Iodine → 2-Chloro-6-iodo-7-methyl-4-morpholinothieno[3,2-d]pyrimidine

HRID 41890ノート

反応式

HRID 41890 の反応式
[Cl:1][C:2]1[N:3]=[C:4]([N:12]2[CH2:17][CH2:16][O:15][CH2:14][CH2:13]2)[C:5]2[S:10][CH:9]=[C:8]([CH3:11])[C:6]=2[N:7]=1.ClC1N=C(N2CCOCC2)C2SC=CC=2N=1.C(OC(C1SC=C(C)C=1N)=O)C.[Li]CCCC.[I:51]I>C1COCC1>[Cl:1][C:2]1[N:3]=[C:4]([N:12]2[CH2:13][CH2:14][O:15][CH2:16][CH2:17]2)[C:5]2[S:10][C:9]([I:51])=[C:8]([CH3:11])[C:6]=2[N:7]=1

参加物

7

反応物 5

HCID 807IodineHCID 18434732Ethyl 3-amino-4-methylthiophene-2-carboxylateHCID 202849712-Chloro-4-(morpholin-4-yl)thieno(3,2-d)pyrimidineHCID 598178734-(2-Chloro-7-methylthieno[3,2-d]pyrimidin-4-yl)morpholineHCID 178418339Butyllithium

生成物 1

HCID 595928802-Chloro-6-iodo-7-methyl-4-morpholinothieno[3,2-d]pyrimidine収率 84%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒2 回

反応条件

温度
-40 °C

実験手順

To a solution of 2-chloro-7-methyl-4-morpholinothieno[3,2-d]pyrimidine 39 (3.0 g, 11.1 mmol; prepared according to the procedure for the synthesis of 2-chloro-4-morpholin-4-yl-thieno[3,2-d]pyrimidine but commencing with 3-amino-4-methyl-thiophene-2-carboxylic acid ethyl ester) in THF (60 mL) at −78° C. was added n-BuLi (8.9 mL, 2.5 M in Et2O). The resulting slurry was warmed to −40° C. and stirred 50 min. The reaction mixture was then cooled to −78° C. and a solution of I2 (5.6 g, 22.2 mmol) in THF (30 mL) was added. The solution was warmed to room temperature and stirred 5 h. The reaction was quenched by the addition of water. The organic layer was separated and the aqueous layer was extracted with CH2Cl2. The combined organics were washed with saturated aqueous Na2S2O3, dried over Na2SO4, filtered, and concentrated in vacuo to provide 2-chloro-6-iodo-7-methyl-4-morpholinothieno[3,2-c]pyrimidine 41 (3.8 g, 84% yield).

後処理

  1. customprepared
  2. temperatureThe reaction mixture was then cooled to −78° C.
  3. temperatureThe solution was warmed to room temperature
  4. stirringstirred 5 h
  5. customThe reaction was quenched by the addition of water
  6. customThe organic layer was separated
  7. extractionthe aqueous layer was extracted with CH2Cl2
  8. washThe combined organics were washed with saturated aqueous Na2S2O3
  9. dry with materialdried over Na2SO4
  10. filtrationfiltered
  11. concentrationconcentrated in vacuo

出典と根拠

ORDレコード
ord-6615c6db9821492281ec0b20785c91f1
出典データセット
uspto-grants-2013_09
特許番号
US08536161B2

反応ノート

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