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

HRID 881224노트

반응식

HRID 881224 반응식
[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

참가 물질

7

반응물 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

생성물 1

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

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매2회

반응 조건

온도
-40 °C

실험 절차

To a solution of 2-chloro-7-methyl-4-morpholinothieno[3,2-d]pyrimidine (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-d]pyrimidine (3.8 g, 84% yield).

후처리

  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

출처 및 근거

ORD 기록
ord-ccab751cd3fc4412bd278edf223889a5
출처 데이터셋
uspto-grants-2015_03
특허 번호
US08993563B2

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