Thionyl Chloride → HCID 86647620, compound

HRID 1773388Notes

Reaction equation

HRID 1773388 reaction equation
[F:1][C:2]1[CH:10]=[CH:9][C:8]([CH:11]=[O:12])=[CH:7][C:3]=1[C:4]([OH:6])=O.S(Cl)(Cl)=O.[F:17][C:18]1[CH:19]=[C:20]([CH:51]=[C:52]([F:54])[CH:53]=1)[CH2:21][C:22]1[CH:23]=[C:24]2[C:28](=[CH:29][CH:30]=1)[N:27]([C:31]([C:44]1[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=1)([C:38]1[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=1)[C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1)[N:26]=[C:25]2[NH2:50].CCN(C(C)C)C(C)C>C1(C)C=CC=CC=1.C1COCC1>[F:17][C:18]1[CH:19]=[C:20]([CH:51]=[C:52]([F:54])[CH:53]=1)[CH2:21][C:22]1[CH:23]=[C:24]2[C:28](=[CH:29][CH:30]=1)[N:27]([C:31]([C:44]1[CH:45]=[CH:46][CH:47]=[CH:48][CH:49]=1)([C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1)[C:38]1[CH:39]=[CH:40][CH:41]=[CH:42][CH:43]=1)[N:26]=[C:25]2[NH:50][C:4](=[O:6])[C:3]1[CH:7]=[C:8]([CH:11]=[O:12])[CH:9]=[CH:10][C:2]=1[F:1]

Participants

7

Reactant 4

HCID 24386Thionyl ChlorideHCID 81531DiisopropylethylamineHCID 185259462-Fluoro-5-formylbenzoic acidHCID 68671320HCID 68671320, compound

Product 1

HCID 86647620HCID 86647620, compoundYield 79%

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
4 °C

Procedure

2-Fluoro-5-formyl-benzoic acid (368 mg, 2.187 mmol) in toluene (22 mL) was treated with thionyl chloride (1.59 mL, 21.87 mmol) and stirred under reflux temperature for 4 hours. The volatiles were evaporated, the residue was taken up with toluene (4 mL) and evaporated to dryness leaving an off white solid which was dissolved in dry THF (5 mL) and added drop-wise to a solution of 5-(3,5-difluoro-benzyl)-1-trityl-1H-indazol-3-ylamine (843 mg, 1.68 mmol) and DIPEA (0.88 mL, 5.04 mmol) in THF (10 mL), cooled to 4° C. The reaction was gradually brought to room temperature. After one night, the volatiles were evaporated. The crude was dissolved in DCM (150 mL) and washed with aqueous NaHCO3 (100 mL) then with water and finally with brine. After drying over sodium sulphate, evaporation and purification over silica gel (eluent: DCM) 868 mg of title compound as a white solid in 79% yield were obtained.

Workup

  1. temperatureunder reflux temperature for 4 hours
  2. customThe volatiles were evaporated
  3. customevaporated to dryness
  4. customleaving an off white solid which
  5. customwas gradually brought to room temperature
  6. waitAfter one night
  7. customthe volatiles were evaporated
  8. dissolutionThe crude was dissolved in DCM (150 mL)
  9. washwashed with aqueous NaHCO3 (100 mL)
  10. dry with materialAfter drying over sodium sulphate, evaporation and purification over silica gel (eluent: DCM) 868 mg of title compound as a white solid in 79% yield
  11. customwere obtained

Sources & evidence

ORD record
ord-347782d7f3dc45b0aced31099ab12ba5
Source dataset
uspto-grants-2016_02
Patent number
US09255087B2

Reaction notes

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