Diisopropylethylamine → 5-(2-Chloro-4-morpholinothieno[3,2-d]pyrimidin-6-yl)pyridin-2-amine

HRID 1910416

Reaktionsgleichung

Reaktionsgleichung von HRID 1910416
[Cl:1][C:2]1[N:3]=[C:4]([N:18]2[CH2:23][CH2:22][O:21][CH2:20][CH2:19]2)[C:5]2[S:10][C:9]([C:11]3[CH:12]=[N:13][C:14](F)=[CH:15][CH:16]=3)=[CH:8][C:6]=2[N:7]=1.[Cl:24][C:25]1[N:26]=[C:27]([N:41]2[CH2:46][CH2:45][O:44][CH2:43][CH2:42]2)[C:28]2[CH:33]=[C:32]([C:34]3[CH:35]=[N:36][C:37](F)=[CH:38][CH:39]=3)[S:31][C:29]=2[N:30]=1.C([N:50](C(C)C)CC)(C)C>CN1CCCC1>[Cl:1][C:2]1[N:3]=[C:4]([N:18]2[CH2:23][CH2:22][O:21][CH2:20][CH2:19]2)[C:5]2[S:10][C:9]([C:11]3[CH:12]=[N:13][C:14]([NH2:26])=[CH:15][CH:16]=3)=[CH:8][C:6]=2[N:7]=1.[Cl:24][C:25]1[N:26]=[C:27]([N:41]2[CH2:46][CH2:45][O:44][CH2:43][CH2:42]2)[C:28]2[CH:33]=[C:32]([C:34]3[CH:35]=[N:36][C:37]([NH2:50])=[CH:38][CH:39]=3)[S:31][C:29]=2[N:30]=1

Komponenten

6

Edukt 3

HCID 81531DiisopropylethylamineHCID 598292882-Chloro-6-(6-fluoropyridin-3-yl)-4-morpholinothieno[3,2-d]pyrimidineHCID 866183712-Chloro-6-(6-fluoropyridin-3-yl)-4-morpholinothieno[2,3-d]pyrimidine

Produkt 2

HCID 866183695-(2-Chloro-4-morpholinothieno[3,2-d]pyrimidin-6-yl)pyridin-2-amineHCID 866183702-Chloro-6-(6-aminopyridin-3-yl)-4-morpholinothieno[2,3-d]pyrimidine

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 84541-MethylpyrrolidineLösungsmittel

Reaktionsbedingungen

Temperatur
135 °C

Versuchsvorschrift

A mixture of 2-chloro-6-(6-fluoropyridin-3-yl)-4-morpholinothieno[3,2-d]pyrimidine or 2-chloro-6-(6-fluoropyridin-3-yl)-4-morpholinothieno[2,3-d]pyrimidine compound, about four equivalents of a primary or secondary amine (R═H, C1-C12 alkyl, C2-C8 alkenyl, C2-C8 alkynyl, C3-C12 carbocyclyl, C2-C20 heterocyclyl, C6-C20 aryl, or C1-C20 heteroaryl), and about two eq. diisopropylethylamine in N-methylpyrrolidine (˜0.1M) is heated to about 130-140° C. in a sealed microwave reactor for 10˜40 min, followed by removal of volatiles under high vacuum. The crude mixture is purified by flash chromatography to give intermediate 2-chloro-6-(6-aminopyridin-3-yl)-4-morpholinothieno[3,2-d]pyrimidine or 2-chloro-6-(6-aminopyridin-3-yl)-4-morpholinothieno[2,3-d]pyrimidine compound, which may be Suzuki coupled with a monocyclic heteroaryl, fused bicyclic heterocycle or heteroaryl boronate reagent following General Procedure A.

Aufarbeitung

  1. customfollowed by removal of volatiles under high vacuum
  2. customThe crude mixture is purified by flash chromatography

Quellen und Nachweise

ORD-Eintrag
ord-9e1023450fd14ced8c76ce06c13c633c
Quelldatensatz
uspto-grants-2013_12
Patentnummer
US08604014B2

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