N,N-Diphenylcarbamic chloride → 2',3',5'-tri-O-acetyl-6-O-(diphenylcarbamoyl)-2-N-methylguanosine

HRID 1810809Notes

Reaction equation

HRID 1810809 reaction equation
[C:1]([O:4][C@@H:5]1[C@H:9]([O:10][C:11](=[O:13])[CH3:12])[C@@H:8]([CH2:14][O:15][C:16](=[O:18])[CH3:17])[O:7][C@H:6]1[N:19]1[C:30]2[N:29]=[C:26]([NH:27][CH3:28])[NH:25][C:23](=[O:24])[C:22]=2[N:21]=[CH:20]1)(=[O:3])[CH3:2].[C:31]1([N:37]([C:41]2[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=2)[C:38](Cl)=[O:39])[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1.C(N(C(C)C)CC)(C)C>N1C=CC=CC=1>[C:1]([O:4][C@@H:5]1[C@H:9]([O:10][C:11](=[O:13])[CH3:12])[C@@H:8]([CH2:14][O:15][C:16](=[O:18])[CH3:17])[O:7][C@H:6]1[N:19]1[C:30]2[N:29]=[C:26]([NH:27][CH3:28])[N:25]=[C:23]([O:24][C:38](=[O:39])[N:37]([C:41]3[CH:42]=[CH:43][CH:44]=[CH:45][CH:46]=3)[C:31]3[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=3)[C:22]=2[N:21]=[CH:20]1)(=[O:3])[CH3:2]

Participants

5

Reactant 3

HCID 65741N,N-Diphenylcarbamic chlorideHCID 81531DiisopropylethylamineHCID 1354716042',3',5'-Tri-O-acetyl-2-N-methylguanosine

Product 1

HCID 668930642',3',5'-tri-O-acetyl-6-O-(diphenylcarbamoyl)-2-N-methylguanosineYield 55%

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Procedure

To a solution of 2′,3′,5′-tri-O-acetyl-2-N-methylguanosine 3 (3.0 g, 7.1 mmol, 1.0 eq) in dry pyridine (50 mL) were added diphenylcarbamoyl chloride (3.45 g, 15 mmol, 2.1 eq) and diisopropylethylamine (1.9 mL, 11.4 mmol, 1.6 eq). The dark brown reaction mixture was then stirred at room temperature for 1 h to obtain 2′,3′,5′-tri-O-acetyl-6-O-(diphenylcarbamoyl)-2-N-methylguanosine 4. TLC showed complete conversion at this stage of the reaction. The reaction mixture was then diluted with pyridine (15 mL) and EtOH (30 mL). To this solution cooled at 0° C. was added 2 M NaOH (25 mL), which was precooled at 0° C. The reaction mixture was stirred for 10 min at 0° C. Acetic acid (c.a. 5 mL) was then added to neutralize the solution. Extraction with CH2Cl2 followed by chromatography on silica gel afforded 5 in 55% yield (1.92 g). TLC (CH2Cl2:MeOH, 9:1 v/v): Rf=0.5; 1H NMR (DMSO-d6, 400 MHz) δ (ppm): 2.81 (d, 3H), 3.51-3.56 (m, 1H), 3.61-3.66 (m, 1H), 3.90 (m, 1H), 4.02 (q, 1H), 4.15 (br.d, 1H), 4.62 (br.s, 1H), 4.99 (br.s, 1H), 5.21 (d, J=4.8 Hz, 1H), 5.48 (d, J=5.6 Hz, 1H), 5.82 (d, J=5.6 Hz, 1H), 7.28-7.32 (m, 4H), 7.4-7.44 (m, 6H), 8.19 (s, 1H); 13C NMR (DMSO-d6, 400 MHz) δ (ppm): 28.3, 61.5, 70.5, 73.1, 85.5, 116.4, 127.1, 129.4, 140.9, 141.8, 150.4, 155.6, 155.9, 159.6; ESI-MS (ES+) calculated for C24H24N6O6 492.1757, found 493.2 (M+H+), 515.2 (2M+Na+), 1007.4 (2M+Na+).

Sources & evidence

ORD record
ord-9811cd64d4ee44e4b1f2493df5713418
Source dataset
uspto-grants-2013_01
Patent number
US08362203B2

Reaction notes

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