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

HRID 41890Notes

Reaction equation

HRID 41890 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

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).

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-6615c6db9821492281ec0b20785c91f1
Source dataset
uspto-grants-2013_09
Patent number
US08536161B2

Reaction notes

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