Thionyl Chloride → HCID 14213641, compound
Reaction equation
[NH2:1][C:2]1[C:3]([C:11]#[N:12])=[N:4][C:5]([CH2:9]O)=[C:6]([Cl:8])[N:7]=1.S(Cl)([Cl:15])=O>>[NH2:1][C:2]1[C:3]([C:11]#[N:12])=[N:4][C:5]([CH2:9][Cl:15])=[C:6]([Cl:8])[N:7]=1Participants
Procedure
A suitable method of synthesizing 7-NR1R2 -MTX wherein either both R1 and R2 are hydrogen, or one is hydrogen and the other is C1 -C5 alkyl, is outlined in FIGS. 1A and 1B. A suitable method of synthesizing 7-NR1R2 -MTX wherein both R1 and R2 are hydrogen comprises (a) reacting phosphorus oxychloride with 3-amino-6-(chloromethyl)-2-pyrazinecarbonitrile 4-oxide (1) to yield 3-amino-5-chloro-6-(hydroxymethyl)-2-pyrazinecarbonitrile (2); (b) reacting 3-amino-5-chloro-6-(hydroxymethyl)-2-pyrazinecarbonitrile with thionyl chloride to form 3-amino-5-chloro-6-(chloromethyl)-2-pyrazinecarbonitrile (4); (c) reacting 3-amino-5-chloro-6-(chloromethyl)-2-pyrazinecarbonitrile with ethyl 4-methylaminobenzoate (3) to form ethyl 4-[N-(2-amino-3-cyano-6-chloro-5-pyrazinylmethyl)-N-methylamino]benzoate (5); (d) reacting ethyl 4-[N-(2-amino-3-cyano-6-chloro-5-pyrazinylmethyl)-N-methylamino]benzoate with guanidine to form 4-[N-(2,4-diamino-7-chloro-6-pteridinylmethyl)-N-methylamino]benzoate (6); (e) reacting 4-[N-(2,4-diamino-7-chloro-6-pteridinylmethyl)-N-methylamino]benzoate with ammonia to form 4-[N-(2,4,7-triamino-6-pteridinylmethyl)-N-methylamino]benzoic acid (7a); and (f) coupling 4-[N-(2,4,7-triamino-6-pteridinylmethyl)-N-methylamino]benzoic acid and diethyl L-glutamate hydrochloride.
Sources & evidence
- ORD record
- ord-1f863a8f660d4b64a57244c02908e10f
- Source dataset
- uspto-grants-1997_12
- Patent number
- US05698556
Reaction notes
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