](=[CH:11][C:12]([C:16]([OH:18])=O)=[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[O:29][CH:28]=[N: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.[NH2:63][C:64]1([C:69]([NH:71][C:72]2[CH:77]=[CH:76][C:75](/[CH:78]=[CH:79]/[C:80]([O:82]CC)=[O:81])=[CH:74][CH:73]=2)=[O:70])[CH2:68][CH2:67][CH2:66][CH2:65]1>CN(C=O)C.C1COCC1.CO>[CH:1]1([C:7]2[C:15]3[C:10](=[CH:11][C:12]([C:16]([NH:63][C:64]4([C:69]([NH:71][C:72]5[CH:73]=[CH:74][C:75](/[CH:78]=[CH:79]/[C:80]([OH:82])=[O:81])=[CH:76][CH:77]=5)=[O:70])[CH2:68][CH2:67][CH2:66][CH2:65]4)=[O:18])=[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[O:29][CH:28]=[N: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 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 114635753-cyclohexyl-1-[2-(dimethylamino)-2-oxoethyl]-2-(1,3-oxazol-5-yl)-1H-indole-6-carboxylic acidHCID 58745796Ethyl (2E)-3-(4-{[(1-aminocyclopentyl)carbonyl]amino}phenyl)acrylate

生成物 1

HCID 11621612
(2E)-3-[4-({[1-({[3-cyclohexyl-1-[2-(dimethylamino)-2-oxoethyl]-2-(1,3-oxazol-5-yl)-1H-indol-6-yl]carbonyl}amino)cyclopentyl]carbonyl}amino)phenyl]acrylic acid
収率 98%

試薬・触媒・溶媒 2

HCID 6228Dimethylformamide溶媒HCID 21899815MeOH tetrahydrofuran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-(1,3-oxazol-5-yl)-1H-indole-6-carboxylic acid (from Step 6) in DMF was treated with DIPEA (3 eq.), HATU (2 eq.) and ethyl (2E)-3-(4-{[(1-aminocyclopentyl)carbonyl]amino}phenyl)acrylate (from Example 1, Step 7, 1.1 eq.). The solution was stirred at 25° C. for 12 h and then evaporated in vacuo. The residual material was purified by chromatography on silica gel (PE:EtOAc, 8:2, then EtOAc:PE 9:1). The product fractions were evaporated and the material obtained was then dissolved in THF/MeOH (1:1). The resulting solution was treated with LiOH monohydrate (3 eq.) and stirred at RT overnight. The product was isolated by preparative HPLC (stationary phase: Waters Xterra C18 19×150 mm, 5 micron; flow 20 mL/min). After lyophilisation the product was obtained as a colourless amorphous solid (98%).

後処理

  1. customevaporated in vacuo
  2. customThe residual material was purified by chromatography on silica gel (PE
  3. customThe product fractions were evaporated
  4. customthe material obtained
  5. stirringstirred at RT overnight
  6. customThe product was isolated by preparative HPLC (stationary phase: Waters Xterra C18 19×150 mm, 5 micron; flow 20 mL/min)

出典と根拠

ORDレコード
ord-880b96217574481d82e86a3f04e1ab36
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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