Ammonia → 2-chloro-N{(R)-1-[5-methyl(1,3,4-thiadiazol-2-yl)]thio-2-propyl}adenosine

HRID 375147Notes

Reaction equation

HRID 375147 reaction equation
Cl.[NH2:2][C@H:3]([CH3:12])[CH2:4][S:5][C:6]1[S:7][C:8]([CH3:11])=[N:9][N:10]=1.C([O:21][C@@H:22]1[C@H:26]([O:27]C(=O)C2C=CC=CC=2)[C@@H:25]([CH2:36][O:37]C(=O)C2C=CC=CC=2)[O:24][C@H:23]1[N:46]1[CH:54]=[N:53][C:52]2[C:47]1=[N:48][C:49]([Cl:56])=[N:50][C:51]=2Cl)(=O)C1C=CC=CC=1.N>>[Cl:56][C:49]1[N:50]=[C:51]([NH:2][C@H:3]([CH3:12])[CH2:4][S:5][C:6]2[S:7][C:8]([CH3:11])=[N:9][N:10]=2)[C:52]2[N:53]=[CH:54][N:46]([C:47]=2[N:48]=1)[C@@H:23]1[O:24][C@H:25]([CH2:36][OH:37])[C@@H:26]([OH:27])[C@H:22]1[OH:21]

Participants

4

Reactant 3

HCID 222AmmoniaHCID 116930649-(2,3,5-tri-O-benzoyl-beta-D-ribofuranosyl)-2,6-dichloro-9H-purineHCID 228583242-[(R)-2-amino-1-propylthio]-5-methyl-[1,3,4]-thiadiazole hydrochloride

Product 1

HCID 228582812-chloro-N{(R)-1-[5-methyl(1,3,4-thiadiazol-2-yl)]thio-2-propyl}adenosineYield 53.2%

Procedure

The title compound was prepared according to method A as described above in Example 1 by reacting 2-[(R)-2-amino-1-propylthio]-5-methyl-[ 1,3,4]-thiadiazole hydrochloride [prepared by alkylation of 2-mercapto-5-methyl-(1,3,4)-thiadiazole (1.32 g, 10 mmol) using methanesulphonic acid, 2-[(R)-N-tert-butyloxycarbonylamino]-1-propyl ester (3.04 g, 12 mmol) followed by acidic hydrolysis] (1.01 g, 4.47 mmol) with 9-(2,3,5-tri-O-benzoyl-β-D-ribofuranosyl)-2,6-dichloro-9H-purine (2.36 g, 3.73 mmol), followed by debenzoylation of the purified product using methanolic ammonia. This provided the title 2-chloro-N{(R)-1-[5-methyl(1,3,4-thiadiazol-2-yl)]thio-2-propyl}adenosine (0.94 g, 53%) as a foam after column chromatography. 1H NMR (DMSO-d6) δ 1.35 (3H, d, --CHCH3), 2.67 (3H, s, --CH3), 3.53-3.61 (2H, m, H-5'a and H-5'b), 3.96 (1H, q, H-4), 4.14 (1H, q, H-3'), 4.52 (1H, q, H- 2'), 5.07 (1H, t, 5'-OH), 5.22, 5.50 (2H, 2d, 2'- and 3'-OH), 5.83 (1H, d, H-1'), 8.33-8.46 (2H, m, H-8 and --NH). HPLC retention time 9.9 min [gradient elution, 20-80% acetonitrile/water (containing 0.1% TFA)].

Workup

  1. customThe title compound was prepared

Sources & evidence

ORD record
ord-5364e9d6158f4842bbefe7b6e6542ea1
Source dataset
uspto-grants-1996_01
Patent number
US05484774

Reaction notes

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