Thionyl Chloride → HCID 15547420, compound

HRID 1385092Notes

Reaction equation

HRID 1385092 reaction equation
S(Cl)(Cl)=O.[CH:5]1([N:10]2[C:18]3[C:13](=[CH:14][CH:15]=[C:16]([C:19]([OH:21])=O)[CH:17]=3)[C:12]([CH2:22][CH3:23])=[N:11]2)[CH2:9][CH2:8][CH2:7][CH2:6]1.[H-].[Na+].[NH2:26][C:27]1[C:28]([Cl:34])=[N:29][CH:30]=[N:31][C:32]=1[Cl:33]>C1(C)C=CC=CC=1.CN(C=O)C.C(OCC)(=O)C>[Cl:34][C:28]1[C:27]([NH:26][C:19]([C:16]2[CH:17]=[C:18]3[C:13]([C:12]([CH2:22][CH3:23])=[N:11][N:10]3[CH:5]3[CH2:6][CH2:7][CH2:8][CH2:9]3)=[CH:14][CH:15]=2)=[O:21])=[C:32]([Cl:33])[N:31]=[CH:30][N:29]=1

Participants

8

Reactant 4

HCID 24386Thionyl ChlorideHCID 24758Sodium hydrideHCID 794345-Amino-4,6-dichloropyrimidineHCID 15545851HCID 15545851, compound

Product 1

HCID 15547420HCID 15547420, compoundYield 15%

Reagents, catalysts & solvents 3

HCID 1140TolueneSolventHCID 6228DimethylformamideSolvent3×HCID 8857Ethyl AcetateSolvent

Procedure

50 μL (0.680 mmol, 1.3 equiv) thionyl chloride were added to a room temperature solution of 135 mg (0.523 mmol, 1.0 equiv) 1-cyclopentyl-3-ethyl-1h-indazole-6-carboxylic acid and 10 μL DMF in 5 mL anhydrous toluene. The reaction mixture was heated to reflux for 2 hours, then cooled to room temperature, concentrated to dryness on a rotary evaporator, and dried at high vacuum, room temperature for several hours. 21 mg (0.523 mmol, 1.0 equiv) sodium hydride, 60% oil dispersion, were added to a separate flask containing a room temperature solution of 86 mg (0.523 mmol, 1.0 equiv) 5-amino-4,6-dichloro-pyrimidine in 5 mL anhydrous DMF. After 10 minutes, a solution of the acid chloride (prepared above) in 5 mL anhydrous DMF was added, and the mixture stirred for 24 hours at room temperature. The reaction mixture was then heated to 70° C. for 1.5 hours, cooled to room temperature, diluted with 75 mL ethyl acetate, washed 2×15 mL H2O, 1×16 mL brine, and dried over MgSO4. The crude product was purified on a silica gel column (20 % ethyl acetate/hexanes) to give 31 mg (15%) of white crystalline solid: mp 171-172° C.; Anal. calcd for C19H19N5OCl2: C, 56.44; H, 4.74; N, 17.32. Found: C, 56.38; H, 4.76; N, 17.33.

Workup

  1. temperatureThe reaction mixture was heated
  2. temperatureto reflux for 2 hours
  3. concentrationconcentrated to dryness on a rotary evaporator
  4. customdried at high vacuum, room temperature for several hours
  5. temperatureThe reaction mixture was then heated to 70° C. for 1.5 hours
  6. temperaturecooled to room temperature
  7. washwashed 2×15 mL H2O, 1×16 mL brine
  8. dry with materialdried over MgSO4
  9. customThe crude product was purified on a silica gel column (20 % ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-97cabb73efab4823887ee597c29e3a8e
Source dataset
uspto-grants-2001_07
Patent number
US06262040B1

Reaction notes

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