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

HRID 523359Notes

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

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

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

Sources & evidence

ORD record: ord-738fa13fd63b492c87d7172e85e6d231
Source dataset: uspto-grants-2016_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09335320B2

Reaction notes

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