Methylhydrazine → 3'-O-Amino-5'-O-(t-Butyldimethylsilyl)thymidine

HRID 54633Notes

Reaction equation

HRID 54633 reaction equation
CNN.[Si:4]([O:11][CH2:12][C@H:13]1[O:17][C@@H:16]([N:18]2[CH:26]=[C:24]([CH3:25])[C:22](=[O:23])[NH:21][C:19]2=[O:20])[CH2:15][C@@H:14]1[O:27][N:28]1C(=O)C2=CC=CC=C2C1=O)([C:7]([CH3:10])([CH3:9])[CH3:8])([CH3:6])[CH3:5]>C(Cl)Cl>[NH2:28][O:27][C@@H:14]1[C@@H:13]([CH2:12][O:11][Si:4]([C:7]([CH3:10])([CH3:8])[CH3:9])([CH3:5])[CH3:6])[O:17][C@@H:16]([N:18]2[CH:26]=[C:24]([CH3:25])[C:22](=[O:23])[NH:21][C:19]2=[O:20])[CH2:15]1

Participants

4

Reactant 2

HCID 6061MethylhydrazineHCID 186587155'-O-(t-Butyldimethylsilyl)-3'-O-Phthalimidothymidine

Product 1

HCID 186587053'-O-Amino-5'-O-(t-Butyldimethylsilyl)thymidineYield 100%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Cold methylhydrazine (1.6 ml, 30 mmol) was added to a stirred solution of 5'-O-(t-butyldimethylsilyl)-3'-O-phthalimidothymidine (2, 4.6 g, 9.18 mmol) in dry CH2Cl2 (60 ml) at 5°-10° C. After 10 minutes white precipitation of 1,2-dihydro-4-hydroxy-2-methyl-1-oxophthalizine occurred. The suspension was stirred at room temperature for 1 h. The suspension was filtered and precipitate washed with CH2Cl2 (2×20 ml). The combined filtrates were concentrated and the residue purified by silica gel column chromatography. Elution with CH2Cl2 :MeOH (100:0→97:3, v/v) furnished the title compound (3.40 g, 100%) as white solid. Crystallization from CH2Cl2 gave white needles, m.p. 171° C.; 1H NMR (CDCl3) δ0.05 [s, 6, (CH3)2 ], 0.90 [s, 9, (CH3)3 ], 2.22-2.58 (2m, 2, 2'CH2), 3.9-4.08 (m, 3, 5'CH2, and 3'H) 4.30 (m, 1, 4H) 5.5 (br s, 2, NH2) 6.2 (m, 1, 1'H) 7.45 (s, 1, C6H) 8.9 (br s, 1, NH).

Workup

  1. customAfter 10 minutes white precipitation of 1,2-dihydro-4-hydroxy-2-methyl-1-oxophthalizine
  2. filtrationThe suspension was filtered
  3. washprecipitate washed with CH2Cl2 (2×20 ml)
  4. concentrationThe combined filtrates were concentrated
  5. customthe residue purified by silica gel column chromatography
  6. washElution with CH2Cl2 :MeOH (100:0→97:3

Sources & evidence

ORD record
ord-1bfefbd90e5a46f8bac1d0daa3759881
Source dataset
uspto-grants-1997_04
Patent number
US05623070

Reaction notes

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