Trimethyl orthoformate → HCID 59799574, compound

HRID 2074155Notes

Reaction equation

HRID 2074155 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:25])[N:16]2[CH:19]2[CH2:24][CH2:23][O:22][CH2:21][CH2:20]2)=[C:12]([Cl:26])[N:11]=1.[CH3:27]OC(OC)OC>CO.CS(O)(=O)=O>[Cl:26][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:27]2)[N:18]=[C:17]2[C:13]=1[NH:14][C:15](=[O:25])[N:16]2[CH:19]1[CH2:20][CH2:21][O:22][CH2:23][CH2:24]1

Participants

5

Reactant 2

HCID 9005Trimethyl orthoformateHCID 86622936HCID 86622936, compound

Product 1

HCID 59799574HCID 59799574, compoundYield 73%

Reagents, catalysts & solvents 2

HCID 6395Methanesulfonic AcidCatalystHCID 887MethanolSolvent

Procedure

Pale yellow solid. Synthesized from 2-(2-amino-5-fluorophenylamino)-6-chloro-9-(tetrahydro-2H-pyran-4-yl)-7H-purin-8(9H)-one (160 mg, 0.42 mmol) in anhydrous methanol (10 mL), using anhydrous trimethylorthoformate (1 mL) and methane sulfonic acid (5 drops) with stirring under Ar at room temperature for 2 h (HPLC monitoring). The solvent was removed in vacuo and the residue purified by column chromatography (silica gel, gradual elution with 2% methanol in methylene chloride to 10% methanol in methylene chloride) to afford the desired product (120 mg, 73% yield). 1H NMR (300 MHz, CDCl3+CD3OD) δ, ppm: 9.03 (s, 1H), 8.40-8.20 (m, 1H), 7.82-7.72 (m, 1H), 7.17-7.11 (m, 1H), 4.72-4.58 (m, 1H), 4.28-4.13 (m, 2H), 3.70-3.62 (m, 2H), 2.90-2.72 (m, 2H), 1.90-1.78 (m, 2H); MS (EI) m/z 389.2 (MH)+.

Workup

  1. customThe solvent was removed in vacuo
  2. customthe residue purified by column chromatography (silica gel, gradual elution with 2% methanol in methylene chloride to 10% methanol in methylene chloride)

Sources & evidence

ORD record
ord-5d3c161e802e467b8bb3a0865846d371
Source dataset
uspto-grants-2011_04
Patent number
US07919490B2

Reaction notes

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