Diisopropylethylamine → 4-Chloro-6-[[4-(diethoxyphosphoryl)butoxy]amino]-2,5-diformamidopyrimidine

HRID 373878Notes

Reaction equation

HRID 373878 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.[NH2:15][O:16][CH2:17][CH2:18][CH2:19][CH2:20][P:21](=[O:28])([O:25][CH2:26][CH3:27])[O:22][CH2:23][CH3:24].C(N(CC)C(C)C)(C)C>COCCOCCOC>[Cl:11][C:6]1[C:7]([NH:8][CH:9]=[O:10])=[C:2]([NH:15][O:16][CH2:17][CH2:18][CH2:19][CH2:20][P:21]([O:22][CH2:23][CH3:24])([O:25][CH2:26][CH3:27])=[O:28])[N:3]=[C:4]([NH:12][CH:13]=[O:14])[N:5]=1

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 13989892N-(4,6-dichloro-2-formamido-pyrimidin-5-yl)formamideHCID 19808619Diethyl 4-(aminooxy)butylphosphonate

Product 1

HCID 198086554-Chloro-6-[[4-(diethoxyphosphoryl)butoxy]amino]-2,5-diformamidopyrimidineYield 83.7%

Reagents, catalysts & solvents 1

HCID 8150DiglymeSolvent

Conditions

Temperature
100 °C

Procedure

4,6-Dichloro-2,5-diformamidopyrimidine (0.35 g, 1.5 mmol), diethyl 4-(aminooxy)butylphosphonate (0.216 g, 0.93 mmol) and N,N-diisopropylethylamine (0.521 ml, 3 mmol) were dissolved in diglyme (15 ml) and stirred at 100° C. for 3 hr. The reaction mixture was then allowed to cool, the hydrochloride of N,N-diisopropylethylamine was filtered off and the filtrate was diluted with chloroform (150 ml). The resulting solution was washed with 4% aq. NaHCO3 (1×20 ml) and water (1×20 ml). The combined aqueous layers were extracted with chloroform (4×20 ml) and the combined chloroform solutions were evaporated to dryness. The residue was chromatographed on silica gel (eluted with chloroform-ethanol, 96:4) to yield the title compound (0.330 g, 81%). 1H NMR: δH ((CD3)2SO) 1.22 (6H, t, J=7Hz, (OCH2CH3)2), 1.7 (6H, m, CH2CH2CH 2 P), 3.87 (2H, t, J=5Hz, OCH2), 3.98 (4H, m, (OCH2CH3)2) 8.14 (1H, s, 5-NHCHO), 8.31 (1H, s, 6-NHCHO), 9.24 (1H, br.s, 2-NHCHO), 9.41 (1H, br.s, D2O exchangeable, NHOCH2), 10.81 (2H, br.s, D2O exchangeable, NHCHO, NHCHO).

Workup

  1. temperatureto cool
  2. filtrationthe hydrochloride of N,N-diisopropylethylamine was filtered off
  3. additionthe filtrate was diluted with chloroform (150 ml)
  4. washThe resulting solution was washed with 4% aq. NaHCO3 (1×20 ml) and water (1×20 ml)
  5. extractionThe combined aqueous layers were extracted with chloroform (4×20 ml)
  6. customthe combined chloroform solutions were evaporated to dryness
  7. customThe residue was chromatographed on silica gel (eluted with chloroform-ethanol, 96:4)

Sources & evidence

ORD record
ord-7097dfc27a494542b54f4f8b44000ce7
Source dataset
uspto-grants-1992_11
Patent number
US05166198

Reaction notes

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