N,N-Diphenylcarbamic chloride → N2-isobutyryl-O6-diphenylcarbamoyl-3'-O-(methylthiomethyl)-5'-O-(tert-butyldimethylsilyl)-2'-deoxyguanosine

HRID 58512

Reaction equation

HRID 58512 reaction equation
[C:1]([NH:6][C:7]1[NH:8][C:9](=[O:34])[C:10]2[N:11]=[CH:12][N:13]([C:32]=2[N:33]=1)[C@@H:14]1[O:31][C@H:21]([CH2:22][O:23][Si:24]([C:27]([CH3:30])([CH3:29])[CH3:28])([CH3:26])[CH3:25])[C@@H:16]([O:17][CH2:18][S:19][CH3:20])[CH2:15]1)(=[O:5])[CH:2]([CH3:4])[CH3:3].[C:35]1([N:41]([C:45]2[CH:50]=[CH:49][CH:48]=[CH:47][CH:46]=2)[C:42](Cl)=[O:43])[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1.C(N(CC)C(C)C)(C)C>N1C=CC=CC=1>[C:1]([NH:6][C:7]1[N:8]=[C:9]([O:34][C:42](=[O:43])[N:41]([C:45]2[CH:46]=[CH:47][CH:48]=[CH:49][CH:50]=2)[C:35]2[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=2)[C:10]2[N:11]=[CH:12][N:13]([C:32]=2[N:33]=1)[C@@H:14]1[O:31][C@H:21]([CH2:22][O:23][Si:24]([C:27]([CH3:29])([CH3:28])[CH3:30])([CH3:25])[CH3:26])[C@@H:16]([O:17][CH2:18][S:19][CH3:20])[CH2:15]1)(=[O:5])[CH:2]([CH3:4])[CH3:3]

Participants

5

Reactant 3

HCID 65741N,N-Diphenylcarbamic chlorideHCID 81531DiisopropylethylamineHCID 136404885N2-isobutyryl-3'-O-(methylthiomethyl)-5'-O-(tert-butyldimethylsilyl)-2'-deoxyguanosine

Product 1

HCID 86638828N2-isobutyryl-O6-diphenylcarbamoyl-3'-O-(methylthiomethyl)-5'-O-(tert-butyldimethylsilyl)-2'-deoxyguanosineYield 80%

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Procedure

To 1.0 g N2-isobutyryl-3′-O-(methylthimethyl)-5′-O-(tert-butyldimethylsilyl)-2′-deoxyguanosine (11, 1.95 mmol) dissolved in 22 mL dry pyridine were added diphenylcarbamoyl chloride (0.677 g, 2.92 mmol) and 1.02 mL N,N-diisopropylethylamine, and stirred at room temperature for 3 h under nitrogen atmosphere. The reaction mixture became dark red during this time. The solvent was removed under high vacuum, and product was then purified by silica gel column chromatography using EtOAc:hex/1:1 to 7:3 as mobile phase. The product 12 was isolated as yellowish powder (1.09 g, ˜80% yield; Rf=0.7, EtOAc:hex (1:1)). HR-MS: Obs. m/z 707.3068 calcd. for C35H47O6N6SiS 707.3047 [M+H]+. 1H-NMR (CDCl3): δH 8.25 (s, 1H), 7.94 (brs, 1H), 7.47-7.37 (m, 10H), 6.42 (m, 1H), 4.75 (m, 2H), 4.71 (m, 1H), 4.18 (m, 1H), 3.88-3.70 (m, 2H), 2.80 (m, 1H), 2.60 (m, 1H), 2.19 (s, 3H), 1.30 (d, J=7.2 Hz, 6H), 0.93 (s, 9H) and 0.14 (s, 6H) ppm.

Workup

  1. customThe solvent was removed under high vacuum, and product
  2. customwas then purified by silica gel column chromatography

Sources & evidence

ORD record
ord-0eef73ecf2e6425296a94f969e3c9f64
Source dataset
uspto-grants-2016_09
Patent number
US09434989B2

Linked notes

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