Acetic Acid → 3-[4-(4-Fluoro-phenyl)-5-methyl-pyrimidin-2-yl]-benzoic acid

HRID 628831Notes

Reaction equation

HRID 628831 reaction equation
CN(C)[CH2:3][CH2:4][C:5]([C:7]1[CH:12]=[CH:11][C:10]([F:13])=[CH:9][CH:8]=1)=O.C([O:19][C:20](=[O:30])[C:21]1[CH:26]=[CH:25][CH:24]=[C:23]([C:27](=[NH:29])[NH2:28])[CH:22]=1)(C)(C)C.[C:31](O)(=O)C>>[F:13][C:10]1[CH:11]=[CH:12][C:7]([C:5]2[C:4]([CH3:31])=[CH:3][N:28]=[C:27]([C:23]3[CH:22]=[C:21]([CH:26]=[CH:25][CH:24]=3)[C:20]([OH:19])=[O:30])[N:29]=2)=[CH:8][CH:9]=1

Participants

4

Reactant 3

HCID 176Acetic AcidHCID 4159943-Dimethylamino-1-(4-fluoro-phenyl)-propan-1-oneHCID 692347943-Carbamimidoyl-benzoic acid tert-butyl ester

Product 1

HCID 116739533-[4-(4-Fluoro-phenyl)-5-methyl-pyrimidin-2-yl]-benzoic acidYield 12%

Conditions

Temperature
130 °C

Procedure

Part B. A mixture of 3-dimethylamino-1-(4-fluoro-phenyl)-propan-1-one (641.9 mg, 3.10 mmol) and 3-carbamimidoyl-benzoic acid tert-butyl ester (426.1 mg, 1.91 mmol) in anhydrous acetic acid (8 mL) is heated to 130° C. at 300 W, 250 psi in a microwave reactor for 30 min. A white solid is precipitated by addition of 1 N HCl, and collected by filtration, followed by washing with water and hexanes. The obtained solid is further purified by flash column chromatography, eluting with methanol/methylene chloride (1:40) to afford the title product (114.1 mg, 12.0% yield), m.p. 272-275° C. 1H NMR (300 MHz, DMSO-d6): δ 8.50 (2H, d, J=8.0 Hz), 8.06 (2H, d, J=8.0 Hz), 7.85 (2H, m), 8.13 (2H, m), 7.38 (2H, m), 2.40 (3H, s). MS (ES+): m/e 309.34.

Workup

  1. customA white solid is precipitated by addition of 1 N HCl
  2. filtrationcollected by filtration
  3. washby washing with water and hexanes
  4. customThe obtained solid is further purified by flash column chromatography
  5. washeluting with methanol/methylene chloride (1:40)

Sources & evidence

ORD record
ord-c7db3f23eec847cfa6be2d95bd0e2a92
Source dataset
uspto-grants-2016_04
Patent number
US09315467B2

Reaction notes

Loading…