Morpholine → 2-Chloro-4-(morpholin-4-yl)thieno(2,3-d)pyrimidine

HRID 1805783Notes

Reaction equation

HRID 1805783 reaction equation
[NH:1]1[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1.Cl[C:8]1[C:9]2[CH:17]=[CH:16][S:15][C:10]=2[N:11]=[C:12]([Cl:14])[N:13]=1>CO>[Cl:14][C:12]1[N:13]=[C:8]([N:1]2[CH2:6][CH2:5][O:4][CH2:3][CH2:2]2)[C:9]2[CH:17]=[CH:16][S:15][C:10]=2[N:11]=1

Participants

4

Reactant 2

HCID 8083MorpholineHCID 122173242,4-Dichlorothieno[2,3-d]pyrimidine

Product 1

HCID 130381892-Chloro-4-(morpholin-4-yl)thieno(2,3-d)pyrimidine

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

Scheme 6 shows the synthesis of 4-(2-chlorothieno[2,3-d]pyrimidin-4-yl)morpholine 18 starting by cyclization of methyl 2-amino-thiophenecarboxylate 15 (95 g) with chlorosulfonyl isocyanate at low temperature remains (−60° C. to −55° C.) to give thieno[2,3-d]pyrimidine-2,4(1H,3H)-dione 16. Phosphorous oxychloride was added slowly to a cold solution of thieno[2,3-d]pyrimidine-2,4(1H,3H)-dione 16 and N,N-dimethylaniline (0.75 equiv.) in acetonitrile while maintaining the temperature below 25° C. The mixture was then heated to 80-85° C. and stirred for 24 hours to afford dichlorothieno[2,3-d]pyrimidine 17. Morpholine (2.2 equiv.) was added to a solution of 2,4-dichlorothieno[2,3-d]pyrimidine 17 in methanol and stirred at ambient temperature for 1 h to give 18.

Sources & evidence

ORD record
ord-f64dd949bc3e4b958fdefbce859d3a6a
Source dataset
uspto-grants-2013_01
Patent number
US08354528B2

Reaction notes

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