تفاعل #65047

ord-7c6634747e7c46b5bdc7b005be1b4622

المذيبات

ظروف التفاعل

الظروف التفصيلية
See reaction.notes.procedure_details.

المعالجة

  1. 1
    أخرىconsumption of the active ester and formation of N-[4-[2-[2-Amino-4,7-dihydro-4-oxo-3H-pyrrolo[2,3-d]pyrimidin-5-yl]ethyl]benzoyl]glutamic acid dimethyl ester
  2. 2
    ترشيحThe reaction mixture was filtered
  3. 3
    تركيزthe above product concentrated
  4. 4
    أخرىpurified by silica chromatography (elution 1:4 methanol:methylene chloride)

الإجراء التجريبي

To 2.00 g (6.74 mmol) of 4-[2-(2-amino-4,7-dihydro-4-oxo-3H-pyrrolo[2,3-d]pyrimidin-5-yl)ethyl]benzoic acid, prepared in Preparation 4, in 23 ml dimethylformamide under nitrogen was added 1.40 g (13.8 mmol) of N-methylmorpholine and 1.17 g (6.70 mmol) of 4-chloro-2,6-dimethoxytriazine. The formation of the active ester was monitored by the HPLC analysis of aliquots. After 40 minutes at room temperature 0.70 g (6.9 mmol) of N-methylmorpholine was added followed by 1.56 g (7.37 mmol) L-glutamic acid dimethyl ester hydrochloride. After 30 minutes HPLC analysis indicated substantially complete consumption of the active ester and formation of N-[4-[2-[2-Amino-4,7-dihydro-4-oxo-3H-pyrrolo[2,3-d]pyrimidin-5-yl]ethyl]benzoyl]glutamic acid dimethyl ester. The reaction mixture was filtered and the above product concentrated and purified by silica chromatography (elution 1:4 methanol:methylene chloride). The pure fractions were pooled and provided 1.30 g of the above product in a yield of 43 percent. 1H NMR (DMSO-d6) δ2.01 (m, 2H), 2.40 (t, J= 7.4 Hz, 2H), 2.80 (m, 2H), 2.92 (m, 2H), 3.53 (s, 3H), 3.59 (s, 3H), 4.40 (m, 1H), 5.99 (s, 2H), 6.26 (d, J=1.9 Hz, 1H), 7.23 (d, J=8.2 Hz, 2H), 7.73 (d, J=8.2 Hz, 2H), 8.62 (d, J=7.5 Hz, 1H), 10.15 (s, 1H), 10.57 (d, J=1.9 Hz, 1H).

المصدر

DOI: 10.6084/m9.figshare.5104873.v1براءة الاختراع: US05416211uspto-grants-1995_05