Capimorelin, Capromorelin, CP-424391-18(tartrate), CP-424391

卡普瑞林 酒石酸卡莫瑞林 Chemical Name: 2-Amino-N-[2-[3a(R)-benzyl-2-methyl-3-oxo-3,3a,4,5,6,7-hexahydro-2H-pyrazolo[4,3-c]pyridin-5-yl]-1(R)-(benzyloxymethyl)-2-oxoethyl]isobutyramide
CAS No. 193273-66-4, 193273-69-7 (L-tartrate(1:1)), 193270-49-4 (monoHCl), 193273-67-5 (monomesylate)
项目整合开发状态: Phase II
项目研究机构: Pfizer (Originator)
合成路线:The intermediate dipeptide (VI) was prepared by two similar ways.Treatment of N-Boc-O-benzyl-D-serine (I) with MeI and K2CO3 produced the methyl ester (II).Subsequent deprotection of the Boc group of (II) with trifluoroacetic acid gave aminoester (III),which was coupled with N-Boc-alpha-methylalanine (IV) using EDC and HOBt yielding (V).Hydrolysis of the resulting dipeptide ester (V) then provided intermediate (VI).In an alternative procedure,N-Boc-alpha-methyl alanine (IV) was activated as the N-hydroxysuccinimidyl ester (VII),which was condensed with O-benzyl-D-serine (VIII) to produce dipeptide (VI).

合成路线:Methyl 4-oxopiperidine-3-carboxylate (IX) was protected as the tert-butyl carbamate (X) with Boc2O.This was alkylated with benzyl bromide in the presence of NaH to provide the racemic benzyl derivative (XI).Subsequent cyclization of (XI) with methylhydrazine produced the pyrazolopyridine (XII),which was deprotected with trifluoroacetic acid.The resulting amine (XIII) was then coupled with dipeptide (VI) using EDC and HOBt to afford the diastereomeric amides (XIV).After chromatographic isolation of the (R,R)-diastereoisomer,acid deprotection of the Boc group furnished the title compound.