Reaktion #1592066

Reaktionsgleichung

6-{[5-({(1R,2S)-2-[(tert-butoxycarbonyl)amino]cyclohexyl}amino)-2-carbamoylpyridin-3-yl]amino}-2-methylpyridine-3-carboxylic acid

6-[(5-{[(1R,2S)-2-aminocyclohexyl]amino}-2-carbamoylpyridin-3-yl)amino]-2-methylpyridine-3-carboxylic acid TFA salt

dimethylamine

N,N′-diisopropylethylamine

1-propanephosphonic acid cyclic anhydride

→

tert-butyl {(1S,2R)-2-[(6-carbamoyl-5-{[5-(dimethylcarbamoyl)-6-methylpyridin-2-yl]amino}pyridin-3-yl)amino]cyclohexyl}carbamate

Lösungsmittel

DMF

Reaktionsbedingungen

Aufarbeitung

1. 1
   EinengenThe reaction mixture was concentrated under reduced pressure
2. 2
   SonstigeThe residue was purified by reverse phase HPLC (0-100% acetonitrile/water with 0.1% TFA, linear gradient)

Vorschrift

To a solution of 6-{[5-({(1R,2S)-2-[(tert-butoxycarbonyl)amino]cyclohexyl}amino)-2-carbamoylpyridin-3-yl]amino}-2-methylpyridine-3-carboxylic acid (from Step 4 of Example 16) (45 mg, 0.093 mmol), dimethylamine (2.0 M in methanol, 0.093 mL, 0.19 mmol) and N,N′-diisopropylethylamine (0.032 mL, 0.19 mmol) in DMF (1 mL) was added dropwise 1-propanephosphonic acid cyclic anhydride (50% in ethyl acetate, 0.065 mL, 0.11 mmol) at 0° C. The reaction mixture was stirred for 2 hours while warming to room temperature. The reaction mixture was concentrated under reduced pressure. The residue was purified by reverse phase HPLC (0-100% acetonitrile/water with 0.1% TFA, linear gradient) to afford tert-butyl {(1S,2R)-2-[(6-carbamoyl-5-{[5-(dimethylcarbamoyl)-6-methylpyridin-2-yl]amino}pyridin-3-yl)amino]cyclohexyl}carbamate. MS ESI calc'd. for C26H38N7O4 [M+H]+ 512. found 512. 1H NMR (500 MHz, DMSO-d6) δ 11.95 (s, 1H), 8.51 (s, 1H), 7.88 (s, 1H), 7.62 (s, 1H), 7.42 (d, J=8.1 Hz, 1H), 7.29 (s, 1H), 6.65 (d, J=8.2 Hz, 1H), 6.61-6.51 (m, 1H), 6.21-6.03 (m, 1H), 3.87-3.74 (m, 1H), 3.69-3.56 (m, 1H), 2.97 (s, 3H), 2.81 (s, 3H), 2.33 (s, 3H), 1.87-1.74 (m, 1H), 1.74-1.63 (m, 1H), 1.64-1.42 (m, 4H), 1.33 (s, 2H), 1.27 (s, 9H).

Quelle