Toluene → tert-butyl 9-(2-(3-chloro-2-(pyridin-4-ylcarbamoyl)-1H-pyrrol-1-ylamino)-2-oxoethyl)-9H-purin-6-ylcarbamate

HRID 525048

반응식

HRID 525048 반응식
[NH2:1][C:2]1[CH:7]=[CH:6][N:5]=[CH:4][CH:3]=1.C[Al](C)C.C1(C)C=CC=CC=1.[Cl:19][C:20]1[CH:21]=[CH:22][N:23]2[C:28]=1[C:27](=[O:29])[O:26][C:25]([CH2:30][N:31]1[CH:39]=[N:38][C:37]3[C:32]1=[N:33][CH:34]=[N:35][C:36]=3[N:40](C(OC(C)(C)C)=O)[C:41]([O:43][C:44]([CH3:47])([CH3:46])[CH3:45])=[O:42])=[N:24]2.O.O.C(C(C(C([O-])=O)O)O)([O-])=O.[Na+].[Na+]>ClCCl.O>[Cl:19][C:20]1[CH:21]=[CH:22][N:23]([NH:24][C:25](=[O:26])[CH2:30][N:31]2[CH:39]=[N:38][C:37]3[C:32]2=[N:33][CH:34]=[N:35][C:36]=3[NH:40][C:41](=[O:42])[O:43][C:44]([CH3:47])([CH3:45])[CH3:46])[C:28]=1[C:27](=[O:29])[NH:1][C:2]1[CH:7]=[CH:6][N:5]=[CH:4][CH:3]=1

참가 물질

8

반응물 5

HCID 1140TolueneHCID 17274-AminopyridineHCID 517351Sodium tartrate-2-hydrateHCID 16682925TrimethylaluminumHCID 70922312di-tert-butyl 9-((5-chloro-4-oxo-4H-pyrrolo[1,2-d][1,3,4]oxadiazin-2-yl)methyl)-9H-purin-6-ylimidodicarbonate

생성물 1

HCID 70922268tert-butyl 9-(2-(3-chloro-2-(pyridin-4-ylcarbamoyl)-1H-pyrrol-1-ylamino)-2-oxoethyl)-9H-purin-6-ylcarbamate수율 93.6%

시약·촉매·용매 2

HCID 962Water용매HCID 6344Dichloromethane용매2회

실험 절차

To a suspension of 4-aminopyridine (164 mg, 1.74 mmol) in 3.3 mL of dichloromethane under inert atmosphere was added a 2M solution of trimethyl aluminium in toluene (0.87 mL, 1.74 mmol) and the mixture was stirred during 20 minutes at room temperature. Next, this mixture was cooled in an ice-water bath and a solution of di-tert-butyl 9-((5-chloro-4-oxo-4H-pyrrolo[1,2-d][1,3,4]oxadiazin-2-yl)methyl)-9H-purin-6-ylimidodicarbonate (150 mg, 0.29 mmol) in 2.2 mL of dry dichloromethane was added stirring the mixture during 3 days at room temperature. At the end of this period, the reaction mixture was cooled-down with an ice-water bath and mL of water were added followed by a 5% aqueous solution disodium tartrate dihydrate. The resulting mixture was purified directly by reverse phase chromatography (C-18 silica from Waters, water/1:1 acetonitrile-methanol as eluents 0% to 100%). After purification were obtained 139 mg of tert-butyl 9-(2-(3-chloro-2-(pyridin-4-ylcarbamoyl)-1H-pyrrol-1-ylamino)-2-oxoethyl)-9H-purin-6-ylcarbamate (93% yield).

후처리

  1. temperatureNext, this mixture was cooled in an ice-water bath
  2. stirringstirring the mixture during 3 days at room temperature
  3. temperatureAt the end of this period, the reaction mixture was cooled-down with an ice-water bath
  4. customThe resulting mixture was purified directly by reverse phase chromatography (C-18 silica from Waters, water/1:1 acetonitrile-methanol as eluents 0% to 100%)
  5. customAfter purification

출처 및 근거

ORD 기록
ord-bb4ce3d52fed455798ec7d2d727aeb89
출처 데이터셋
uspto-grants-2016_05
특허 번호
US09340547B2

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