Acetic Acid → HCID 178436904, compound

HRID 340023Notes

Reaction equation

HRID 340023 reaction equation
Br.Br.Br.[CH2:4]([C:6]1[C:7]([C:14]2[CH:22]=[C:21]3[C:17]([C:18]([C:23]4[NH:24][C:25]5[CH2:30][CH2:29][NH:28][CH2:27][C:26]=5[N:31]=4)=[N:19][NH:20]3)=[CH:16][CH:15]=2)=[CH:8][C:9]([F:13])=[C:10]([OH:12])[CH:11]=1)[CH3:5].[N:32]1[C:41]2[C:36](=[CH:37][C:38]([CH:42]=O)=[CH:39][CH:40]=2)[CH:35]=[CH:34][CH:33]=1.CCN(C(C)C)C(C)C.CC(O)=O>CN(C=O)C>[CH2:4]([C:6]1[C:7]([C:14]2[CH:22]=[C:21]3[C:17]([C:18]([C:23]4[NH:24][C:25]5[CH2:30][CH2:29][N:28]([CH2:42][C:38]6[CH:37]=[C:36]7[C:41](=[CH:40][CH:39]=6)[N:32]=[CH:33][CH:34]=[CH:35]7)[CH2:27][C:26]=5[N:31]=4)=[N:19][NH:20]3)=[CH:16][CH:15]=2)=[CH:8][C:9]([F:13])=[C:10]([OH:12])[CH:11]=1)[CH3:5]

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 81531DiisopropylethylamineHCID 7656536-QuinolinecarbaldehydeHCID 1784192405-Ethyl-2-fluoro-4-[3-(4,5,6,7-tetrahydro-1H-imidazol[4,5-c]pyridin-2-yl)-1H-indazol-6-yl]-phenol trihydrobromide salt

Product 1

HCID 178436904HCID 178436904, compoundYield 30.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 5-ethyl-2-fluoro-4-[3-(4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridin-2-yl)-1H-indazol-6-yl]-phenol trihydrobromide salt (Preparation 25, 50 mg, 132 μmol) in DMF (1 mL), was added quinoline-6-carbaldehyde (31 mg, 198 μmol), DIPEA (34 mg, 46 μL, 264 μmol) and AcOH (11.8 mg, 11 μL, 198 μmol). The reaction mixture was stirred at room temperature for 1 hour. STAB (42 mg, 198 μmol) was added and stirring was continued for 18 hours. The reaction mixture was partitioned between EtOAc (10 mL) and saturated aqueous sodium hydrogen carbonate solution (10 ml). The organic layer was washed with further saturated aqueous sodium hydrogen carbonate solution (2×10 mL), dried over magnesium sulfate and concentrated in vacuo to furnish a brown oil. The crude material was purified by HPLC Method A to afford 20.6 mg of the title compound.

Workup

  1. additionSTAB (42 mg, 198 μmol) was added
  2. stirringstirring
  3. waitwas continued for 18 hours
  4. customThe reaction mixture was partitioned between EtOAc (10 mL) and saturated aqueous sodium hydrogen carbonate solution (10 ml)
  5. washThe organic layer was washed with further saturated aqueous sodium hydrogen carbonate solution (2×10 mL)
  6. dry with materialdried over magnesium sulfate
  7. concentrationconcentrated in vacuo
  8. customto furnish a brown oil
  9. customThe crude material was purified by HPLC Method A

Sources & evidence

ORD record
ord-da927373f62044589017e7a39ac537ac
Source dataset
uspto-grants-2014_11
Patent number
US08895544B2

Reaction notes

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