2,6-Dichloro-9-(2,3,5-tri-O-acetyl-beta-D-ribofuranosyl)purine → N-[3-(2-benzothiazolyl)thio-1,1,1-trifluoro-2-propyl]-2-chloroadenosine

HRID 375157Notes

Reaction equation

HRID 375157 reaction equation
Cl.[NH2:2][C@@H:3]([CH2:8][S:9][C:10]1[S:11][C:12]2[CH:18]=[CH:17][CH:16]=[CH:15][C:13]=2[N:14]=1)[C:4]([F:7])([F:6])[F:5].SC1SC2C=CC=CC=2N=1.[C:29]([O:32][C@@H:33]1[C@H:37]([O:38][C:39](=[O:41])[CH3:40])[C@@H:36]([CH2:42][O:43][C:44](=[O:46])[CH3:45])[O:35][C@H:34]1[N:47]1[CH:55]=[N:54][C:53]2[C:48]1=[N:49][C:50]([Cl:57])=[N:51][C:52]=2Cl)(=[O:31])[CH3:30]>N>[C:29]([O:32][C@@H:33]1[C@H:37]([O:38][C:39](=[O:41])[CH3:40])[C@@H:36]([CH2:42][O:43][C:44](=[O:46])[CH3:45])[O:35][C@H:34]1[N:47]1[C:48]2[N:49]=[C:50]([Cl:57])[N:51]=[C:52]([NH:2][CH:3]([CH2:8][S:9][C:10]3[S:11][C:12]4[CH:18]=[CH:17][CH:16]=[CH:15][C:13]=4[N:14]=3)[C:4]([F:7])([F:6])[F:5])[C:53]=2[N:54]=[CH:55]1)(=[O:31])[CH3:30].[S:11]1[C:12]2[CH:18]=[CH:17][CH:16]=[CH:15][C:13]=2[N:14]=[C:10]1[S:9][CH2:8][CH:3]([NH:2][C:52]1[C:53]2[N:54]=[CH:55][N:47]([C:48]=2[N:49]=[C:50]([Cl:57])[N:51]=1)[C@@H:34]1[O:35][C@H:36]([CH2:42][OH:43])[C@@H:37]([OH:38])[C@H:33]1[OH:32])[C:4]([F:7])([F:6])[F:5]

Participants

6

Reactant 3

HCID 102530272,6-Dichloro-9-(2,3,5-tri-O-acetyl-beta-D-ribofuranosyl)purineHCID 228583222-[(R)-2-amino-1,1,1-trifluoro-3-propylthio]benzothiazole hydrochlorideHCID 178418395HCID 178418395, compound

Product 2

HCID 22858284N-[3-(2-benzothiazolyl)thio-1,1,1-trifluoro-2-propyl]-2-chloroadenosineYield 45%HCID 228583082',3',5'-tri-O-acetyl-N-[3-(2-benzothiazolyl)thio-1,1,1-trifluoro-2-propyl]-2-chloroadenosine

Reagents, catalysts & solvents 1

HCID 222AmmoniaSolvent

Procedure

N-[3-(2-Benzothiazolyl)thio-1,1,1-trifluoro-2-propyl]-2-chloroadenosine was prepared according to general method A as described in Example 1 by reacting 2-[(R)-2-amino-1,1,1-trifluoro-3-propylthio]benzothiazole hydrochloride [prepared by a Mitsunobu reaction as described in Example 1 using the above 2-(N-tert-butyloxycarbonyl)amino-1,1,1-trifluoro-3-propanol and 2-mercaptobenzothiazole followed by acidic hydrolysis] (0.13 g, 0.47 mmol) with 9-(2,3,5-tri-O-acetyl-β-D-ribofuranosyl)-2,6-di-chloro-9H-purine (0.21 g, 0.45 mmol). Debenzoylation of the purified 2',3',5'-tri-O-acetyl-N-[3-(2-benzothiazolyl)thio-1,1,1-trifluoro-2-propyl]-2-chloroadenosine in methanolic ammonia (20 ml) (previously saturated at -10° C.) provided the title N-[3-(2-benzothiazolyl)thio-1,1,1-trifluoro-2-propyl]-2-chloroadenosine (0.12 g, 45%) (following column chromatography) [a mixture of (R)- & (S)- diastereoisomers]; 1H NMR (DMSO-d6) δ 3.39-3.49 (1H, m, --CH), 3.58, 3.68 (2H, ABX, H-5'a and H-5'b), 3.98 (1H, q, H-4'), 4.11 -4.18 (2H, m, H-3' and --CH--), 4.47-4.56 (1H, m, H-2'), 5.08 (1H, m, 5'-OH), 5.18-5.28 (1H, m, --CHCH2 --), 5.27, 5.57 (2H, 2d, 2'- and 3'-OH), 5.94 (1H, d, H-1'), 7.08, 7.22, 7.30 (3H, 3 t, Ar-H), 7.71 (1H, d, Ar-H), 8.75 (1H, s, H-8), 8.79 (1H, d, N--H).

Workup

  1. customN-[3-(2-Benzothiazolyl)thio-1,1,1-trifluoro-2-propyl]-2-chloroadenosine was prepared
  2. customprepared by a Mitsunobu reaction

Sources & evidence

ORD record
ord-befda197c4d748cdbadd0d6ea5837ae5
Source dataset
uspto-grants-1996_01
Patent number
US05484774

Reaction notes

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