ChemicalBook CAS DataBase List N6-Benzoyl-3'-deoxy-5'-O-(4,4'-dimethoxytrityl)-3'-fluoroadenosine

N6-Benzoyl-3'-deoxy-5'-O-(4,4'-dimethoxytrityl)-3'-fluoroadenosine synthesis

6synthesis methods

Product Name:N6-Benzoyl-3'-deoxy-5'-O-(4,4'-dimethoxytrityl)-3'-fluoroadenosine
CAS Number:170871-87-1
Molecular formula:C38H34FN5O6
Molecular Weight:675.72

Benzamide, N-[9-[5-O-[bis(4-methoxyphenyl)phenylmethyl]-2-O-[(1,1-dimethylethyl)dimethylsilyl]-β-D-xylofuranosyl]-9H-purin-6-yl]-

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N6-Benzoyl-3'-deoxy-5'-O-(4,4'-dimethoxytrityl)-3'-fluoroadenosine

170871-87-1
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Yield:170871-87-1 355 mg

Reaction Conditions:

Stage #1: N-(9-((2R,3R,4S,5R)-5-((bis(4-methoxyphenyl)(phenyl)methoxy)methyl)-3-((tert-butyldimethylsilyl)oxy)-4-hydroxytetrahydrofuran-2-yl)-9H-purin-6-yl)benzamidewith diethylamino-sulfur trifluoride in dichloromethane at -5 - 0; for 17 h;Inert atmosphere;
Stage #2: with tetrabutyl ammonium fluoride in tetrahydrofuran at -42; for 2.5 h;Inert atmosphere;

Steps:

1.5 Step 5: Preparation of N-(9-((2R,3S,4S,5R)-5-((bis(4- methoxyphenyl)(phenyl)methoxy)methyl)-4-fluoro-3-hydroxytetrahydrofuran-2-yl)-9H-purin-6-yl)benzamide (16):

The diastereomeric mixture of i5a and i5b (2.0 g, 2.53 mmol) was dissolved in anhydrous THF (100 mL) and cooled to -42°C under an inert nitrogen atmosphere before 1.0 M TBAF (3.80 mL, 3.80 mmol) was added. The reaction was stirred for 2.5 h, then quenched with saturated NaHCO3 (20 mL). The cold bath was removed, and the slurry was stirred for 10 minutes before the mixture was diluted with 5% brine (150 mL) and extracted with DCM (2 x 100 mL). The combined organic phases were dried (Na2SO4), with the drying agent filtered off, silica gel (4g) added to the filtrate and the solvent removed in vacuo. The crude material was purified by chromatography on silica gel (gradient elution 25-100% EtOAc/heptane) to give the desired compound 16 as a white solid: 355 mg; ‘H NMR (400 MHz, CDC13) 9.16 (s, 1H), 8.64 (s, 1H), 8.23 (s, 1H), 7.99 (d, J = 7.5 Hz, 2H), 7.59 (t, J = 7.4 Hz, 1H), 7.48 (t, J = 7.6 Hz, 2H), 7.41 - 7.31 (m, 3H), 7.31 -7.11 (m, 7H), 6.79 (d, J= 8.9 Hz, 4H), 6.16 (d, J= 7.3 Hz, 1H), 5.77 (br s, 1H), 5.27-5.10 (m, 2H), 4.53 (dt, J= 28.0 Hz, 3.4 Hz, 1H), 3.77 (s, 6H), 3.51 (dd, J = 10.7, 3.7 Hz, 1H), 3.34 (dd, J = 10.7, 3.3 Hz, 1H); ‘9F NMR (376.4 MHz, CDC13) - 197.5; ‘3C NMR (101 MHz, CDC13) 164.66, 158.64, 158.62, 152.60, 151.43, 149.34,144.22, 141.66, 135.29, 135.13, 133.40, 132.93, 129.96, 128.87, 127.99, 127.93, 127.86,127.07, 122.65, 113.26, 93.85, 92.02, 87.56 (d, J= 144 Hz), 83.56 (d, J= 23Hz), 77.30,74.63 (d, J = 16 Hz), 62.82 (d, J = 11 Hz), 55.26; LCMS (Method A) R 0.89 mm; mlz676.3 [M+Hj.

References:

WO2017/75477,2017,A1 Location in patent:Paragraph 00436; 00441

40615-36-9 Synthesis