5-Fluoro-2-(4-fluorobenzyloxy)pyrimidin-4-amine → HCID 178512304, compound

HRID 705575Notes

Reaction equation

HRID 705575 reaction equation
[F:1][C:2]1[C:3]([NH2:17])=[N:4][C:5]([O:8][CH2:9][C:10]2[CH:15]=[CH:14][C:13]([F:16])=[CH:12][CH:11]=2)=[N:6][CH:7]=1>C(Cl)(Cl)Cl>[F:1][C:2]1[C:3]([NH:17][CH:5]=[N:4][C:3]#[N:17])=[N:4][C:5]([O:8][CH2:9][C:10]2[CH:11]=[CH:12][C:13]([F:16])=[CH:14][CH:15]=2)=[N:6][CH:7]=1

Participants

3

Reactant 1

HCID 578185745-Fluoro-2-(4-fluorobenzyloxy)pyrimidin-4-amine

Product 1

HCID 178512304HCID 178512304, compoundYield 183.2%

Reagents, catalysts & solvents 1

HCID 6212ChloroformSolvent

Conditions

Temperature
90 °C

Procedure

Cyanamide (8.00 g, 190.0 mmol) was stirred at reflux in triethylorthoformate (60 mL) for 2 h. The reaction was cooled to room temperature and distilled to provide ethyl-N-cyanoimidate (12.5 g, bp=110-112° C./45 mm Hg).* To this imidate (1 mL) was added 5-fluoro-2-(4-fluorobenzyloxy)pyrimidin-4-ylamine (0.05 g, 0.2 mmol) and the mixture was heated at 90° C. for 4 h, cooled, diluted with chloroform, filtered, and evaporated. The crude product was purified by reverse phase chromatography to furnish 0.053 g (17%) of the title compound as an off white solid: mp 148-149° C.; 1H NMR (300 MHz, CDCl3) δ 9.45 and 9.33 (bd, bs, J≈10 Hz, 1H), 8.33 and 8.25 (2d, J≈2 Hz, 1H), 7.46-7.38 (m, 2H), 7.11-7.01 (m, 2H), 5.35 and 5.33 (2s, 2H); HPLC-MS (ESI) m/z 290 (M+H)+, 288 (M−H)−. * Bridsen, Peter K., and Wang, Xiaodong, Synthesis, 1995, 855-8.

Workup

  1. temperaturecooled
  2. filtrationfiltered
  3. customevaporated
  4. customThe crude product was purified by reverse phase chromatography

Sources & evidence

ORD record
ord-73f8ac6e36bb402abb56fe5bcc3946af
Source dataset
uspto-grants-2015_11
Patent number
US09174970B2

Reaction notes

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