Chlorosulfonyl isocyanate → thieno[2,3-d]pyrimidine-2,4-diol
Reaction equation
ClC1N=C(N2CC[O:14][CH2:13]C2)C2C=CSC=2N=1.[NH2:17][C:18]1(C(OC)=O)[CH2:22][CH:21]=[CH:20][S:19]1.ClS([N:31]=[C:32]=[O:33])(=O)=O>>[NH:17]1[C:18]2[S:19][CH:20]=[CH:21][C:22]=2[C:13](=[O:14])[NH:31][C:32]1=[O:33]Participants
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.
Workup
- custom(−60° C. to −55° C.)
Sources & evidence
- ORD record
- ord-804a309686c74ea2a038ee36b8fb0519
- Source dataset
- uspto-grants-2013_04
- Patent number
- US08431694B1
Reaction notes
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