Potassium Hydroxide → 5-[2-(Tert-butyldimethylsiloxy)ethyl]-4-chloro-7-[2-c-methyl-3,5-bis-o-(2,4-dichlorophenylmethyl)-beta-d-ribofuranosyl]-7h-pyrrolo[2,3-d]pyrimidine

HRID 915865노트

반응식

HRID 915865 반응식
[O:1]([CH2:9][CH2:10][C:11]1[C:19]2[C:18]([Cl:20])=[N:17][CH:16]=[N:15][C:14]=2[NH:13][CH:12]=1)[Si:2]([C:5]([CH3:8])([CH3:7])[CH3:6])([CH3:4])[CH3:3].[OH-].[K+].COCCOCCN(CCOCCOC)CCOCCOC.[Cl:45][C:46]1[CH:51]=[C:50]([Cl:52])[CH:49]=[CH:48][C:47]=1[CH2:53][O:54][C@@H:55]1[C@@H:61]([CH2:62][O:63][CH2:64][C:65]2[CH:70]=[CH:69][C:68]([Cl:71])=[CH:67][C:66]=2[Cl:72])[O:60][C@H:57](OC)[C@:56]1([CH3:74])[OH:73]>CC#N.O.C(Cl)Cl>[O:1]([CH2:9][CH2:10][C:11]1[C:19]2[C:18]([Cl:20])=[N:17][CH:16]=[N:15][C:14]=2[N:13]([C@@H:57]2[O:60][C@H:61]([CH2:62][O:63][CH2:64][C:65]3[CH:70]=[CH:69][C:68]([Cl:71])=[CH:67][C:66]=3[Cl:72])[C@@H:55]([O:54][CH2:53][C:47]3[CH:48]=[CH:49][C:50]([Cl:52])=[CH:51][C:46]=3[Cl:45])[C@@:56]2([CH3:74])[OH:73])[CH:12]=1)[Si:2]([C:5]([CH3:6])([CH3:7])[CH3:8])([CH3:3])[CH3:4]

참가 물질

8

반응물 4

HCID 14797Potassium HydroxideHCID 112414Ethanamine, 2-(2-methoxyethoxy)-N,N-bis[2-(2-methoxyethoxy)ethyl]-HCID 104952735-[2-(tert-Butyldimethylsiloxy)ethyl]-4-chloro-7H-pyrrolo[2,3-d]pyrimidineHCID 11283339Methyl 3,5-bis-O-((2,4-dichlorophenyl)methyl)-2-C-methyl-alpha-D-ribofuranoside

생성물 1

HCID 875172625-[2-(Tert-butyldimethylsiloxy)ethyl]-4-chloro-7-[2-c-methyl-3,5-bis-o-(2,4-dichlorophenylmethyl)-beta-d-ribofuranosyl]-7h-pyrrolo[2,3-d]pyrimidine수율 13%

시약·촉매·용매 3

HCID 962Water용매HCID 6342Acetonitrile용매2회HCID 6344Dichloromethane용매

실험 절차

Compound 2.3 (2.5 g, 8.00 mmol) was suspended in CH3CN (50 mL), and powdered 85% KOH, (1.3 g, 19.73 mmol) followed by TDA -1 (tris[2-(2-methoxyethoxy)ethyl]amine) (0.2 mL, 0.62 mmol) were added. After stirring at room temperature for 10 min, a freshly prepared solution of bromo sugar 2.4 (prepared from commercially available 3,5-bis-O-(2,4-dichlorophenylmethyl)-2-C-methyl-1-O-methyl-α-D-ribofuranose; (i) Helv. Chim. Acta, 1995, 78, 486; (ii) WO 02/057287, 2002) (10.1 mmol) in anhydrous acetonitrile (50 mL) was added via cannula, and the reaction stirred for 24 hr at room temperature then cooled in an ice/water bath and treated with CH2Cl2 (100 mL) and water (80 mL). The aqueous material was extracted three times with CH2Cl2, the combined organic layers were dried over Na2SO4, filtered and evaporated The crude product was purified on a silica gel column using 20% ethyl acetate/hexanes as eluent to give the desired nucleoside 2.5 (1.03 g, 13%). Further elution with 25% EtOAc/hexanes as eluent gave a mixture of the desired nucleoside 2.5 and starting base 2.3 (350 mg).

후처리

  1. additionwere added
  2. additionwas added via cannula
  3. stirringthe reaction stirred for 24 hr at room temperature
  4. temperaturethen cooled in an ice/water bath
  5. extractionThe aqueous material was extracted three times with CH2Cl2
  6. dry with materialthe combined organic layers were dried over Na2SO4
  7. filtrationfiltered
  8. customevaporated The crude product
  9. customwas purified on a silica gel column

출처 및 근거

ORD 기록
ord-4609062db93b4bd8b42993573b6ab4ac
출처 데이터셋
uspto-grants-2007_09
특허 번호
US07268119B2

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