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1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → N-carbamoylmethyl-1'-[(1-cyclopropyl-4-methoxy-1H-indol-6-yl)carbonyl]-4-oxo-spiro[chroman-2,4'-piperidine]-6-carboxamide

HRID 420134
ノート
印刷プレビュー

反応式

HRID 420134 の反応式
C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.[CH:22]1([N:25]2[C:33]3[C:28](=[C:29]([O:37][CH3:38])[CH:30]=[C:31]([C:34]([OH:36])=O)[CH:32]=3)[CH:27]=[CH:26]2)[CH2:24][CH2:23]1.Cl.[C:40]([CH2:43][NH:44][C:45]([C:47]1[CH:48]=[C:49]2[C:59](=[CH:60][CH:61]=1)[O:58][C:52]1([CH2:57][CH2:56][NH:55][CH2:54][CH2:53]1)[CH2:51][C:50]2=[O:62])=[O:46])(=[O:42])[NH2:41]>CN(C=O)C.O.CCN(CC)CC>[C:40]([CH2:43][NH:44][C:45]([C:47]1[CH:48]=[C:49]2[C:59](=[CH:60][CH:61]=1)[O:58][C:52]1([CH2:57][CH2:56][N:55]([C:34]([C:31]3[CH:32]=[C:33]4[C:28]([CH:27]=[CH:26][N:25]4[CH:22]4[CH2:23][CH2:24]4)=[C:29]([O:37][CH3:38])[CH:30]=3)=[O:36])[CH2:54][CH2:53]1)[CH2:51][C:50]2=[O:62])=[O:46])(=[O:42])[NH2:41]
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

8

反応物 4

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 666494031-cyclopropyl-4-methoxy-1H-indole-6-carboxylic acidHCID 66649519N-Carbamoylmethyl-4-oxospiro[chroman-2,4'-piperidine]-6-carboxamide hydrochloride

生成物 1

HCID 24966803N-carbamoylmethyl-1'-[(1-cyclopropyl-4-methoxy-1H-indol-6-yl)carbonyl]-4-oxo-spiro[chroman-2,4'-piperidine]-6-carboxamide

試薬・触媒・溶媒 3

HCID 962Water溶媒HCID 6228Dimethylformamide溶媒HCID 8471Triethylamine溶媒

反応条件

温度
50 °C

実験手順

Et3N (209 uL), HOBT (91.2 mg) and WSC (115 mg) were added to a suspension of 1-cyclopropyl-4-(methyloxy)-1H-indole-6-carboxylic acid (145 mg) and N-carbamoylmethyl-4-oxo-spiro[chroman-2,4′-piperidine]-6-carboxamide hydrochloride (354 mg) in DMF (3 mL), and the mixture was stirred overnight at 50° C. After cooled to room temperature, the mixture was diluted with water, and the formed solid was collected by filtration. The solid was dried and purified on silica gel preparative TLC (development: CHCl3/MeOH) to obtain the intended compound as colorless foam. 1H-NMR (400 MHz, DMSO-d6) δ: 8.84-8.72 (1H, m), 8.80-8.62 (1H, m), 8.33-8.29 (1H, m), 8.08 (1H, dd, J=8.7, 2.3 Hz), 7.35 (1H, s), 7.28 (1H, d, J=3.2 Hz), 7.23-7.16 (2H, m), 6.99 (1H, s), 6.58 (1H, d, J=1.0 Hz), 6.39 (1H, dd, J=3.2, 0.7 Hz), 4.40-4.02 (2H, br m), 3.87 (3H, s), 3.80-3.76 (2H, br m), 3.48-3.25 (4H, m), 2.98 (2H, s), 2.06-1.56 (2H, m), 1.09-1.01 (2H, m), 0.95-0.89 (2H, m); MS [M+H]+=531.

後処理

  1. temperatureAfter cooled to room temperature
  2. filtrationthe formed solid was collected by filtration
  3. customThe solid was dried
  4. custompurified on silica gel preparative TLC (development: CHCl3/MeOH)

出典と根拠

ORDレコード
ord-f40826c187444959b1b3e91431d2be16
出典データセット
uspto-grants-2012_01
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US08093389B2

反応ノート

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