Hydrochloric Acid → HCID 86705753, compound

A cooled (ice bath) solution of trifluoroacetic acid (2.9 mL, 38 mmol) in water (0.34 mL, 19 mmol) was added to a flask of 1-(3-((((3aR,4S,6R,6aS)-6-(6-amino-9H-purin-9-yl)-2,2-dimethyltetrahydro-3aH-cyclopenta[d][1,3]dioxol-4-yl)methyl)(methyl)amino)prop yl)-3-(4-(tert-butyl)phenyl)urea (0.056 g, 0.10 mmol). The reaction mixture was stirred for 5 min and the reaction mixture was then stirred at room temperature for 1.5 hours. The reaction mixture was concentrated in vacuo and taken up in CH2Cl2 (60 mL) and washed with 10% aqueous NH4OH (1×18 mL). The separated aqueous layer was extracted with 10% MeOH/CH2Cl2 (3×18 mL) and the cloudy combined organics (pH>7) were diluted with MeOH (5 mL) to afford a clear solution, which was dried with MgSO4 and concentrated to afford a light tan semi-solid residue. This residue was taken up in 1 ml MeOH and 1N HCl (aq) added (0.1 ml, 0.1 mmol). All volatiles removed in vacuo to yield a tan resin. All efforts to form a solid via lyophilization were unsuccessful so the residue was taken up in 3 mls H2O and 20 mls MeCN added. The resulting cloudy suspension was concentrated to a tan solid which was taken up in MeOH (0.5 ml) and transferred to a vial. N2 passed over the methanolic solution until dryness. The resulting solid was further placed on the lyophilizer at room temperature overnight to obtain 1-(3-((((1S,2R,3S,4R)-4-(6-amino-9H-purin-9-yl)-2,3-dihydroxycyclopentyl)methyl)(methyl)amino)propyl)-3-(4-(tert-butyl)phenyl)urea hydrochloride (0.024 g; Yield=43%). MS (ESI+) for C26H38N8O3 m/z 511.5 [M+H]+; MS (ESI−) for C26H38N8O3 m/z 509.6 [M−H]−; HPLC purity>97% (ret. time, 2.936 min). 1H NMR (400 MHz, d4-MeOH) δ 8.44-8.39 (m, 2H), 7.29-7.26 (m, 4H), 5.06-4.99 (m, 1H), 4.64-4.58 (m, 1H), 4.31-4.26 (m, 1H), 3.70-3.63 (m, 1H), 3.53-3.47 (m, 1H), 3.28-3.22 (m, 1H), 3.15-3.10 (m, 2H), 2.99-2.98 (m, 3H), 2.51-2.26 (m, 2H), 2.11-1.99 (m, 2H), 1.30-1.27 (m, 11H).

1. stirringthe reaction mixture was then stirred at room temperature for 1.5 hours
2. concentrationThe reaction mixture was concentrated in vacuo
3. washwashed with 10% aqueous NH4OH (1×18 mL)
4. extractionThe separated aqueous layer was extracted with 10% MeOH/CH2Cl2 (3×18 mL)
5. additionwere diluted with MeOH (5 mL)
6. customto afford a clear solution, which
7. dry with materialwas dried with MgSO4
8. concentrationconcentrated
9. customto afford a light tan semi-solid residue
10. customAll volatiles removed in vacuo
11. customto yield a tan resin
12. customAll efforts to form a solid via lyophilization
13. concentrationThe resulting cloudy suspension was concentrated to a tan solid which
14. waitThe resulting solid was further placed on the lyophilizer at room temperature overnight

ORD record

ord-9730002aa3dc482ab34e796bf78d604b

Source dataset

uspto-grants-2016_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09394310B2