Triethylamine → 3-[3-(2,5-difluorophenyl)-1-(morpholin-4-ylcarbonyl)-5-phenyl-4,5-dihydro-1H-pyrazol-5-yl]propan-1-amine

HRID 20611Notes

Reaction equation

HRID 20611 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([F:8])=[CH:4][C:3]=1[C:9]1[CH2:13][C:12]([CH2:20][CH2:21][CH2:22]O)([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[N:11]([C:24]([N:26]2[CH2:31][CH2:30][O:29][CH2:28][CH2:27]2)=[O:25])[N:10]=1.C([N:34](CC)CC)C.S(Cl)(C)(=O)=O.C([O-])(O)=O.[Na+].[N-]=[N+]=[N-].[Na+].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>C(Cl)Cl.[Cl-].[Na+].O.CCOC(C)=O.O>[F:1][C:2]1[CH:7]=[CH:6][C:5]([F:8])=[CH:4][C:3]=1[C:9]1[CH2:13][C:12]([CH2:20][CH2:21][CH2:22][NH2:34])([C:14]2[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=2)[N:11]([C:24]([N:26]2[CH2:31][CH2:30][O:29][CH2:28][CH2:27]2)=[O:25])[N:10]=1

Participants

11

Reactant 6

HCID 8471TriethylamineHCID 11776TriphenylphosphineHCID 31297Methanesulfonyl chlorideHCID 33557Sodium AzideHCID 516892Sodium BicarbonateHCID 687180813-[3-(2,5-difluorophenyl)-1-(morpholin-4-ylcarbonyl)-5-phenyl-4,5-dihydro-1H-pyrazol-5-yl]propan-1-ol

Product 1

HCID 102381263-[3-(2,5-difluorophenyl)-1-(morpholin-4-ylcarbonyl)-5-phenyl-4,5-dihydro-1H-pyrazol-5-yl]propan-1-amine

Reagents, catalysts & solvents 4

HCID 962WaterSolventHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolventHCID 57417360Sodium chloride; waterSolvent2×

Conditions

Temperature
65 °C

Procedure

To 268 mg (0.62 mmol) of 7-6 in CH2Cl2 was added 175 μL (1.24 mmol) of triethylamine and 75 mL (0.93 mmol) of mesyl chloride. After stirring for 1 h, the mixture was dumped into a separatory funnel with saturated NaHCO3, extracted twice with CH2Cl2, washed with water, and dried over Na2SO4. The residue was dissolved in DMF, 82 mg (1.24 mmol) of sodium azide was added, and the reaction was heated for 4 h at 65° C. After cooling to rt, the mixture was dumped into brine, extracted twice with EtOAc, and then washed with brine. The organic layer was dried over Na2SO4, concentrated, redissolved in THF and 205 mg (0.78 mmol) of triphenylphosphine was added. After stirring for 15 h, 1 mL of water was added and the mixture was heated at 65° C. for 1 h. The reaction was worked up with EtOAc and brine, dried over Na2SO4, concentrated, and purified by column chromatography on silica gel with CH2Cl2/MeOH/TEA to provide 7-7 as a white solid. Data for 7-7: 1HNMR (500 MHz, CDCl3) δ 7.5 (m, 1H), 7.4-7.2 (m, 5H), 7.1-7.0 (m, 2H), 3.8-3.6 (m, 4H), 3.6 (m, 4H), 3.5 (m, 1H), 3.4 (m, 1H), 2.9-2.8 (m, 3H), 2.2 (m, 1H), 1.6 (m, 2H) ppm. HRMS (ES) calc'd M+Na for C23H26F2N4O2: 429.2097. Found: 429.2097.

Workup

  1. extractionextracted twice with CH2Cl2
  2. washwashed with water
  3. dry with materialdried over Na2SO4
  4. dissolutionThe residue was dissolved in DMF
  5. temperatureAfter cooling to rt
  6. extractionextracted twice with EtOAc
  7. washwashed with brine
  8. dry with materialThe organic layer was dried over Na2SO4
  9. concentrationconcentrated
  10. dissolutionredissolved in THF
  11. stirringAfter stirring for 15 h
  12. temperaturethe mixture was heated at 65° C. for 1 h
  13. dry with materialdried over Na2SO4
  14. concentrationconcentrated
  15. custompurified by column chromatography on silica gel with CH2Cl2/MeOH/TEA

Sources & evidence

ORD record
ord-a8cedd292fe4469aaa1ef66008b66607
Source dataset
uspto-grants-2010_06
Patent number
US07745639B2

Reaction notes

Loading…