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N-(tert-butoxycarbonyl)glycine → Tert-butyl (2-oxo-2-((3-(4-(propylamino)-2-((2-(pyridin-4-yl)ethyl)amino)pyrimidine-5-carboxamido)propyl)amino)ethyl)carbamate

HRID 2284643
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HRID 2284643 반응식
[NH2:1][CH2:2][CH2:3][CH2:4][NH:5][C:6]([C:8]1[C:9]([NH:23][CH2:24][CH2:25][CH3:26])=[N:10][C:11]([NH:14][CH2:15][CH2:16][C:17]2[CH:22]=[CH:21][N:20]=[CH:19][CH:18]=2)=[N:12][CH:13]=1)=[O:7].[C:27]([NH:34][CH2:35][C:36](O)=[O:37])([O:29][C:30]([CH3:33])([CH3:32])[CH3:31])=[O:28].Cl.C(N=C=NCCCN(C)C)C.O.ON1C2C=CC=CC=2N=N1.C(=O)([O-])O.[Na+]>C(OCC)(=O)C.C(N(CC)CC)C.CN(C)C=O>[O:37]=[C:36]([NH:1][CH2:2][CH2:3][CH2:4][NH:5][C:6]([C:8]1[C:9]([NH:23][CH2:24][CH2:25][CH3:26])=[N:10][C:11]([NH:14][CH2:15][CH2:16][C:17]2[CH:22]=[CH:21][N:20]=[CH:19][CH:18]=2)=[N:12][CH:13]=1)=[O:7])[CH2:35][NH:34][C:27](=[O:28])[O:29][C:30]([CH3:32])([CH3:31])[CH3:33]
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참가 물질

9

반응물 5

HCID 78288N-(tert-butoxycarbonyl)glycineHCID 516892Sodium BicarbonateHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 90052165N-(3-aminopropyl)-4-(propylamino)-2-((2-(pyridin-4-yl)ethyl)amino)pyrimidine-5-carboxamide

생성물 1

HCID 90052168
Tert-butyl (2-oxo-2-((3-(4-(propylamino)-2-((2-(pyridin-4-yl)ethyl)amino)pyrimidine-5-carboxamido)propyl)amino)ethyl)carbamate
수율 101.1%

시약·촉매·용매 3

HCID 6228Dimethylformamide용매HCID 8471Triethylamine용매HCID 8857Ethyl Acetate용매

실험 절차

To N-(3-aminopropyl)-4-(propylamino)-2-((2-(pyridin-4-yl)ethyl)amino)pyrimidine-5-carboxamide (B4, 57 mg), N-Boc-glycine (44 mg), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (127 mg) and 1-hydroxybenzotriazole monohydrate (102 mg), N,N-dimethylformamide (2 mL) and triethylamine (46 μL) were added at room temperature, and the mixture was stirred at the same temperature for 7 hours. To the reaction mixture, saturated aqueous sodium hydrogencarbonate and ethyl acetate were added. The organic layer was separated, and the aqueous layer was extracted with ethyl acetate. The organic layer and the extract were combined, washed successively with water and saturated aqueous sodium chloride, and then dried over anhydrous sodium sulfate, and the solvent was evaporated under reduced pressure. The obtained residue was purified by basic silica gel column chromatography (eluent, 95 to 90% ethyl acetate in methanol) to obtain amorphous tert-butyl (2-oxo-2-((3-(4-(propylamino)-2-((2-(pyridin-4-yl)ethyl)amino)pyrimidine-5-carboxamido)propyl)amino)ethyl)carbamate (B5, 83 mg).

후처리

  1. customThe organic layer was separated
  2. extractionthe aqueous layer was extracted with ethyl acetate
  3. washwashed successively with water and saturated aqueous sodium chloride
  4. dry with materialdried over anhydrous sodium sulfate
  5. customthe solvent was evaporated under reduced pressure
  6. customThe obtained residue was purified by basic silica gel column chromatography (eluent, 95 to 90% ethyl acetate in methanol)

출처 및 근거

ORD 기록
ord-5acda82367284268a9f721b145b40e61
출처 데이터셋
uspto-grants-2015_09
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US09145415B2

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