Triethylamine → HCID 57721368, compound

HRID 1986098Notes

Reaction equation

HRID 1986098 reaction equation
[Cl:1][C:2]1[N:10]=[C:9]([CH3:11])[CH:8]=[CH:7][C:3]=1[C:4]([OH:6])=O.C(Cl)(=O)C(Cl)=O.[F:18][C:19]1[CH:24]=[C:23]([F:25])[CH:22]=[CH:21][C:20]=1[NH2:26].C(N(CC)CC)C>C(Cl)Cl.CN(C=O)C>[Cl:1][C:2]1[N:10]=[C:9]([CH3:11])[CH:8]=[CH:7][C:3]=1[C:4]([NH:26][C:20]1[CH:21]=[CH:22][C:23]([F:25])=[CH:24][C:19]=1[F:18])=[O:6]

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 97092,4-DifluoroanilineHCID 65578Oxalyl chlorideHCID 1217242-Chloro-6-methylnicotinic acid

Product 1

HCID 57721368HCID 57721368, compoundYield 68.2%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideCatalystHCID 6344DichloromethaneSolvent

Conditions

Temperature
23 °C

Procedure

2-Chloro-6-methylnicotinic acid (500 mg, 2.9 mmol) was suspended in CH2Cl2 (14.6 mL). Oxalyl chloride (0.3 mL, 3.5 mmol) was added followed by 3 drops of DMF and the reaction was stirred at 23° C. for 2 h. The solvent was removed by rotary evaporation and the residue was dried under vacuum. The crude acid chloride was dissolved in CH3CN (14 mL) and 2,4-difluorobenzenamine (0.33 mL, 3.2 mmol) was added followed by triethylamine (0.41 mL, 2.9 mmol). The reaction was stirred at 23° C. for 16 h and then concentrated in vacuo. The residue was partitioned between EtOAc (30 mL) and sat. aq. NaHCO3 soln (30 mL). A little water was added to help break up some of the residual salts. The aqueous layer was extracted with EtOAc (3×30 mL). The combined organics were dried over MgSO4 and concentrated in vacuo. Trituration with hot 5% EtOAc-hexanes afforded the desired product as a light tan powder (559 mg, 68%). 1H NMR (400 MHz, CDCl3) δ 2.60 (s, 3H), 6.82-7.09 (m, 2H), 7.22-7.32 (d, 1H, J=7.63 Hz), 8.18 (d, 1H, J=8.14 Hz), 8.28-8.50 (m, 1H), 8.57 (s, 1H).

Workup

  1. customThe solvent was removed by rotary evaporation
  2. customthe residue was dried under vacuum
  3. dissolutionThe crude acid chloride was dissolved in CH3CN (14 mL)
  4. stirringThe reaction was stirred at 23° C. for 16 h
  5. concentrationconcentrated in vacuo
  6. customThe residue was partitioned between EtOAc (30 mL) and sat. aq. NaHCO3 soln (30 mL)
  7. additionA little water was added
  8. extractionThe aqueous layer was extracted with EtOAc (3×30 mL)
  9. dry with materialThe combined organics were dried over MgSO4
  10. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-a5e6625414034386b7dfae5f1d90350b
Source dataset
uspto-grants-2009_06
Patent number
US07547782B2

Reaction notes

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