Tetrahydrofuran → 2-[4-(4-Fluorophenoxy)phenyl]pyrimidine-4-carboxamide

HRID 984058Notes

Reaction equation

HRID 984058 reaction equation
FC1C=CC(OC2C=C[C:10]([C:13]3[N:18]=C(C)C=CN=3)=[CH:9][CH:8]=2)=CC=1.CC(C)([O-:25])C.[K+].C1COCC1.C(O)(=O)C.[F:37][C:38]1[CH:53]=[CH:52][C:41]([O:42][C:43]2[CH:51]=[CH:50][C:46]([C:47]([NH2:49])=[NH:48])=[CH:45][CH:44]=2)=[CH:40][CH:39]=1.COC(OC)CC(=O)C>CN(C=O)C>[F:37][C:38]1[CH:39]=[CH:40][C:41]([O:42][C:43]2[CH:51]=[CH:50][C:46]([C:47]3[N:49]=[C:10]([C:13]([NH2:18])=[O:25])[CH:9]=[CH:8][N:48]=3)=[CH:45][CH:44]=2)=[CH:52][CH:53]=1

Participants

7

Reactant 5

HCID 8028TetrahydrofuranHCID 2285484,4-Dimethoxy-2-butanoneHCID 99655052-[4-(4-Fluorophenoxy)phenyl]-4-methylpyrimidineHCID 23665647Potassium tert-butoxideHCID 685220074-(4-Fluorophenoxy)benzamidine acetate

Product 1

HCID 98362702-[4-(4-Fluorophenoxy)phenyl]pyrimidine-4-carboxamide

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

2-[4-(4-Fluorophenoxy)phenyl]-4-methylpyrimidine: A 1M solution of potassium tert-butoxide in THF (11 mL, 11 mmol) was added via syringe to a solution of 4-(4-fluorophenoxy)benzamidine acetate (2.92 g, 10.2 mmol) in DMF. The resulting mixture was heated at 100° C. for 2 hours. Acetylacetaldehyde dimethyl acetal (2 mL, 13.6 mmol) was added via syringe. The reaction was maintained between 100°-110° C. overnight when TLC indicated complete reaction. The reaction was allowed to cool to room temperature and partitioned between water and EtOAc. The aqueous layer was extracted with EtOAc and the combined organic layers were washed with water (3 times), dried over MgSO4, filtered, and evaporated under reduced pressure to give the desired product as a yellow oil. 1H NMR (CDCl3): δ8.60 (d, J=5.1, 1H), 8.40 (d, J=9.0, 2H), 7.05-7.00 (m, 7H), 2.57 (s, 3H). This material was carried on without further purification.

Workup

  1. temperatureThe reaction was maintained between 100°-110° C. overnight when TLC
  2. customreaction
  3. temperatureto cool to room temperature
  4. custompartitioned between water and EtOAc
  5. extractionThe aqueous layer was extracted with EtOAc
  6. washthe combined organic layers were washed with water (3 times)
  7. dry with materialdried over MgSO4
  8. filtrationfiltered
  9. customevaporated under reduced pressure

Sources & evidence

ORD record
ord-8d720f4f29784f4684d127496d26e028
Source dataset
uspto-grants-2005_03
Patent number
US06867210B2

Reaction notes

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