1,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochloride → (+/-)-cis-N1-[(5-Chloroindol-2-yl)carbonyl]-N2-[(5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridin-2-yl)carbonyl]-1,2-cyclopropanediamine hydrochloride

HRID 459551노트

반응식

HRID 459551 반응식
O.ON1C2C=CC=CC=2N=N1.Cl.CN(C)CCCN=C=NCC.[Cl:24][C:25]1[CH:26]=[C:27]2[C:31](=[CH:32][CH:33]=1)[NH:30][C:29]([C:34]([NH:36][C@@H:37]1[CH2:39][C@@H:38]1[NH2:40])=[O:35])=[CH:28]2.[CH3:41][N:42]1[CH2:47][CH2:46][C:45]2[N:48]=[C:49]([C:51]([O-])=[O:52])[S:50][C:44]=2[CH2:43]1.[Li+]>CN(C)C=O>[ClH:24].[Cl:24][C:25]1[CH:26]=[C:27]2[C:31](=[CH:32][CH:33]=1)[NH:30][C:29]([C:34]([NH:36][C@@H:37]1[CH2:39][C@@H:38]1[NH:40][C:51]([C:49]1[S:50][C:44]3[CH2:43][N:42]([CH3:41])[CH2:47][CH2:46][C:45]=3[N:48]=1)=[O:52])=[O:35])=[CH:28]2

참가 물질

6

반응물 4

HCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 18442851N-[(1R*,2S*)-2-Aminocyclopropyl]-5-chloroindole-2-carboxamideHCID 23704331Lithium 5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine-2-carboxylate

생성물 1

HCID 68907574(+/-)-cis-N1-[(5-Chloroindol-2-yl)carbonyl]-N2-[(5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridin-2-yl)carbonyl]-1,2-cyclopropanediamine hydrochloride수율 71.4%

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

실험 절차

1-Hydroxybenzotriazole monohydrate (71 mg) and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (100 mg) were added to a solution with (±)-cis-N-[(5-chloroindol-2-yl)carbonyl]-1,2-cyclopropanediamine (108 mg) and lithium 5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine-2-carboxylate (124 mg) dissolved in N,N-dimethylformamide (3 ml) at room temperature, and the mixture was stirred for 8 days. After concentrating the reaction mixture under reduced pressure using a vacuum pump, water (50 ml) and a saturated aqueous solution (50 ml) of sodium hydrogencarbonate were added to the residue to conduct extraction with dichloromethane. The resultant organic layers were collected and dried over anhydrous sodium sulfate, the solvent was distilled off under reduced pressure, and the residue was purified by preparative thin-layer chromatography on silica gel (dichloromethane:methanol=10:1). After 1N hydrochloric acid, dichloromethane and methanol were added to the thus-obtained amorphous substance, the mixture was concentrated to obtain the title compound (72 mg) as a colorless solid.

후처리

  1. concentrationAfter concentrating the reaction mixture under reduced pressure
  2. additiona saturated aqueous solution (50 ml) of sodium hydrogencarbonate were added to the residue
  3. extractionextraction with dichloromethane
  4. customThe resultant organic layers were collected
  5. dry with materialdried over anhydrous sodium sulfate
  6. distillationthe solvent was distilled off under reduced pressure
  7. customthe residue was purified by preparative thin-layer chromatography on silica gel (dichloromethane:methanol=10:1)
  8. additionAfter 1N hydrochloric acid, dichloromethane and methanol were added to the thus-obtained amorphous substance
  9. concentrationthe mixture was concentrated

출처 및 근거

ORD 기록
ord-b2fd3a4f76b64bf7964f13d54bc1aba2
출처 데이터셋
uspto-grants-2007_03
특허 번호
US07192968B2

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