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Ammonium Hydroxide → 5-methylseleno-3'-t-butyldimethylsilyl-5'-O-(4,4-dimethoxytrityl)-2'-deoxycytidine

HRID 2406285
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HRID 2406285 반응식
[CH3:1][Se:2][C:3]1[C:4](=O)[NH:5][C:6](=[O:47])[N:7]([CH:46]=1)[C@@H:8]1[O:38][C@H:12]([CH2:13][O:14][C:15]([C:32]2[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=2)([C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)[C:16]2[CH:21]=[CH:20][C:19]([O:24][CH3:25])([O:22][CH3:23])[CH2:18][CH:17]=2)[C@@:10]([Si:39]([C:42]([CH3:45])([CH3:44])[CH3:43])([CH3:41])[CH3:40])([OH:11])[CH2:9]1.C([N:52](C(C)C)CC)(C)C.C(C1C=CC(S(Cl)(=O)=O)=C(C(C)C)C=1C(C)C)(C)C.[OH-].[NH4+]>C(#N)C.CN(C)C1C=CN=CC=1.C(Cl)Cl.CO.C(OCC)(=O)C.CCCCCC>[CH3:1][Se:2][C:3]1[C:4]([NH2:52])=[N:5][C:6](=[O:47])[N:7]([CH:46]=1)[C@@H:8]1[O:38][C@H:12]([CH2:13][O:14][C:15]([C:26]2[CH:27]=[CH:28][CH:29]=[CH:30][CH:31]=2)([C:32]2[CH:33]=[CH:34][CH:35]=[CH:36][CH:37]=2)[C:16]2[CH:21]=[CH:20][C:19]([O:22][CH3:23])([O:24][CH3:25])[CH2:18][CH:17]=2)[C@@:10]([Si:39]([C:42]([CH3:43])([CH3:45])[CH3:44])([CH3:40])[CH3:41])([OH:11])[CH2:9]1
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참가 물질

10

반응물 4

HCID 14923Ammonium HydroxideHCID 81531DiisopropylethylamineHCID 11514985Triisopropylbenzenesulfonyl chlorideHCID 1317317735-methylseleno-3'-t-butyldimethylsilyl-5'-O-(4,4-dimethoxytrityl)-2'-deoxyuridine

생성물 1

HCID 1317317725-methylseleno-3'-t-butyldimethylsilyl-5'-O-(4,4-dimethoxytrityl)-2'-deoxycytidine수율 64.9%

시약·촉매·용매 5

HCID 142844-(Dimethylamino)pyridine촉매HCID 887Methanol용매HCID 6342Acetonitrile용매HCID 6344Dichloromethane용매HCID 21226206Ethyl acetate hexane용매

실험 절차

After 5-methylseleno-3′-t-butyldimethylsilyl-5′-O-(4,4-dimethoxytrityl)-2′-deoxyuridine 480 mg (MW 752.2, 0.64 mmol) was dissolved in acetonitrile 10 ml, diisopropylethyl amine (0.67 ml, 3.19 mmol, 5 eq.), triisopropylbenzenesulfonyl chloride (576 mg, 1.59 mmol, 2.5 eq.) and p-dimethylamino pyridine (96 mg, 0.64 mmol, 1 eq.) were added sequentially. The reaction mixture was stirred for 16 hours and monitored on TLC (ethyl acetate/hexane, 3:7). After completion, excessive concentrated ammonium hydroxide solution was added dropwise and the reaction was stirred under room temperature for 1 hour. After the reaction was completed (monitored on TLC, 5% MeOH in CH2Cl2, Rf=5), the organic solvent and ammonium hydroxide were evaporated under reduced pressure. A silica gel column was equilibrated with CH2Cl2 before the crude product was loaded and purified on the column. The product was eluded by MeOH in CH2Cl2 (1-7%). The fractions containing the product were combined, evaporated and dried on high vacuum overnight to yield yellow solid 307 mg. (yield=64%). 1H-NMR (400 MHz, DMSO) δ: 0.05 (s, 6H, SiCH3), 0.87 (s, 9H, t-butyl), 1.95 (s, 3H, SeCH3), 2.18-2.25 and 2.58-2.62 (2×m, 2H, H-2′), 3.30-3.33 and 3.46-3.49 (2×m, 2H, H-5′), 3.84 (s, 6H, 2×OMe), 4.03-4.08 (m, 1H, H-3′), 4.42-4.46 (m, 1H, H-4′), 6.11 (s, 1H, NH2), 6.28-631 (t, J=5.6 Hz, 1H, H-1′), 6.50 (s, 1H, NH2), 6.86-7.48 (m, 13H, arom-H), 8.30 (s, 1H, H-6). 13C NMR (100 MHz, DMSO) δ: −4.86 and −4.69 [Si(CH3)2], 7.31 (SeCH3), 17.96 [SiC(CH3)], 25.74 [SiC(CH3)], 41.74 (C-2′), 55.26 (OMe), 62.88 (C-5′), 72.23 (C-3′), 85.55 (C-4′), 87.05 (arom-C), 87.16 (C-1′), 103.45 (C-5), 113.23 (arom-C), 126.94 Carom-C), 128.15 (arom-C), 130.11 (arom-C), 135.50 (arom-C), 141.74 (C-6), 144.41 (arom-C), 149.89 (C-2), 155.46 (arom-C), 158.66 (C-4), 161.46 (arom-C), 165.55 (arom-C). HR-MS (ESI-TOF, positive ion mode): molecular formula, C32H47N3O6SeSi: [M+H]−: 738.2468 (calc. 738.2478).

후처리

  1. stirringthe reaction was stirred under room temperature for 1 hour
  2. customthe organic solvent and ammonium hydroxide were evaporated under reduced pressure
  3. custompurified on the column
  4. additionThe fractions containing the product
  5. customevaporated
  6. customdried on high vacuum overnight

출처 및 근거

ORD 기록
ord-369b37c9c2e34c3fb2a1b88155b460f8
출처 데이터셋
uspto-grants-2014_08
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08809357B2

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