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

HRID 41886

Reaction equation

HRID 41886 reaction equation
[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.C([N:27](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]([NH2:27])=[CH:15][CH:16]=3)=[CH:8][C:6]=2[N:7]=1

Participants

4

Reactant 2

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

Product 1

HCID 866183695-(2-Chloro-4-morpholinothieno[3,2-d]pyrimidin-6-yl)pyridin-2-amine

Reagents, catalysts & solvents 1

HCID 84541-MethylpyrrolidineSolvent

Conditions

Temperature
135 °C

Procedure

A mixture of 2-chloro-6-(6-fluoropyridin-3-yl)-4-morpholinothieno[3,2-d]pyrimidine, 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, which may be Suzuki coupled with a monocyclic heteroaryl, fused bicyclic heterocycle or heteroaryl boronate reagent following General Procedure A.

Workup

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

Sources & evidence

ORD record
ord-c44f186e99ce41fc827f13d753c47952
Source dataset
uspto-grants-2013_09
Patent number
US08536161B2

Linked notes

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