4-Toluenesulfonyl chloride → tert-Butyl 4-(acetylthio)piperidine-1-carboxylate
Reaction equation
C(=[C:4]([OH:22])[C@H]1O[C@@H](N2C3N=CN=C(N)C=3N=C2)[C@H](O)[C@@H]1O)(C)C.C1(C)C(S([C@@]2(N3C4N=CN=C(N)C=4N=C3)O[C@H](C(=C(C)C)O)[C@@H](O)[C@H]2O)(=O)=[O:30])=CC=CC=1.[C:55]1([CH3:65])[CH:60]=CC(S(Cl)(=O)=O)=C[CH:56]=1.[C:66]([O-:69])(=[S:68])[CH3:67].[K+].Br[CH:72]1[CH2:77][CH2:76][NH:75][CH2:74][CH2:73]1.C[O-].[Na+]>CN(C=O)C.N1C=CC=CC=1>[C:55]([O:30][C:4]([N:75]1[CH2:76][CH2:77][CH:72]([S:68][C:66](=[O:69])[CH3:67])[CH2:73][CH2:74]1)=[O:22])([CH3:65])([CH3:60])[CH3:56]Participants
Reactant 6
Product 1
Reagents, catalysts & solvents 2
Procedure
In Scheme 1, above, isopropylideneadenosine 1 is used to synthesize toluenesulfonyl isopropylideneadenosine, 2 (2′,3′-O-isopropylidene-5′-O-toluene-p-sulfonyl adenosine). An anhydrous pyridine solution of commercially available 2′,3′-isopropylideneadenosine 1 is shaken with p-toluenesulfonyl chloride. In a separate reaction, the synthon 4-acetylsulfanyl-piperidine-1-carboxylic acid tert-butyl ester 4 was synthesized using the method of Plettenburg in which potassium thioacetate and 4-bromo-piperidine 3 are heated in DMF. According to modified procedures based on an existing protocol (Isakovic et al., Bioorg. & Med. Chem. Lett. (2009) 19: 2742-2746), synthon 4 is reacted with sodium methoxide to form the thiol, followed by the reaction with 2 to give 4-[6-(6-Amino-purin-9-yl)-2,2-dimethyl-tetrahydro-furo[3,4-d][1,3]dioxol-4-ylmethylsulfanyl]-piperidine-1-carboxylic acid tert-butyl ester 5. Under the TFA/DCM condition, cleavage of the BOC protection group and subsequent reaction of 6 with (2-bromo-ethyl)-carbamic acid tert-butyl ester provides intermediate 7. The deprotection of 7 yields 8, which contains an amino group used to link 8 to the pterin moiety.
Workup
- customIn a separate reaction
Sources & evidence
- ORD record
- ord-cfcdd163f5df44bab87d4a42aeca3d4a
- Source dataset
- uspto-grants-2015_05
- Patent number
- US09029344B2
Reaction notes
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