Propanal → [5-Fluoro-2-(4-fluorobenzyloxy)pyrimidin-4-yl](1-methoxypropyl)amine

HRID 705568Notes

Reaction equation

HRID 705568 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:18]12([CH2:28]S(O)(=O)=O)C(C)(C)C(CC1)C[C:19]2=[O:20].[CH:33](=O)CC>>[F:1][C:2]1[C:3]([NH:17][CH:19]([O:20][CH3:33])[CH2:18][CH3:28])=[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

4

Reactant 3

HCID 527PropanalHCID 18462Bicyclo[2.2.1]heptane-1-methanesulfonic acid, 7,7-dimethyl-2-oxo-, (1S)-HCID 578185745-Fluoro-2-(4-fluorobenzyloxy)pyrimidin-4-amine

Product 1

HCID 57818741[5-Fluoro-2-(4-fluorobenzyloxy)pyrimidin-4-yl](1-methoxypropyl)amineYield 24%

Procedure

To a solution of 5-fluoro-2-(4-fluorobenzyloxy)pyrimidin-4-ylamine (0.10 g, 0.42 mmol) in propionaldehyde (2 mL) was added a catalytic amount of camphorsulfonic acid. The mixture was agitated on an orbital shaker at room temperature for 4 h and then evaporated to dryness. Methanol (2 mL) was added, and the resulting solution was warmed to 60° C. for 1 h. After evaporation, the crude product was purified by reverse phase chromatography to yield the title compound (0.030 g, 24% yield) as a clear, colorless oil: 1H NMR (300 MHz, CDCl3) δ 7.91 (d, J=2.5 Hz, 1H), 7.47-7.41 (m, 2H), 7.09-7.01 (m, 2H), 5.41 (dt, J=9.9 and 6.0 Hz, 1H), 5.30 (s, 2H), 5.2 (bd, J˜10 Hz, 1H), 3.12 (s, 3H), 1.88-1.60 (m, 2H), 0.98 (t, J=7.1 Hz, 3H). HPLC-MS 308 (ES−), 310 (ES+).

Workup

  1. customevaporated to dryness
  2. additionMethanol (2 mL) was added
  3. temperaturethe resulting solution was warmed to 60° C. for 1 h
  4. customAfter evaporation
  5. customthe crude product was purified by reverse phase chromatography

Sources & evidence

ORD record
ord-101490c3381c401c9f235e3aed05383d
Source dataset
uspto-grants-2015_11
Patent number
US09174970B2

Reaction notes

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