Dimethylformamide → HCID 69932817, compound

HRID 540799Notes

Reaction equation

HRID 540799 reaction equation
[F:1][C:2]([F:34])([F:33])[C:3]1[CH:32]=[CH:31][C:6]([O:7][C:8]2[NH:12][N:11]=[C:10]([C:13]3[CH:14]=[C:15]([C:19]4([NH:23][C:24](=[O:30])[O:25][C:26]([CH3:29])([CH3:28])[CH3:27])[CH2:22][O:21][CH2:20]4)[CH:16]=[CH:17][CH:18]=3)[CH:9]=2)=[CH:5][CH:4]=1.Cl[CH2:36][C:37]1[N:38]=[CH:39][O:40][CH:41]=1.[C:42]([O-:45])([O-])=[O:43].[K+].[K+].[CH3:48]N(C=O)C>C(Cl)Cl>[F:34][C:2]([F:1])([F:33])[C:3]1[CH:32]=[CH:31][C:6]([O:7][C:8]2[CH:9]=[C:10]([C:13]3[CH:18]=[CH:17][CH:16]=[C:15]([C:19]4([NH:23][C:24]([O:25][C:26]([CH3:28])([CH3:29])[CH3:27])=[O:30])[CH2:22][O:21][CH2:20]4)[CH:14]=3)[N:11]([CH2:48][C:42]([O:45][CH2:36][CH3:37])=[O:43])[N:12]=2)=[CH:5][CH:4]=1.[F:34][C:2]([F:1])([F:33])[C:3]1[CH:32]=[CH:31][C:6]([O:7][C:8]2[N:12]([CH2:36][C:37]3[N:38]=[CH:39][O:40][CH:41]=3)[N:11]=[C:10]([C:13]3[CH:14]=[C:15]([C:19]4([NH:23][C:24](=[O:30])[O:25][C:26]([CH3:28])([CH3:29])[CH3:27])[CH2:22][O:21][CH2:20]4)[CH:16]=[CH:17][CH:18]=3)[CH:9]=2)=[CH:5][CH:4]=1

Participants

7

Reactant 4

HCID 6228DimethylformamideHCID 11430Potassium CarbonateHCID 216981614-(Chloromethyl)-1,3-oxazoleHCID 178452606HCID 178452606, compound

Product 2

HCID 69932817HCID 69932817, compoundHCID 69933203HCID 69933203, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
100 °C

Procedure

tert-Butyl {3-[3-(5-(4-trifluoromethylphenoxy)-1H-pyrazol-3-yl)phenyl]oxetan-3-yl}carbamate from Example 130, Step 7 (120 mg, 0.25 mmol), 4-chloromethyloxazole (119 mg, 1.0 mmol), and K2CO3 (155 mg, 1.1 mmol) in 0.6 mL of DMF were combined in a sealed tube and the stirred mixture was heated to 100° C. for 18 h. The mixture was cooled to ambient temperature and diluted with CH2Cl2. The mixture was washed with water and brine, then dried over Na2SO4, filtered, and the solvents were reduced under reduced pressure to give an oil. The residue was purified on a C18 column using a gradient elution of 20-100% CH3CN:H2O with 0.1% TFA. Fractions containing the first eluting peak were combined and the solvents were removed under reduced pressure to give compound A, tert-butyl (3-{3-[5-(4-trifluoromethylphenoxy)-1-(1,3-oxazol-4-ylmethyl)-1H-pyrazol-3-yl]phenyl}oxetan-3-yl)carbamate, as a glass. Calcd 557.5. found: 557.8. 1H NMR (400 MHz, CDCl3) δ 7.88 (br s, 1H), 7.65 (m, 3H), 7.50 (d, J=7, 1H), 7.41 (t, J=7, 1H), 7.25 (d, J=7, 2H), 7.08 (s, 1H), 6.06 (s, 1H), 5.45 (s, 2H), 5.01 (br s, 2H), 4.89 (br d, 2H), 1.20 (br s, 9H). Fractions containing the second eluting peak were combined and the solvents were removed under reduced pressure to give compound B, tert-butyl (3-{3-[3-(4-trifluoromethylphenoxy)-1-(1,3-oxazol-4-ylmethyl)-1H-pyrazol-5-yl]phenyl}oxetan-3-yl)carbamate, as a glass. Calcd (M+1)+: 557.5. found: 557.9. 1H NMR (400 MHz, CDCl3) δ 7.45-7.775 (m, 6H), 7.25 (d, J=7, 2H), 7.16 (s, 1H), 5.98 (s, 1H), 5.85 (s, 2H), 4.99 (br 5, 2H), 4.87 (br d, 2H), 1.20 (br s, 9H).

Workup

  1. temperatureThe mixture was cooled to ambient temperature
  2. washThe mixture was washed with water and brine
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. customto give an oil
  6. customThe residue was purified on a C18 column
  7. washa gradient elution of 20-100% CH3CN
  8. additionFractions containing the first eluting peak
  9. customthe solvents were removed under reduced pressure

Sources & evidence

ORD record
ord-c7e545716fd546cc8e8e90558eab34ce
Source dataset
uspto-grants-2014_10
Patent number
US08871796B2

Reaction notes

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