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2,4,6-Tris(1-methylethyl)benzenesulfonyl chloride → 5-Acetylamino-7-(2,4,6-triisopropyl-benzenesulfonyloxy)-3-(2,3,5-tri-o-acetyl-beta-d-ribofuranosyl)thiazolo[4,5-d]pyrimidin-2-one

HRID 19474
Notes
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Reaction equation

HRID 19474 reaction equation
[C:1]([NH:4][C:5]1[NH:6][C:7](=[O:33])[C:8]2[S:13][C:12](=[O:14])[N:11]([C@@H:15]3[O:27][C@H:26]([CH2:28][O:29][C:30](=[O:32])[CH3:31])[C@@H:21]([O:22][C:23](=[O:25])[CH3:24])[C@H:16]3[O:17][C:18](=[O:20])[CH3:19])[C:9]=2[N:10]=1)(=[O:3])[CH3:2].[CH:34]([C:37]1[CH:42]=[C:41]([CH:43]([CH3:45])[CH3:44])[CH:40]=[C:39]([CH:46]([CH3:48])[CH3:47])[C:38]=1[S:49](Cl)(=[O:51])=[O:50])([CH3:36])[CH3:35]>C(Cl)Cl.CN(C1C=CN=CC=1)C>[C:1]([NH:4][C:5]1[N:6]=[C:7]([O:33][S:49]([C:38]2[C:39]([CH:46]([CH3:47])[CH3:48])=[CH:40][C:41]([CH:43]([CH3:45])[CH3:44])=[CH:42][C:37]=2[CH:34]([CH3:36])[CH3:35])(=[O:51])=[O:50])[C:8]2[S:13][C:12](=[O:14])[N:11]([C@@H:15]3[O:27][C@H:26]([CH2:28][O:29][C:30](=[O:32])[CH3:31])[C@@H:21]([O:22][C:23](=[O:25])[CH3:24])[C@H:16]3[O:17][C:18](=[O:20])[CH3:19])[C:9]=2[N:10]=1)(=[O:3])[CH3:2]
ParticipantsProcedureWorkupSources & evidenceReaction notes

Participants

5

Reactant 2

HCID 810422,4,6-Tris(1-methylethyl)benzenesulfonyl chlorideHCID 1355085035-Acetylamino-3-(2,3,5'-tri-O-acetyl-beta-D-ribofuranosyl)-thiazolo[4,5-d]pyrimidine-2,7-dione

Product 1

HCID 208186525-Acetylamino-7-(2,4,6-triisopropyl-benzenesulfonyloxy)-3-(2,3,5-tri-o-acetyl-beta-d-ribofuranosyl)thiazolo[4,5-d]pyrimidin-2-oneYield 92%

Reagents, catalysts & solvents 2

HCID 14284
4-(Dimethylamino)pyridine
Catalyst
HCID 6344DichloromethaneSolvent

Procedure

The intermediate from Step 1 above (500 mg, 0.98 mmol) was dissolved in DCM (15 mL) at ambient temperature. DMAP (7.3 mg, 0.06 mmol), and TEA (16 ml, 11 mmol) were added to the solution, followed by 2,4,6-triisopropylbenzenesulfonyl chloride (454 mg, 1.5 mmol). After 1 h the reaction had gone to completion, the crude mixture was concentrated, and then purified by flash chromatography (SiO2, 10% EtOAc—CHCl3), affording 690 mg (92%) of 5-acetylamino-7-(2,4,6-triisopropyl-benzenesulfonyloxy)-3-(2′,3′,5′-tri-O-acetyl-β-D-ribofuranosyl)thiazolo[4,5-d]pyrimidin-2-one as a foaming white solid 17: 74.5-76.3° C.; Rf=0.7 (SiO2, 20% EtOAc—CHCl3); 1H (400 MHz, d6-DMSO) δ 10.83 (s, 1H), 7.39 (s, 2H), 6.03 (d, J=4.0, 1H), 5.91-5.96 (m, 1H), 5.69 (t, J=6.4, 1H), 4.30-4.70 (m, 1H), 4.22-4.26 (m, 1H), 4.16-4.20 (m, 1H), 3.90-4.00 (m, 2H), 2.97-3.01 (m, 1H), 2.07 (s, 3H), 2.06 (s, 3H), 2.04 (s, 3H), 1.88 (s, 3H), 1.17-1.25 (m, 18H).

Workup

  1. concentrationthe crude mixture was concentrated
  2. custompurified by flash chromatography (SiO2, 10% EtOAc—CHCl3)

Sources & evidence

ORD record
ord-a755111df7a4480a98456d1fe004ccc7
Source dataset
uspto-grants-2010_06
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US07745415B2

Reaction notes

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On this pageParticipantsProcedureWorkupSources & evidenceReaction notes