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

HRID 2098604Notes

Reaction equation

HRID 2098604 reaction equation
[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

Participants

7

Reactant 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

Product 1

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

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-40 °C

Procedure

Also, 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).

Workup

  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

Sources & evidence

ORD record
ord-a96a53b14bda4db2b4ed3f49fbbf042b
Source dataset
uspto-grants-2013_05
Patent number
US08450315B2

Reaction notes

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