1-Bromononane → (2R,3R,4R,5R)-5-(2,6-Diamino-9H-purin-9-yl)-2-(hydroxymethyl)-4-(nonyloxy)tetrahydrofuran-3-ol
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]=1Participants
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
- customto yield 83 g of crude product
- custom50 g of crude product was purified by silica gel chromatography
- additionFraction containing 2′-O-nonyl and 3′-O-nonyl product
Sources & evidence
- ORD record
- ord-d4d6fe96105244f6bdd11f014c8e0824
- Source dataset
- uspto-grants-2001_06
- Patent number
- US06242592B1
Reaction notes
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