ASP ?
(2R)-2-(4-cyclopropanesulfonyl-3-cyclopropylphenyl)-N-[5-(hydroxymethyl)pyrazin-2-yl]-3-[(R)-3-oxocyclopentyl]propanamide
- Molecular Weight, 483.58
- [α]D20 −128.7 (c 1.00, MeOH);
- 1H NMR (DMSO-d6, 400 MHz) δ 11.07 (s, 1H), 9.20 (d, J = 1.4 Hz, 1H), 8.41 (d, J = 1.4 Hz, 1H), 7.79 (d, J = 8.2 Hz, 1H), 7.41 (dd, J = 8.2, 1.8 Hz, 1H), 7.15 (d, J = 1.8 Hz, 1H), 5.52 (t, J = 5.7 Hz, 1H), 4.56 (d, J = 6.0 Hz, 2H), 4.04 (t, J = 7.6 Hz, 1H), 3.03–2.97 (m, 1H), 2.79 (tt, J = 8.4, 5.1 Hz, 1H), 2.25–1.81 (m, 8H), 1.53–1.47 (m, 1H), 1.17–1.12 (m, 2H), 1.08–1.02 (m, 4H), 0.89–0.84 (m, 2H);
- 13C NMR (DMSO-d6, 101 MHz) δ 218.5, 171.8, 152.1, 147.3, 145.7, 143.2, 140.3, 138.2, 134.8, 129.0, 125.3, 125.1, 62.5, 49.9, 44.4, 38.4, 38.2, 34.8, 32.1, 29.1, 12.4, 10.8, 10.7, 5.8;
- FTIR (ATR, cm–1) 3544, 3257, 1727, 1692, 1546, 1507, 1363, 1285, 1149, 719;
- HRMS (ESI) m/z [M + Na]+ calcd for C25H29N3O5S 506.1726, found 506.1747.
- Anal. Calcd for C25H29N3O5S: C, 62.09; H, 6.04; N, 8.69. Found: C, 61.79; H, 6.19; N, 8.62.
| Inventors | Masahiko Hayakawa, Yoshiyuki Kido, Takahiro Nigawara, Mitsuaki Okumura, Akira Kanai, Keisuke Maki, Nobuaki Amino |
| Applicant | Astellas Pharma Inc. |
Synthesis
contd…………………………..
PATENT
- PAPER
A Practical and Scalable Synthesis of a Glucokinase Activator via Diastereomeric Resolution and Palladium-Catalyzed C–N Coupling Reaction
, Yasuhiro Morinaga†, Makoto Kasai†, Takao Hashimoto†, Yuji Takahama†, Atsushi Ohigashi†, Satoshi Yonishi‡, and Motohiro Akazome§
Here we describe the research and development of a process for the practical synthesis of glucokinase activator (R)-1 as a potential drug for treating type-2 diabetes. The key intermediate, chiral α-arylpropionic acid (R)-2, was synthesized in high diastereomeric excess through the diasteromeric resolution of 7 without the need for a chiral resolving agent. The counterpart 2-aminopyrazine derivative 3 was synthesized using a palladium-catalyzed C–N coupling reaction. This efficient process was demonstrated at the pilot scale and yielded 19.0 kg of (R)-1. Moreover, an epimerization process to obtain (R)-7 from the undesired (S)-7 was developed.
Hayakawa, M.; Kido, Y.; Nigawara, T.; Okumura, M.; Kanai, A.; Maki, K.; Amino, N. PCT Int. Appl. WO/2009/091014 A1 20090723,2009.
https://www.astellas.com/en/ir/library/pdf/3q2017_rd_en.pdf
///////////1174229-89-0, ASTELLAS, Glucokinase Activator, TYPE 2 DIABETES, PRECLINICAL, ASP ?, WO 2009091014, Masahiko Hayakawa, Yoshiyuki Kido, Takahiro Nigawara, Mitsuaki Okumura, Akira Kanai, Keisuke Maki, Nobuaki Amino, WO2009091014,
O=C(Nc1cnc(cn1)CO)[C@H](C[C@@H]2CC(=O)CC2)c3ccc(c(c3)C4CC4)S(=O)(=O)C5CC5
Filed under: DIABETES, Preclinical drugs Tagged: 1174229-89-0, Akira Kanai, ASP ?, astellas, Glucokinase Activator, Keisuke Maki, Masahiko Hayakawa, Mitsuaki Okumura, Nobuaki Amino, preclinical, Takahiro Nigawara, TYPE 2 DIABETES, WO 2009091014, WO2009091014, Yoshiyuki Kido
