Ammonia → HCID 22877221, compound

HRID 1379634Notes

Reaction equation

HRID 1379634 reaction equation
O(CC(N)C)C1C=CC=CC=1.C(O[C@@H]1[C@H](OC(=O)C)[C@@H](COC(=O)C)O[C@H]1N1C=NC2C1=NC(N)=NC=2Cl)(=O)C.C(N(CC)CC)C.C(N(C(C)C)CC)(C)C.C([O:60][C@@H:61]1[C@H:65]([O:66]C(=O)C)[C@@H:64]([CH2:70][O:71]C(=O)C)[O:63][C@H:62]1[N:75]1[C:94]2[N:93]=[C:92]([NH2:95])[N:91]=[C:79]([NH:80][CH:81]([CH3:90])[CH2:82][O:83][C:84]3[CH:89]=[CH:88][CH:87]=[CH:86][CH:85]=3)[C:78]=2[N:77]=[CH:76]1)(=O)C.N>O1CCOCC1>[NH2:95][C:92]1[N:91]=[C:79]([NH:80][CH:81]([CH3:90])[CH2:82][O:83][C:84]2[CH:89]=[CH:88][CH:87]=[CH:86][CH:85]=2)[C:78]2[N:77]=[CH:76][N:75]([C:94]=2[N:93]=1)[C@@H:62]1[O:63][C@H:64]([CH2:70][OH:71])[C@@H:65]([OH:66])[C@H:61]1[OH:60]

Participants

8

Reactant 6

HCID 222AmmoniaHCID 8471TriethylamineHCID 370871-Phenoxy-2-propanamineHCID 81531DiisopropylethylamineHCID 10788628(2R,3R,4R,5R)-2-(Acetoxymethyl)-5-(2-amino-6-chloro-9H-purin-9-yl)tetrahydrofuran-3,4-diyl diacetateHCID 22877234HCID 22877234, compound

Product 1

HCID 22877221HCID 22877221, compoundYield 33%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

1-Phenoxy-2-propylamine (2.90 g, 19.2 mmol) and 9-(2,3,5-tri- O-acetyl-β-D-ribofuranosyl)-2-amino-6-chloro-9H-purine (6.94 g, 16.2 mmol) were dissolved in dioxan (50 ml) and triethylamine (4.5 ml, 33.2 mmol) was introduced. After stirring the reaction mixture for 18 h at room temperature, diisopropylethylamine (2.08 g, 16.1 mmol) was added and the solution was heated at 80° C. for 100 h. Following column column chromatography, a 1.3 g sample of the resultant 2',3',5'-tri- O-acetyl-2-amino- N-(1-phenoxy-2-propyl)adenosine was deprotected using saturated methanolic ammonia (50 ml). The reaction mixture was evaporated, and the residue dissolved in in a mixture of ethyl acetate (150 ml) and water (150 ml). The phases were separated and the ethyl acetate phase was washed with water (2×150 ml). The ethyl acetate phase was then extracted with pH 2 dilute hydrochloric acid, and this acidic aqueous phase was washed with ethyl acetate (2×100 ml), and basified with sodium bicarbonate solution before extraction with ethyl acetate (100 ml). The ethyl acetate phase was was dried (MgSO4) and evaporated to give the title compound (0.43 g, 33%) a mixture of diastereoisomers as an amorphous foam, 1H NMR (DMSO-d6)δ 1.28 (3H, d, --CH3), 3.49-3.57 (1H, m, H-5'a), 3.61-3.68 (1H, m, H-5'b), 3.85-3.94 and 4.07-4.15 (4H, 2m, m, H-4', H-3' and --CH2 --), 4.50 (1H, q, H-2'), 4.68 (1H, br, --C HCH3), 5.11, 5.36 (2H, 2d, 2'- and 3'-OH), 5.40 (1H, t, 5'-OH) 5.73 (1H, d, H-1'), 5.83 (1H, br, --NH2), 6.88-6.96 (3H, m, Ar--H), 7.22-7.31 (2H, t, Ar--H), 7.95 (1H, s, H-8).

Workup

  1. temperaturethe solution was heated at 80° C. for 100 h
  2. customThe reaction mixture was evaporated
  3. dissolutionthe residue dissolved in in a mixture of ethyl acetate (150 ml) and water (150 ml)
  4. customThe phases were separated
  5. washthe ethyl acetate phase was washed with water (2×150 ml)
  6. extractionThe ethyl acetate phase was then extracted with pH 2 dilute hydrochloric acid
  7. washthis acidic aqueous phase was washed with ethyl acetate (2×100 ml)
  8. extractionbasified with sodium bicarbonate solution before extraction with ethyl acetate (100 ml)
  9. dry with materialThe ethyl acetate phase was was dried (MgSO4)
  10. customevaporated

Sources & evidence

ORD record
ord-bf064a161dea4f6e82e9fb251a01a114
Source dataset
uspto-grants-1997_09
Patent number
US05672588

Reaction notes

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