Triphenylphosphine → 8-(6-Bromo-benzo[1,3]dioxol-5-ylsulfanyl)-9-(3-bromo-propyl)adenine

HRID 2369238Notes

Reaction equation

HRID 2369238 reaction equation
[Br:1][C:2]1[C:3]([S:11][C:12]2[NH:20][C:19]3[C:14](=[N:15][CH:16]=[N:17][C:18]=3[NH2:21])[N:13]=2)=[CH:4][C:5]2[O:9][CH2:8][O:7][C:6]=2[CH:10]=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.[Br:41][CH2:42][CH2:43][CH2:44]O.C1C=CC(COC(/N=N/C(OCC2C=CC=CC=2)=O)=O)=CC=1>C1(C)C=CC=CC=1.C(Cl)Cl.C(O)(C)C.CCOC(C)=O.C(Cl)(Cl)Cl>[Br:1][C:2]1[C:3]([S:11][C:12]2[N:13]([CH2:44][CH2:43][CH2:42][Br:41])[C:14]3[C:19]([N:20]=2)=[C:18]([NH2:21])[N:17]=[CH:16][N:15]=3)=[CH:4][C:5]2[O:9][CH2:8][O:7][C:6]=2[CH:10]=1

Participants

10

Reactant 4

HCID 11776TriphenylphosphineHCID 123083-Bromo-1-propanolHCID 5387121Dibenzyl azodicarboxylateHCID 114740228-(6-Bromo-benzo[1,3]dioxol-5-ylsulfanyl)adenine

Product 1

HCID 115187478-(6-Bromo-benzo[1,3]dioxol-5-ylsulfanyl)-9-(3-bromo-propyl)adenineYield 21%

Reagents, catalysts & solvents 5

HCID 1140TolueneSolventHCID 3776IsopropanolSolventHCID 6212ChloroformSolvent2×HCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

A solution of 8-(6-Bromo-benzo[1,3]dioxol-5-ylsulfanyl)adenine (513 mg, 1.4 mmol), PPh3 (808 mg, 3.08 mmol), 3-bromo-1-propanol (253 mg, 165 L, 1.82 mmol), DBAD (1612 mg, 7 mmol) in toluene (43.8 mL) and CH2Cl2 (8.75, mL) was stirred at room temperature for 20 min. The reaction mixture was loaded to a silica gel column (CHCl3 then CHCl3:EtOAc:hexanes:i-Propanol at 4:4:2:1) to provide the 9N-alkylated compound, 8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-9-(3-bromo-propyl)adenine) (142.6 mg, 21% yield). A solution of this product (142.6 mg, 0.29 mmol) in 1,4-dioxane (12 mL) and i-propylamine (3 mL) was stirred at 100° C. for 2.5 h. The solvent was removed under vacuum and the crude purified by preparatory thin layer chromatography on silica gel (CHCl3:MeOH:NH4OH at 10:1:0.5 then EtOAc:CH2Cl2:MeOH at 2:2:1) to afford 12 (51 mg, 8% yield). 1H NMR (400 MHz, CDCl3) 8.30 (s, 1H), 7.04 (s, 1H), 6.81 (s, 1H), 6.48 (bs, 2H), 5.94 (s, 2H), 4.29 (t, J=7.0 Hz, 2H,), 2.74-2.68 (m, 1H), 2.57 (t, J=6.8 Hz, 2H), 2.02-1.95 (m, 2H), 1.02 (d, J=6.0 Hz, 6H). 13C NMR (100 MHz, CDCl3) 154.8, 152.9, 151.5, 148.8, 148.0, 145.2, 123.8, 120.0, 116.7, 113.2, 112.2, 102.3, 48.6, 43.8, 41.7, 30.2, 22.8; MS m/z 465.0 (M+H)+. HPLC: (a) 99.1% (65% water-35% acetonitrile); (b) 98.0% (20% to 40% acetonitrile).

Sources & evidence

ORD record
ord-eff6d8106cde416893b2f85a67cab279
Source dataset
uspto-grants-2014_04
Patent number
US08703942B2

Reaction notes

Loading…