Triethylamine → 6-[[3-Acetoxy-2-(diethoxyphosphorylmethoxy)propoxy]amino]-4-chloro-2,5-diformamidopyrimidine

HRID 6249Notes

Reaction equation

HRID 6249 reaction equation
Cl[C:2]1[C:7]([NH:8][CH:9]=[O:10])=[C:6]([Cl:11])[N:5]=[C:4]([NH:12][CH:13]=[O:14])[N:3]=1.[C:15]([O:18][CH2:19][CH:20]([CH2:31][O:32][NH2:33])[O:21][CH2:22][P:23](=[O:30])([O:27][CH2:28][CH3:29])[O:24][CH2:25][CH3:26])(=[O:17])[CH3:16].C(N(CC)CC)C>O1CCOCC1>[C:15]([O:18][CH2:19][CH:20]([O:21][CH2:22][P:23]([O:27][CH2:28][CH3:29])([O:24][CH2:25][CH3:26])=[O:30])[CH2:31][O:32][NH:33][C:2]1[N:3]=[C:4]([NH:12][CH:13]=[O:14])[N:5]=[C:6]([Cl:11])[C:7]=1[NH:8][CH:9]=[O:10])(=[O:17])[CH3:16]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 13989892N-(4,6-dichloro-2-formamido-pyrimidin-5-yl)formamideHCID 14862060Diethyl [2-acetoxy-1-(aminooxymethyl)ethoxy)methylphosphonate

Product 1

HCID 148620646-[[3-Acetoxy-2-(diethoxyphosphorylmethoxy)propoxy]amino]-4-chloro-2,5-diformamidopyrimidineYield 81.4%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
120 °C

Procedure

A mixture of 4,6-dichloro-2,5-diformamidopyrimidine (0.475 mg, 2 mmol), diethyl [2-acetoxy-1-(aminooxymethyl)ethoxy)methylphosphonate (0.60 mg, 2 mmol) and triethylamine (0.54 ml, 4 mmol) in dry dioxan (20 ml) was heated at 120° C. for 5 hours. The reaction mixture was cooled to ambient temperature, filtered, and the filtrate evaporated to leave a yellow oil. The oil was chromatographed on silica gel (eluant dichloromethane:methanol 97:3) to give the title compound as a pale yellow solid (0.81 g, 80%). 1H NMR: δH [(CD3)2SO] 1.23 (2×3H, 2×t, J=7 Hz, (OCH2CH3)2), 2.03 (3H,s, COCH3), 3.80-4.35 (11H,m, CH2CHCH2 +(OCH2CH3)2 +OCH2P), 8.16 (1H,br.s, sharpens to s. on D2O, CHO), 9.26 (1H,d,J=9.9 Hz. collapses to s. on D2O. CHO), 9.45 (1H,br.s, D2O exchangeable, NH), 10.8-10.95 (2H,m, D2O exchangeable 2×NH). Found: C,37.36; H,5.37; N,13.43%; C16H25N5O9PCl.H2O requires: C,37.18; H,5.27; N,13.55%. m/z: observed 497.1082; C16H25N5O9PCl(M+) requires 497.1078.

Workup

  1. temperatureThe reaction mixture was cooled to ambient temperature
  2. filtrationfiltered
  3. customthe filtrate evaporated
  4. customto leave a yellow oil
  5. customThe oil was chromatographed on silica gel (eluant dichloromethane:methanol 97:3)

Sources & evidence

ORD record
ord-5fc21e67a610459991f0bba4b51294ed
Source dataset
uspto-grants-1993_09
Patent number
US05247085

Reaction notes

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