Methanol → HCID 178518646, compound

HRID 600455Notes

Reaction equation

HRID 600455 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([F:8])=[CH:4][C:3]=1[NH:9][C:10]1[N:18]=[C:17]2[C:13]([NH:14][C:15](=[O:26])[N:16]2[C@H:19]2[CH2:24][CH2:23][C@H:22]([OH:25])[CH2:21][CH2:20]2)=[C:12]([Cl:27])[N:11]=1.CO.[CH3:30]OC(OC)OC.C1(C)C=CC(S(O)(=O)=O)=CC=1>O.C(#N)C>[Cl:27][C:12]1[N:11]=[C:10]([N:9]2[C:3]3[CH:4]=[C:5]([F:8])[CH:6]=[CH:7][C:2]=3[N:1]=[CH:30]2)[N:18]=[C:17]2[C:13]=1[NH:14][C:15](=[O:26])[N:16]2[C@H:19]1[CH2:20][CH2:21][C@H:22]([OH:25])[CH2:23][CH2:24]1

Participants

7

Reactant 4

HCID 887MethanolHCID 6101p-Toluenesulfonic acidHCID 9005Trimethyl orthoformateHCID 178507655HCID 178507655, compound

Product 1

HCID 178518646HCID 178518646, compoundYield 88%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6342AcetonitrileSolvent

Procedure

To a flask containing crude 2-(2-amino-5-fluorophenylamino)-6-chloro-9-(trans-4-hydroxycyclohexyl)-7H-purin-8(9H)-one (12 mg, 0.03 mmol) was added anhydrous methanol (3 mL), followed by anhydrous trimethylorthoformate (0.5 mL) and p-toluenesulfonic acid (catalytic) and the reaction mixture was stirred under Ar at room temperature for 18 h (HPLC monitoring). A solution 10% acetonitrile in water (total volume 10 mL) was added and a pale yellow solid precipitated. Filtration under vacuum provided the desired product as a pale yellow solid (10.6 mg, 88% yield). 1H NMR (300 MHz, CDCl3+CD3OD) δ, ppm: 9.07 (br s, 1H), 8.30 (br d, 1H), 7.82-7.70 (m, 1H), 7.27-7.15 (m, 1H), 4.48-4.42 (m, 1H), 3.88-3.80 (m, 1H), 2.67-2.50 (m, 2H), 2.33-2.18 (m, 2H), 2.10-1.95 (m, 2H), 1.70-1.56 (m, 2H); MS (EI) m/z 403.1 (MH)+.

Workup

  1. customa pale yellow solid precipitated
  2. filtrationFiltration under vacuum

Sources & evidence

ORD record
ord-efac5eacea304684b55f103ac722a2c7
Source dataset
uspto-grants-2011_03
Patent number
US07902187B2

Reaction notes

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