1-Bromononane → (2R,3R,4R,5R)-5-(2,6-Diamino-9H-purin-9-yl)-2-(hydroxymethyl)-4-(nonyloxy)tetrahydrofuran-3-ol

HRID 2212479Notes

Reaction equation

HRID 2212479 reaction equation
[NH2:1][C:2]1[N:10]=[C:9]2[C:5]([N:6]=[CH:7][N:8]2[C@@H:11]2[O:17][C@H:16]([CH2:18][OH:19])[C@@H:14]([OH:15])[C@H:12]2[OH:13])=[C:4]([NH2:20])[N:3]=1.[H-].[Na+].Br[CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH3:32]>CN(C=O)C>[NH2:1][C:2]1[N:10]=[C:9]2[C:5]([N:6]=[CH:7][N:8]2[C@@H:11]2[O:17][C@H:16]([CH2:18][OH:19])[C@@H:14]([OH:15])[C@H:12]2[O:13][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH3:32])=[C:4]([NH2:20])[N:3]=1

Participants

5

Reactant 3

HCID 127421-BromononaneHCID 24758Sodium hydride2×HCID 722002-Aminoadenosine

Product 1

HCID 15858694(2R,3R,4R,5R)-5-(2,6-Diamino-9H-purin-9-yl)-2-(hydroxymethyl)-4-(nonyloxy)tetrahydrofuran-3-olYield 39.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

2,6-Diamino-9-(β-D-ribofuranosyl)purine (50 g, 180 mmol) was treated with sodium hydride (8.8 g, 220 mmol) and bromononane (59 g, 54.4 ml, 285 mmol) in DMF (700 ml) as per the procedure of Example 2 (the diamino compound in DMF was cooled in an ice bath during the addition of NaH) to yield 83 g of crude product. 50 g of crude product was purified by silica gel chromatography. Fraction containing 2′-O-nonyl and 3′-O-nonyl product were combined to give a 77:23 mixture (29 g) of the 2′ and 3′ product. Pure 2′-O-nonyl product is obtained by chromatography. 1H NMR (DMSO-d6) δ 0.95 (t, 3, CH3); 1.17 [m, 12, O—CH2—CH2—(CH2)6; 1.42 [m, 2, O—CH2CH2(CH2)6]; 3.27-3.70 (m, 2, H-5′); 3.50-3.70 [m, 2, O—CH2(CH2)7]; 3.95 (m, 1, H-4′), 4.24 (m, 1, H-3′); 4.40 (m, 1, H-2′); 5.10 (d, 1, 3′-OH, J=5 Hz); 5.50 (t, 1, 5′-OH, J=6 Hz); 5.76 (s, 2, 2-NH2); 5.83 (d, 1, H-1′, J=6.0 Hz); 6.81 (s, 2, 6-NH2); and 7.96 (s, 1, 8-H).

Workup

  1. customto yield 83 g of crude product
  2. custom50 g of crude product was purified by silica gel chromatography
  3. additionFraction containing 2′-O-nonyl and 3′-O-nonyl product

Sources & evidence

ORD record
ord-783094e498964291a572d92a04527ff6
Source dataset
uspto-grants-2006_09
Patent number
US07101993B1

Reaction notes

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