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

HRID 2098587

Reaction equation

HRID 2098587 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.[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

Participants

6

Reactant 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

Product 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

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 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 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-a843738cb3104daa97e1783e54c1124b
Source dataset
uspto-grants-2013_05
Patent number
US08450315B2

Linked notes

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