Phosphorus oxychloride → 4-Chloro-7-methoxy-2-[4-(propan-2-yl)-1,3-thiazol-2-yl]quinoline

Participants

Reaction Conditions

Reaction Steps

Step G) A suspension of 1.3 g (4.3 mmol) of 2-(4-Isopropylthiazol-2-yl)-7-methoxyquinolin-4-ol, product of step F, in 60 mL of POCl3 was heated to reflux for 2 h. The solvent was removed in vacuo, the residue diluted with ice cold water and the mixture adjusted to pH 9 while cooling to 0° C. This aqueous solution was extracted several times with EtOAc. The combined EtOAc extracts were washed once with brine, pH 4 buffer, dried (MgSO4), and concentrated to afford 0.89 g (64%) of 4-Chloro-2-(4-isopropylthiazol-2-yl)-7-methoxyquinoline as a yellow solid: 1H NMR (500 MHz, CDCl3) δ 1.38 (d, J=7 Hz, 6H), 3.19 (m, 1H), 3.98 (s, 3H), 7.06 (s, 1H), 7.26 (m, 1H), 7.47 (d, J=2 Hz, 1H), 8.10 (d, J=9 Hz, 1H), 8.31 (s, 1H). LC-MS m/e 319 (retention time: 2.20, method D). Preparation of Example 26, (1S,4R,6S,14S,18R)-7-cis-14-tert-butoxycarbonylamino-18-hydroxy-2,15-dioxo-3,16-diazatricyclo[14.3.0.04,6]nonadec-7-ene-4-carboxylic acid using Steps 26i-26iv. Step 26i: Preparation of 1-(2(S)-tert-Butoxycarbonylamino-non-8-enoyl)-4(R)-hydroxy-pyrrolidine-2(S)-carboxylic acid methyl ester

Provenance & Evidence