CH4630808
syn https://newdrugapprovals.org/2018/07/02/ch4630808/
Paper
Development of a Kilogram-Scale Synthesis of a Novel Anti-HCV Agent, CH4930808
CH4630808 corrected
Tsuyoshi Haneishi*† 
, Yoshiaki Kato‡, Hiroshi Fukuda†, Tomoyuki Shimamura‡, Takemi Tanokura‡, Akira Hiraide‡, Kaichiro Koyama‡, Masato Fudesaka‡, Kenji Maeda‡, Nobuyuki Nakata‡, Masahiro Nagase‡, Takahiko Yabuzaki‡, Hiroaki Takao‡, Masaharu Kigawa‡, Hitoshi Shimizu‡, and Makoto Shimizu§
, Yoshiaki Kato‡, Hiroshi Fukuda†, Tomoyuki Shimamura‡, Takemi Tanokura‡, Akira Hiraide‡, Kaichiro Koyama‡, Masato Fudesaka‡, Kenji Maeda‡, Nobuyuki Nakata‡, Masahiro Nagase‡, Takahiko Yabuzaki‡, Hiroaki Takao‡, Masaharu Kigawa‡, Hitoshi Shimizu‡, and Makoto Shimizu§
† Research Division, Chugai Pharmaceutical Co., Ltd., 1-135 Komakado, Gotemba, Shizuoka 412-8513, Japan
‡ Pharmaceutical Technology Division, Chugai Pharmaceutical Co., Ltd., 5-5-1 Ukima, Kita-ku, Tokyo 115-8543, Japan
§ Department of Chemistry for Materials, Graduate School of Engineering, Mie University, Tsu, Mie 514-8507, Japan
Org. Process Res. Dev., 2018, 22 (2), pp 236–240
DOI: 10.1021/acs.oprd.7b00383
Abstract
Herein, we report the kilogram-scale synthesis of CH4930808 (1) CH 4630808 CORRECTED, a novel anti-hepatitis C virus agent. While pursuing improved productivity using many through-process strategies, we conducted scrupulous impurity control. Finally, we successfully developed a practical and scalable process for the synthesis of (1·1.5Na·2.5H2O), by which we prepared 3.28 kg of the active pharmaceutical ingredient for clinical studies
1H-NMR and 13C-NMR spectra of compound 5·HCl S 3– S 4
1H-NMR spectra of compound 1·1.5 Na·2.5 H2O S 5
13C-NMR spectra compound 1·1.5 Na·2.5 H2O S 6
1H-COSY spectra of compound 1·1.5 Na·2.5 H2O S 7 – S 8
DEPT spectra of compound 1·1.5 Na·2.5 H2O S 9 – S 10
HMBC spectra of compound 1·1.5 Na·2.5 H2O S 11 – S 17
MASS
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