Claims for Patent: 9,254,341

Summary for Patent: 9,254,341

Title:	Methods of manufacture of pteroyl-amino acid-fluorescent dyes
Abstract:	The present invention discloses a process for preparing a compound having the formula ##STR00001## Including Reacting a compound of the formula 1: ##STR00002## with a compound of the formula: ##STR00003## in the presence of a polar solvent and trifluoroacetic acid to provide a compound of the formula: ##STR00004## or a racemic mixture thereof; and further reacting the compound of the formula: ##STR00005## or a racemic mixture thereof; with sodium hydroxide and a compound of the formula: ##STR00006## wherein R.sup.1 and R.sup.2 are as defined above.
Inventor(s):	Kularatne; Sumith A. (West Lafayette, IN), Gagare; Pravin (West Lafayette, IN), Noshi; Mohammad (West Lafayette, IN)
Assignee:
Application Number:	14/046,916
Patent Claims:	1. A method for synthesizing a compound of the formula: ##STR00051## or a racemic mixture thereof, wherein: X is selected from the group consisting of: ##STR00052## or a racemic mixture thereof; and Y is represented by the formula: ##STR00053## wherein: R.sup.1 is independently selected from the group consisting of O, S, NH, CH.sub.2 and CH.sub.2CH.sub.2; and R.sup.2 is independently selected from the group consisting of CH.sub.2 and CH.sub.2CH.sub.2; comprising the steps of: (a) reacting a compound of the formula 1: ##STR00054## with a compound of the formula: ##STR00055## or a racemic mixture thereof, in the presence of a polar solvent and trifluoroacetic acid to provide a compound of the formula: ##STR00056## or a racemic mixture thereof; (b) reacting the compound of the formula: ##STR00057## or a racemic mixture thereof; with sodium hydroxide and a dye compound of the formula: ##STR00058## wherein: R.sup.1 is independently selected from the group consisting of O, S, NH, CH.sub.2 and CH.sub.2CH.sub.2; and R.sup.2 is independently selected from the group consisting of CH.sub.2 and CH.sub.2CH.sub.2; and (c) isolating the compound of the formula: ##STR00059## or a racemic mixture thereof, wherein: R.sup.1 is independently selected from the group consisting of O, S, NH, CH.sub.2 and CH.sub.2CH.sub.2; and R.sup.2 is independently selected from the group consisting of CH.sub.2 and CH.sub.2CH.sub.2. 2. The method of claim 1, wherein the dye compound in step (b) is selected from the group consisting of: ##STR00060## 3. The method of claim 1, wherein the polar solvent is selected from the group consisting of dimethylformamide, dimethylsulfoxide and water. 4. A method for synthesizing a compound of the formula: ##STR00061## wherein: W, X, Y and Z are independently selected from the group consisting of H.sup.+, Na.sup.+, K.sup.+ or NH.sub.4.sup.+; comprising the steps of: (a) reacting a compound of the formula: ##STR00062## with a compound of the formula: ##STR00063## in the presence of dimethylformamide and trifluoroacetic acid to provide a compound of the formula: ##STR00064## wherein: W is independently selected from the group consisting of H.sup.+, Na.sup.+, K.sup.+ or NH.sub.4.sup.+; (b) reacting the compound of the formula: ##STR00065## with sodium hydroxide and a dye compound of the formula: ##STR00066## wherein: X, Y and Z are independently selected from the group consisting of H.sup.+, Na.sup.+, K.sup.+ or NH.sub.4.sup.+; and (c) isolating the compound of the formula: ##STR00067## wherein: W, X, Y and Z are independently selected from the group consisting of H.sup.+, Na.sup.+, K.sup.+ or NH.sub.4.sup.+. 5. A method for synthesizing an isotopic form of a compound of the formula: ##STR00068## wherein said isotopic form comprises one or more carbon and/or hydrogen isotopes selected from the group consisting of .sup.2H, .sup.3H, .sup.13C and .sup.14C, and further wherein: W, X, Y and Z are independently selected from the group consisting of H.sup.+, Na.sup.+, K.sup.+ or NH.sub.4.sup.+; comprising the steps of: (a) reacting a compound of the formula: ##STR00069## wherein: W is selected from the group consisting of H.sup.+, Na.sup.+, K.sup.+ or NH.sub.4.sup.+; with an isotopic form of a compound of the formula: ##STR00070## wherein said isotopic form comprises one or more carbon and/or hydrogen isotopes selected from the group consisting of .sup.2H, .sup.3H, .sup.13C and .sup.14C, and further wherein: W is selected from the group consisting of H.sup.+, Na.sup.+, K.sup.+ or NH.sub.4.sup.+; in the presence of dimethylformamide to provide an isotopic form of a compound of the formula: ##STR00071## wherein said isotopic form comprises one or more carbon and/or hydrogen isotopes selected from the group consisting of .sup.2H, .sup.3H, .sup.13C and .sup.14C, and further wherein: W is selected from the group consisting of H.sup.+, Na.sup.+, K.sup.+ or NH.sub.4.sup.+; (b) reacting the isotopic form of the compound of the formula: ##STR00072## wherein said isotopic form comprises one or more carbon and/or hydrogen isotopes selected from the group consisting of .sup.2H, .sup.3H, .sup.13C and .sup.14C, and further wherein: W is selected from the group consisting of H.sup.+, Na.sup.+, K.sup.+ or NH.sub.4.sup.+; with sodium hydroxide and a dye compound of the formula: ##STR00073## wherein X, Y and Z are independently selected from the group consisting of H.sup.+, Na.sup.+, K.sup.+ or NH.sub.4.sup.+; and (c) isolating the isotopic form of the compound of the formula: ##STR00074## wherein said isotopic form comprises one or more carbon and/or hydrogen isotopes selected from the group consisting of .sup.2H, .sup.3H, .sup.13C and .sup.14C, and further wherein: W, X, Y and Z are independently selected from the group consisting of H.sup.+, Na.sup.+, K.sup.+ or NH.sub.4.sup.+. 6. A method for the solid phase synthesis of a compound of the formula: ##STR00075## wherein: W, X, Y and Z are independently selected from the group consisting of H.sup.+, Na.sup.+, K.sup.+ or NH.sub.4.sup.+; comprising in a solid phase peptide synthesizer, the steps of: (a) reacting a compound of the formula: ##STR00076## wherein: W is selected from the group consisting of H.sup.+, Na.sup.+, K.sup.+ or NH.sub.4.sup.+; with a compound of the formula: ##STR00077## wherein: is a resin bead; in the presence of dimethylformamide to provide a compound of the formula: ##STR00078## wherein: is a resin bead; (b) reacting the compound of the formula: ##STR00079## in the presence of trifluoroacetic acid:H.sub.2O:triisopropylsilyl alcohol to provide a compound of the formula: ##STR00080## wherein: W is selected from the group consisting of H.sup.+, Na.sup.+, K.sup.+ or NH.sub.4.sup.+; (c) reacting the compound of the formula: ##STR00081## with sodium hydroxide and a dye compound of the formula: ##STR00082## wherein: X, Y and Z are independently selected from the group consisting of H.sup.+, Na.sup.+, K.sup.+ or NH.sub.4.sup.+; and (d) isolating the compound of the formula: ##STR00083## wherein: W, X, Y and Z are independently selected from the group consisting of H.sup.+, Na.sup.+, K.sup.+ or NH.sub.4.sup.+.