Triethylamine → 5-Amino-7-chloro-3-(2,3,5'-tri-O-acetyl-beta-D-ribofuranosyl)-thiazolo[4,5-d]pyrimidin-2-one

HRID 549795Notes

Reaction equation

HRID 549795 reaction equation
[NH2:1][C:2]1[NH:3][C:4](=O)[C:5]2[S:10][C:9](=[O:11])[N:8]([C@@H:12]3[O:24][C@H:23]([CH2:25][O:26][C:27](=[O:29])[CH3:28])[C@@H:18]([O:19][C:20](=[O:22])[CH3:21])[C@H:13]3[O:14][C:15](=[O:17])[CH3:16])[C:6]=2[N:7]=1.C(N(CC)CC)C.O=P(Cl)(Cl)[Cl:40].C([O-])(O)=O.[Na+]>C(Cl)(Cl)Cl>[NH2:1][C:2]1[N:3]=[C:4]([Cl:40])[C:5]2[S:10][C:9](=[O:11])[N:8]([C@@H:12]3[O:24][C@H:23]([CH2:25][O:26][C:27](=[O:29])[CH3:28])[C@@H:18]([O:19][C:20](=[O:22])[CH3:21])[C@H:13]3[O:14][C:15](=[O:17])[CH3:16])[C:6]=2[N:7]=1

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 24813Phosphorus oxychlorideHCID 516892Sodium BicarbonateHCID 1354347855-amino-3-(2,3,5-tri-O-acetyl-beta-ribofuranosyl)thiazolo(4,5-d)pyrimidine-2,7-dione

Product 1

HCID 595339205-Amino-7-chloro-3-(2,3,5'-tri-O-acetyl-beta-D-ribofuranosyl)-thiazolo[4,5-d]pyrimidin-2-oneYield 87%

Reagents, catalysts & solvents 1

HCID 6212ChloroformSolvent

Procedure

To a solution of 25 (0.84 g, 1.90 mmol) in CHCl3 (9 mL) was added triethylamine (0.50 mL, 3.59 mmol) and POCl3 (1.60 mL, 17.1 mmol). After heating at reflux for 16 h, the reaction mixture was cooled to room temperature and poured onto ice and sat. aq. NaHCO3 (150 mL). The resulting mixture was extracted with CH2Cl2 (3×75 mL) and the combined organic layers dried (MgSO4). Concentration followed by flash chromatography (9:1/CH2Cl2:EtOAc) afforded 708 mg (87%) of product as a white solid, m.p. 101-103° C. 1H NMR (400 MHz, CDCl3) δ 6.10 (d, J=2.8 Hz, 1H), 6.01 (dd, J=5.6, 3.2 Hz, 1H), 5.92 (t, J=6.0 Hz, 1H), 5.42 (s, 2), 4.97 (dd, J=11.6, 3.6 Hz, 1H), 4.32 (m, 1), 4.21 (dd, J=12.0, 5.2 Hz, 1H), 2.12 (s, 6H), 2.06 (s, 3H).

Workup

  1. temperatureAfter heating
  2. temperatureat reflux for 16 h
  3. extractionThe resulting mixture was extracted with CH2Cl2 (3×75 mL)
  4. dry with materialthe combined organic layers dried (MgSO4)
  5. concentrationConcentration

Sources & evidence

ORD record
ord-149debdc84b44c229ecffaa1ed0e31a1
Source dataset
uspto-grants-2011_05
Patent number
US07943759B2

Reaction notes

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