5-Chloro-1H-indole-2-carboxylic acid → (+/-)-trans-N1-[(5-Chloroindol-2-yl)carbonyl]-N2-[(5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridin-2-yl)carbonyl]-1,2-cyclopentanediamine hydrochloride

HRID 459553ノート

反応式

HRID 459553 の反応式
[Cl:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][C:6]([C:11]([OH:13])=O)=[CH:5]2.Cl.CN(C)CCCN=C=NCC.O.ON1C2C=CC=CC=2N=N1.Cl.[CH3:38][N:39]1[CH2:44][CH2:43][C:42]2[N:45]=[C:46]([C:48]([NH:50][C@@H:51]3[CH2:55][CH2:54][CH2:53][C@H:52]3[NH2:56])=[O:49])[S:47][C:41]=2[CH2:40]1>CN(C)C=O.C(N(CC)CC)C>[ClH:1].[Cl:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][C:6]([C:11]([NH:56][C@@H:52]1[CH2:53][CH2:54][CH2:55][C@H:51]1[NH:50][C:48]([C:46]1[S:47][C:41]3[CH2:40][N:39]([CH3:38])[CH2:44][CH2:43][C:42]=3[N:45]=1)=[O:49])=[O:13])=[CH:5]2

参加物

7

反応物 4

HCID 826935-Chloro-1H-indole-2-carboxylic acidHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 18442877N-[(1R*,2R*)-2-Aminocyclopentyl]-5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine-2-carboxamide hydrochloride

生成物 1

HCID 45263647(+/-)-trans-N1-[(5-Chloroindol-2-yl)carbonyl]-N2-[(5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridin-2-yl)carbonyl]-1,2-cyclopentanediamine hydrochloride収率 107.8%

試薬・触媒・溶媒 2

HCID 6228Dimethylformamide溶媒HCID 8471Triethylamine溶媒

実験手順

5-Chloroindole-2-carboxylic acid (80 mg), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (98 mg), 1-hydroxybenzotriazole monohydrate (23 mg) and triethylamine (141 μl) were added to a solution with (±)-trans-N-[(5-methyl-4,5,6,7-tetrahydrothiazolo-[5,4-c]pyridin-2-yl)carbonyl]-1,2-cyclopentanediamine hydrochloride (120 mg) dissolved in N,N-dimethylformamide (5 ml), and the mixture was stirred at room temperature for 3 days. The solvent was distilled off under reduced pressure, and dichloromethane and a saturated aqueous solution of sodium hydrogencarbonate were added to the residue to conduct liquid separation. The resultant organic layer was dried over anhydrous sodium sulfate, the solvent was distilled off under reduced pressure, and the residue was purified by flash column chromatography on silica gel (dichloromethane:methanol=93:7). After dichloromethane (5 ml) and a 1N ethanol solution (282 μl) of hydrochloric acid were added to the thus-obtained pale yellow solid. Ethyl acetate was added, solvent was distilled off under reduced pressure and precipitate formed was collected by filtration to obtain the title compound (109 mg) as a pale yellow solid.

後処理

  1. distillationThe solvent was distilled off under reduced pressure, and dichloromethane
  2. additiona saturated aqueous solution of sodium hydrogencarbonate were added to the residue
  3. customliquid separation
  4. dry with materialThe resultant organic layer was dried over anhydrous sodium sulfate
  5. distillationthe solvent was distilled off under reduced pressure
  6. customthe residue was purified by flash column chromatography on silica gel (dichloromethane:methanol=93:7)
  7. additionAfter dichloromethane (5 ml) and a 1N ethanol solution (282 μl) of hydrochloric acid were added to the thus-obtained pale yellow solid
  8. additionEthyl acetate was added
  9. distillationsolvent was distilled off under reduced pressure and precipitate
  10. customformed
  11. filtrationwas collected by filtration

出典と根拠

ORDレコード
ord-f29bac67614c4c33be16560ad4ec7946
出典データセット
uspto-grants-2007_03
特許番号
US07192968B2

反応ノート

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