On November 27, 2014, Armer, Richard; Bingham, Matilda; Morrison, Angus; Carswell, Emma; Elustondo, Fred; Walker, Rolf; Guisot, Nicolas; Lucas, Catherine published a patent.Related Products of 52537-00-5 The title of the patent was Preparation of pyrazolo[3,4-d]pyrimidine derivatives useful as inhibitors of Bruton’s tyrosine kinase. And the patent contained the following:
This invention relates to novel compounds [I; A1-A5 = N or CRa and any two CRa on adjacent A groups form an addnl. (un)substituted nonaromatic carbocyclic or heterocyclic ring; D = (un)substituted C1-6 alkylene optionally containing 1, 2 or 3 N, O, or S atoms; or D = (un)saturated and (un)substituted carbocyclic or heterocyclic moiety optionally substituted with NRb; E = C(:Y)C(R2):C(R4)(R3), SO2 C(R2):C(R4)(R3), cyano, COCH2X, (oxiran-2-yl)(CH2)o, or (oxiran-2-yl)(CH2)oCO; Y = O or NRb; X = Cl, F, Br, or iodo; o = 0-2; Ra = H, halo, C1-6 alkyl, C1-6 haloalkyl, OH, SH, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-8 cycloalkyl, C3-8 cycloalkenyl, NRbRc, cyano, acyl, etc.; Rb, Rc = H, C1-4 alkyl, C1-4 haloalkyl, C1-4 acyl, C3-7 cycloalkyl, or C3-7 halocycloalkyl; R1 = each (un)substituted NH2 or each (un)saturated carbocyclic or heterocyclic moiety; R2, R3, R4 = H, halo , ORb, cyano, -NRbRc, -CH2NRbRc, CO2Rb, C(O)Rbb, C(O)NRbRc, etc.; R5 = H, halo, ORb, C1-6 alkoxy, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-8 cycloalkyl, C3-8 heterocycloalkyl, C3-8 cycloalkenyl, C3-8 heterocycloalkenyl, NRbRc, -CO2Rb, C(O)Rb, or C(O)NRbRc; L1 = a bond, O, or each (un)substituted O(CH2)m, NH, or (CH2)m; m = 1, 2, 3, or 4]. These compounds are Bruton’s tyrosine kinase (BTK) inhibitors and have better activity and better solubility over known compounds, reduced side effects compared to known therapies, convenient pharmacokinetic profile, and a suitable duration of action following dosing. They are useful for treating conditions treatable by the inhibition of Bruton’s tyrosine kinase, for example cancer, lymphoma, leukemia, immunol. diseases, autoimmune diseases, and inflammatory disorders. Thus, Mitsunobu reaction of 3-iodo-1H-pyrazolo[3,4-d]pyrimidin-4-amine with and tert-Bu (3S)-3-hydroxypiperidine-1-carboxylate using Ph3P and DIAD in THF at <5° for 30 min and at room temperature overnight gave tert-Bu 3-(4-amino-3-iodopyrazolo[3,4-d]pyrimidin-1-yl)piperidine-1-carboxylate which underwent Suzuki coupling with 4-[[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]methyl]morpholine in the presence of potassium carbonate and tetrakis(triphenylphosphine)palladium in aqueous dioxane at 100° for 60 min under microwave irradiation to give tert-Bu 3-[(1S)-4-amino-3-[4-(morpholinomethyl)phenyl]pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carboxylate (II; R = tert-butoxycarbonyl). Deprotection of II (R = tert-butoxycarbonyl) with 4 M HCl/dioxane solution for 4 h gave II.HCl (R = H) which underwent acylation with acryloyl chloride in the presence of Et3N at room temperature for 2 h to give II (R = acryloyl). II (R = acryloyl) showed IC50 of 0.1-15 nM against Bruton's tyrosine kinase. The experimental process involved the reaction of 6-Chloro-2,3-dihydro-1H-indole(cas: 52537-00-5).Related Products of 52537-00-5
The Article related to pyrazolopyrimidine preparation inhibitor bruton tyrosine kinase, cancer lymphoma leukemia immunol disease treatment pyrazolopyrimidine preparation, autoimmune disease inflammatory disorder treatment pyrazolopyrimidine preparation and other aspects.Related Products of 52537-00-5
Referemce:
Indole alkaloid derivatives as building blocks of natural products from Bacillus thuringiensis and Bacillus velezensis and their antibacterial and antifungal activity study,
Preparation of Indole Containing Building Blocks for the Regiospecific Construction of Indole Appended Pyrazoles and Pyrroles