Acetyl chloride → 2-chloro-7H-purine

HRID 1259266Notes

Reaction equation

HRID 1259266 reaction equation
C1[C@H]([N:6]2[C:10]3[N:11]=[C:12]([Cl:16])[N:13]=[C:14](N)[C:9]=3[N:8]=[CH:7]2)O[C@H](CO)[C@H]1O.C(Cl)(=O)C.N([O-])=O.C([N+](CC)(CC)CC)C1C=CC=CC=1>>[Cl:16][C:12]1[N:11]=[C:10]2[C:9]([NH:8][CH:7]=[N:6]2)=[CH:14][N:13]=1

Participants

4

Reactant 3

HCID 6367Acetyl chlorideHCID 20279CladribineHCID 11149117Benzyltriethylammonium nitrite

Product 1

HCID 5193142-chloro-7H-purine

Procedure

In preferred embodiments of the present invention, CldAdo is synthesized by employing acetyl chloride and benzyltriethylammonium nitrite (BTEA-NO2)-mediated diazotization/chloro-dediazoniation of 6-O-(2,4,6-triisopropylbenzenesulfonyl) (TiPBS) or 6-chloro derivatives that are readily obtained from dGuo. Non-aqueous diazotization/chloro-dediazoniation (acetyl chloride/benzyltriethylammonium nitrite) of 2, 2′b, or 5 gave the 2-chloropurine derivatives 3, 3′b, or 6, respectively. This new procedure for non-aqueous diazotization/chloro-dediazoniation27 (AcCl/BTEA-NO2/CH2Cl2/−5 to 0° C.) worked well for replacement of the 2-amino group of 2, 2′b, and 5 with chlorine to give 3a (89%), 3b (90%), 3′b (87%), 6a (95%), and 6b (91%).

Workup

  1. customare readily obtained from dGuo

Sources & evidence

ORD record
ord-fa74c7d5d15141d4837358028153933c
Source dataset
uspto-grants-2013_06
Patent number
US08466275B2

Reaction notes

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