Bromotrimethylsilane → 9-[1-Hydroxy-4-(phosphonomethoxy)but-2-oxy]guanine

HRID 345088Notes

Reaction equation

C([O:3][P:4]([CH2:9][O:10][CH2:11][CH2:12][CH:13]([O:16][N:17]1[CH:25]=[N:24][C:23]2[C:22](=[O:26])[NH:21][C:20]([NH2:27])=[N:19][C:18]1=2)[CH2:14][OH:15])([O:6]CC)=[O:5])C.Br[Si](C)(C)C>CN(C)C=O>[OH:15][CH2:14][CH:13]([O:16][N:17]1[CH:25]=[N:24][C:23]2[C:22](=[O:26])[NH:21][C:20]([NH2:27])=[N:19][C:18]1=2)[CH2:12][CH2:11][O:10][CH2:9][P:4]([OH:6])([OH:5])=[O:3]

Participants

Conditions

Temperature: 20 °C

Procedure

A solution of 9-[4-(diethoxyphosphorylmethoxy)-1-hydroxybut-2-oxy]guanine (95 mg, 0.23 mmol) in N,N-dimethylformamide (5 ml) was treated with bromotrimethylsilane (0.62 ml, 4.6 mmol) and stirred at 20° C. for 3 h. The reaction mixture was evaporated in vacuo, the residue dissolved in water and passed down reverse- phase silica eluting with water. Evaporation of the appropriate fractions in vacuo gave a white foamy solid which was recrystallised from acetone-water, affording 9-[1-hydroxy-4-(phosphonomethoxy)but-2-oxy]guanine (20 mg, 24%) as a white solid m.p. 188°-192° C. νmax (KBr) 3400, 3100, 1700, 1650 and 1600 cm-1 ; δH [(CD3)2SO] 1.85 (2H, m, HOCH2CHCH2), 3.30 (2H, br.s, D2O exchangeable, P(OH)2), 3.4-3.7 (6H,m, CH2OCH2P+CH2OH), 4.30 (1H, m, HOCH2CH), 5.0 (1H, br.s, D2O exchangeable, OH), 6.62 (2H, br.s, D2O exchangeable, NH2), 7.86 (1H, s, H-8); m/z (FAB+ve Ion), 372 (MNa+), 350 (MH+); Found: C, 33.97; H, 4.69; N, 20.11%; C10H16N5O7P requires C, 34.29; H, 4.62; N, 20.10%.

Workup

customThe reaction mixture was evaporated in vacuo
dissolutionthe residue dissolved in water
customEvaporation of the appropriate fractions in vacuo
customgave a white foamy solid which
customwas recrystallised from acetone-water

Sources & evidence

ORD record: ord-18e2817a75f74f849eac85bd93c43516
Source dataset: uspto-grants-1991_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US05055458

Reaction notes

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