Bromotrimethylsilane → 9-[3-(Phosphonomethoxy)propoxy]guanine

HRID 345074Notes

Reaction equation

Br[Si](C)(C)C.C([O:8][P:9]([CH2:14][O:15][CH2:16][CH2:17][CH2:18][O:19][N:20]1[CH:28]=[N:27][C:26]2[C:25](=[O:29])[NH:24][C:23]([NH2:30])=[N:22][C:21]1=2)([O:11]CC)=[O:10])C>CN(C)C=O>[P:9]([CH2:14][O:15][CH2:16][CH2:17][CH2:18][O:19][N:20]1[CH:28]=[N:27][C:26]2[C:25](=[O:29])[NH:24][C:23]([NH2:30])=[N:22][C:21]1=2)([OH:11])([OH:10])=[O:8]

Participants

Conditions

Temperature: 25 °C

Procedure

Bromotrimethylsilane (0.79 ml, 6 mmol) was added dropwise to a solution of 9-[3-(diethoxyphosphorylmethoxy)propoxy]guanine (0.38 g, 1 mmol) in dry N,N-dimethylformamide (4 ml) and the reaction stirred under nitrogen at 25° C. for 2 h. Concentration in vacuo, followed by co-evaporation three times with methanol gave an off-white solid which on recrystallisation from hot water gave 9-[3-(phosphonomethoxy)propoxy]guanine (267 mg, 83%) as a white crystalline solid; m.p. 247°-250° C.; νmax (KBr) 3320, 1693, 1646, 1370, 1250 cm-1 ; δH [(CD3)2SO] 1.90(2H, m, CH2CH2CH2), 3.57(2H, d, J8.5 Hz, CH2P), 3.67(2H, t, J6 Hz, CH2OCH2P), 4.32(2H, t, J6.6 Hz, NOCH2), 6.60(2H, br.s, D2O exchangeable, NH2), 7.95(1H, s, H-8), 10.63(1H, br.s, D2O exchangeable, NH); Found: C, 33.84; H, 4.60; N, 21.57%; C9H14N5O6P requires: C, 33.86; H, 4.42; N, 21.94%.

Workup

concentrationConcentration in vacuo
customgave an off-white solid which
customon recrystallisation from hot water

Sources & evidence

ORD record: ord-d09c0f0a196f43e9ae65381ce6188376
Source dataset: uspto-grants-1991_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US05055458

Reaction notes

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