Trifluoroacetic acid → 6-(4-Hydroxy-3-methoxy-5-methylaminomethyl-phenyl)-4-(1H-indol-2-yl)-2H-pyridazin-3-one

HRID 2234141Notes

Reaction equation

HRID 2234141 reaction equation
C(OC([N:8]1[C:16]2[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=2)[CH:10]=[C:9]1[C:17]1[CH:22]=[C:21]([C:23]2[CH:28]=[C:27]([CH2:29][NH:30][CH3:31])[C:26]([O:32]COCC[Si](C)(C)C)=[C:25]([O:41][CH3:42])[CH:24]=2)[N:20]=[N:19][C:18]=1[O:43]C)=O)(C)(C)C.FC(F)(F)C(O)=O>ClCCl>[OH:32][C:26]1[C:27]([CH2:29][NH:30][CH3:31])=[CH:28][C:23]([C:21]2[CH:22]=[C:17]([C:9]3[NH:8][C:16]4[C:11]([CH:10]=3)=[CH:12][CH:13]=[CH:14][CH:15]=4)[C:18](=[O:43])[NH:19][N:20]=2)=[CH:24][C:25]=1[O:41][CH3:42]

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 686384962-{3-Methoxy-6-[3-methoxy-5-methylaminomethyl-4-(2-trimethylsilanyl-ethoxymethoxy)-phenyl]-pyridazin-4-yl}-indole-1-carboxylic acid tert-butyl ester

Product 1

HCID 1355131436-(4-Hydroxy-3-methoxy-5-methylaminomethyl-phenyl)-4-(1H-indol-2-yl)-2H-pyridazin-3-one

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
85 °C

Procedure

118 mg of 2-{3-Methoxy-6-[3-methoxy-5-methylaminomethyl-4-(2-trimethylsilanyl-ethoxymethoxy)-phenyl]-pyridazin-4-yl}-indole-1-carboxylic acid tert-butyl ester is dissolved in 5 ml of dichloromethane and 5 ml of trifluoroacetic acid and the solution is stirred for 4 h at RT. The solvents are removed under reduced pressure. The residue is dissolved in 26 ml of acetonitrile and 117 mg of potassium iodide and 76 mg of chlorotrimethylsilane are added. The reaction is heated to 85° C. for 3 h. The reaction is quenched by the addition of a drop of water, the solvent is removed under reduced pressure and the product is purified by preparative RP-HPLC eluting with a gradient of 0-100% acetonitrile in water (+0.01% trifluoroacetic acid). Yield 13 mg. LC-MS (ES+) 377 (M+H)+.

Workup

  1. customThe solvents are removed under reduced pressure
  2. dissolutionThe residue is dissolved in 26 ml of acetonitrile
  3. addition117 mg of potassium iodide and 76 mg of chlorotrimethylsilane are added
  4. customThe reaction is quenched by the addition of a drop of water
  5. customthe solvent is removed under reduced pressure
  6. customthe product is purified by preparative RP-HPLC
  7. washeluting with a gradient of 0-100% acetonitrile in water (+0.01% trifluoroacetic acid)

Sources & evidence

ORD record
ord-03fa61cdec1b4e5e9a5c2ed3bb883f33
Source dataset
uspto-grants-2010_05
Patent number
US07709466B2

Reaction notes

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