Diisopropylethylamine → (2R,3R,4S,5R)-2-[2-Chloro-6-((R)-1-methyl-2-phenoxy-ethylamino)-purin-9-yl]-5-hydroxymethyl-tetrahydro-furan-3,4-diol

HRID 1379630Notes

Reaction equation

HRID 1379630 reaction equation
[O:1]([CH2:8][C@H:9]([NH2:11])[CH3:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C([O:20][C@@H:21]1[C@H:25]([O:26]C(=O)C2C=CC=CC=2)[C@@H:24]([CH2:35][O:36]C(=O)C2C=CC=CC=2)[O:23][C@H:22]1[N:45]1[CH:53]=[N:52][C:51]2[C:46]1=[N:47][C:48]([Cl:55])=[N:49][C:50]=2Cl)(=O)C1C=CC=CC=1.C(N(C(C)C)CC)(C)C>O1CCOCC1>[Cl:55][C:48]1[N:49]=[C:50]([NH:11][C@H:9]([CH3:10])[CH2:8][O:1][C:2]2[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=2)[C:51]2[N:52]=[CH:53][N:45]([C:46]=2[N:47]=1)[C@@H:22]1[O:23][C@H:24]([CH2:35][OH:36])[C@@H:25]([OH:26])[C@H:21]1[OH:20]

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 5324633(2R)-1-Phenoxy-2-propanamineHCID 116930649-(2,3,5-tri-O-benzoyl-beta-D-ribofuranosyl)-2,6-dichloro-9H-purine

Product 1

HCID 9845859(2R,3R,4S,5R)-2-[2-Chloro-6-((R)-1-methyl-2-phenoxy-ethylamino)-purin-9-yl]-5-hydroxymethyl-tetrahydro-furan-3,4-diolYield 64%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

(R)-1-phenoxy-2-propylamine (4.3 g, 23 mmol) was reacted with 9-(2,3,5-tri- O-benzoyl-β-D-ribofuranosyl)-2,6-dichloro-9H-purine (11.2 g, 18 mmol) in dioxan (150 ml) in the presence of diisopropylethylamine (5.3 g, 41 mmol). The reaction mixture was stirred at room temperature for 18 h, heated at 50° C. for 4 h, and stirred at room temperature for 60 h before being filtered and evaporated. The product (after purification by flash chromatography) was debenzoylated with methanolic ammonia to provide the title 2-chloro- N-[(R)-1-phenoxy-2-propyl]adenosine (after column chromatography) as a foam (4.2 g, 64%), 1H NMR (DMSO-d6)δ 1.31 (3H, d, --CH3), 3.52-3.59 (1H, m, H-5'a), 3.63-3.72 (1H, m, H-5'b), 3.92-3.99 and 4.10-4.21 (4H, 2 m, H-3', H-4' and --CH2 --), 4.52 (1H, dd, H-2'), 4.65 (1H, m, --CH3C H--), 5.07 (1H, t, 5'-OH), 5.22, 5.49 (2H, 2d, 2' and 3'-OH), 5.84 (1H, d, H-1 '), 6.88-7.02 (3H, m, Ar--H), 7.24-7.33 (2H, dd, Ar--H), 8.32-8.45 (2H, s & m, H-8 and N--H).

Workup

  1. temperatureheated at 50° C. for 4 h
  2. stirringstirred at room temperature for 60 h
  3. filtrationbefore being filtered
  4. customevaporated
  5. customThe product (after purification by flash chromatography)

Sources & evidence

ORD record
ord-9acb8c31339542e98ad1863d5812a52c
Source dataset
uspto-grants-1997_09
Patent number
US05672588

Reaction notes

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