Methanol → 6-N-(4-Monomethoxytrityl)-9-(2-deoxy-5-O-(4-monomethoxytrityl)-beta-L-threopentofuranosyl)adenine

HRID 1005757Notes

Reaction equation

HRID 1005757 reaction equation
[CH3:1][O:2][C:3]1[CH:39]=[CH:38][C:6]([C:7]([NH:20][C:21]2[N:29]=[CH:28][N:27]=[C:26]3[C:22]=2[N:23]=[CH:24][N:25]3[C@H:30]2[O:35][C@@H:34]([CH2:36][OH:37])[C@@H:32]([OH:33])[CH2:31]2)([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=2)=[CH:5][CH:4]=1.[CH3:40][O:41][C:42]1[CH:61]=[CH:60][C:45]([C:46](Cl)([C:53]2[CH:58]=[CH:57][CH:56]=[CH:55][CH:54]=2)[C:47]2[CH:52]=[CH:51][CH:50]=[CH:49][CH:48]=2)=[CH:44][CH:43]=1.CO>N1C=CC=CC=1>[CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]([C:7]([NH:20][C:21]2[N:29]=[CH:28][N:27]=[C:26]3[C:22]=2[N:23]=[CH:24][N:25]3[C@H:30]2[O:35][C@@H:34]([CH2:36][O:37][C:46]([C:53]3[CH:58]=[CH:57][CH:56]=[CH:55][CH:54]=3)([C:47]3[CH:52]=[CH:51][CH:50]=[CH:49][CH:48]=3)[C:45]3[CH:44]=[CH:43][C:42]([O:41][CH3:40])=[CH:61][CH:60]=3)[C@@H:32]([OH:33])[CH2:31]2)([C:14]2[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=2)[C:8]2[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=2)=[CH:38][CH:39]=1

Participants

5

Reactant 3

HCID 887MethanolHCID 84462p-(Chlorodiphenylmethyl)anisoleHCID 120709966-N-(4-Monomethoxytrityl)-9-(2-deoxy-beta-L-threo-pentofuranosyl)adenine

Product 1

HCID 120709976-N-(4-Monomethoxytrityl)-9-(2-deoxy-5-O-(4-monomethoxytrityl)-beta-L-threopentofuranosyl)adenineYield 72%

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Procedure

Compound 6 (0.62 g, 1.24 mmol) in dry pyridine (25 mL) was treated with 4-monomethoxytrityl chloride (0.46 g, 1.49 mmol) at room temperature for 16 h. After addition of methanol (5 mL), the mixture was concentrated to dryness. The residue was dissolved in dichloromethane (60 mL) and washed successively with water (40 mL), a saturated aqueous solution of NaHCO3 (40 mL) and water (3×40 mL). The organic layer was dried, filtered, concentrated and co-evaporated with toluene and methanol. The residue was purified by silica gel column chromatography (0-10% MeOH in dichloromethane) to give 7 (0.71 g, 72%) as a foam: 1H NMR (DMSO-d6): δ 2.21 (d, 1H, H-2′ J2′,2″=14.3 Hz), 2.6-2.7 (m, 1H, H-2″), 3.1-3.3 (2m, 2H, H-5′ and H-5″), 3.64 and 3.65 (2s, 6H, 2×OCH3), 4.1-4.2 (m, 1H, H-4′), 4.2-4.3 (m, 1H, H-3′), 5.68 (d, 1H, OH-3′, JH,OH=5.2 Hz), 6.24 (d, 1H, H-1′, J1′,2″=7.0 Hz), 6.7-6.8 and 7.1-7.3 (2m, 29H, 2 MMTr and NH-6), 7.83 and 8.21 (2s, 2H, H-2 and H-8); ms: matrix G/T, (FAB+) m/z 796 [M+H]+, 408 [BH2]+, (FAB−) m/z 794 [M−H]−, 406 [B]−; UV (95% ethanol): λmax 275 nm (ε 30900), λmin 246 nm (ε 12800); [α]D20=+14 (c 1.03, DMSO).

Workup

  1. concentrationthe mixture was concentrated to dryness
  2. dissolutionThe residue was dissolved in dichloromethane (60 mL)
  3. washwashed successively with water (40 mL)
  4. customThe organic layer was dried
  5. filtrationfiltered
  6. concentrationconcentrated and co-evaporated with toluene and methanol
  7. customThe residue was purified by silica gel column chromatography (0-10% MeOH in dichloromethane)

Sources & evidence

ORD record
ord-c69cac4598e94eadb0a38c435baceef4
Source dataset
uspto-grants-2004_09
Patent number
US06787526B1

Reaction notes

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