反应详情

A mixture of the product described in the preceding paragraph (a) (2.55 g, 0.005 mol), formamidine acetate (Aldrich, 2.08 g, 0.02 mol), and 2-ethoxyethanol (30 mL) was refluxed for 45 min, the solvent was evaporated under reduced pressure, and the dark residue was partitioned between CHCl3 and H2O. The emulsion was allowed to settle, and the residue after evaporation of the CHCl3 layer was passed through a silica gel column (70 g, 3×35 cm), which was eluted first with 19:1 CHCl3 --MeOH to sequentially remove a brown impurity and yellow impurity, and then with 15:1 CHCl3 --MeOH to obtain the product. TLC homogeneous fractions (Rf 0.5, Analab silica gel plates, 9:1 CHCl3 --MeOH) were combined, care being taken to exclude a colored impurity immediately following the product, and the solvent was evaporated to obtain 2-desaminoaminopterin as a tan powder (1.33 g, 58% yield); mp 103°-110° C., with sintering at lower temp; IR (KBr) 3370, 2980, 2940, 1730 (ester C=O), 1635, 1610, 1565, 1555, 1515, 1455, 1420, 1395, 1370, 1325, 1310, 1265 cm-1; UV: λ max (95% EtOH) 248 nm (ε18,200), 289 (23,000), 338 (7,390); NMR (CDCl3 δ1.40, (s, γ-t-OBu, 1.47 (s, α-t-OBu), 2.32 (m, CH2CH2, 4.70 (m, CH2NH), 5.58 (m, α-CH), 6.60 (d, J=8 Hz, 3'- and 5'-H), 6.8-7.3 (m, 4--NH2 and CONH), 7.67 (d, J=8 Hz, 2'- and 4'-H), 8.73 (s, 2--H), 9.05 (s, 7--H). Anal. (C27H35N7O5.0.25H2O) Calcd: C, 59.82; H, 6.60; N, 18.09. Found: C, 59.74; H, 6.54; N, 17.90. Acidolysis of this di-tert-butyl ester product was carried out as follows to provide 2-desamino-aminopterin having the structural formula given above in which R1 and R2 are both hydrogen.

1. additionA mixture of the product
2. temperaturewas refluxed for 45 min
3. customthe solvent was evaporated under reduced pressure
4. customthe dark residue was partitioned between CHCl3 and H2O
5. customthe residue after evaporation of the CHCl3 layer
6. washwas eluted first with 19:1 CHCl3
7. customMeOH to sequentially remove a brown impurity and yellow impurity
8. customwith 15:1 CHCl3 --MeOH to obtain the product
9. customthe solvent was evaporated