Hydrochloric Acid → N-[5-(3,5-difluoro-benzenesulfonyl)-1H-indazol-3-yl]-4-(4-methyl-piperazin-1-yl)-2-[(tetrahydro-pyran-4-yl)-(2,2,2-trifluoro-acetyl)-amino]-benzamide

HRID 1640990Notes

Reaction equation

HRID 1640990 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([S:9]([C:12]2[CH:13]=[C:14]3[C:18](=[CH:19][CH:20]=2)[N:17](C(C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[N:16]=[C:15]3[NH:40][C:41](=[O:68])[C:42]2[CH:47]=[CH:46][C:45]([N:48]3[CH2:53][CH2:52][N:51]([CH3:54])[CH2:50][CH2:49]3)=[CH:44][C:43]=2[N:55]([CH:62]2[CH2:67][CH2:66][O:65][CH2:64][CH2:63]2)[C:56](=[O:61])[C:57]([F:60])([F:59])[F:58])(=[O:11])=[O:10])[CH:5]=[C:6]([F:8])[CH:7]=1.Cl>O1CCOCC1.CO>[F:8][C:6]1[CH:5]=[C:4]([S:9]([C:12]2[CH:13]=[C:14]3[C:18](=[CH:19][CH:20]=2)[NH:17][N:16]=[C:15]3[NH:40][C:41](=[O:68])[C:42]2[CH:47]=[CH:46][C:45]([N:48]3[CH2:49][CH2:50][N:51]([CH3:54])[CH2:52][CH2:53]3)=[CH:44][C:43]=2[N:55]([CH:62]2[CH2:67][CH2:66][O:65][CH2:64][CH2:63]2)[C:56](=[O:61])[C:57]([F:59])([F:60])[F:58])(=[O:10])=[O:11])[CH:3]=[C:2]([F:1])[CH:7]=1

Participants

5

Reactant 2

HCID 313Hydrochloric AcidHCID 86643843N-[5-(3,5-difluoro-benzenesulfonyl)-1-trityl-1H-indazol-3-yl]-4-(4-methyl-piperazin-1-yl)-2-[(tetrahydro-pyran-4-yl)-(2,2,2-trifluoro-acetyl)-amino]-benzamide

Product 1

HCID 86643844N-[5-(3,5-difluoro-benzenesulfonyl)-1H-indazol-3-yl]-4-(4-methyl-piperazin-1-yl)-2-[(tetrahydro-pyran-4-yl)-(2,2,2-trifluoro-acetyl)-amino]-benzamideYield 80%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 312751,4-DioxaneSolvent2×

Procedure

A mixture of N-[5-(3,5-difluoro-benzenesulfonyl)-1-trityl-1H-indazol-3-yl]-4-(4-methyl-piperazin-1-yl)-2-[(tetrahydro-pyran-4-yl)-(2,2,2-trifluoro-acetyl)-amino]-benzamide (2.4 g, 2.53 mmol), 4N hydrochloric acid in 1,4-dioxane (35 mL), methanol (50 mL) and 1,4-dioxane (15 mL) was stirred at room temperature for 3 hours. The solvents were removed under reduced pressure and the residue dissolved in dichloromethane, washed with water, brine, dried over sodium sulfate and evaporated to dryness. The crude was purified by flash chromatography on silica gel using dichloromethane/acetone 1:1 as the eluant affording the title compound as a pale yellow solid (1.43 g, 80% yield).

Workup

  1. customThe solvents were removed under reduced pressure
  2. dissolutionthe residue dissolved in dichloromethane
  3. washwashed with water, brine
  4. dry with materialdried over sodium sulfate
  5. customevaporated to dryness
  6. customThe crude was purified by flash chromatography on silica gel

Sources & evidence

ORD record
ord-271d8d91ce7f48a6aa4042483d9f611e
Source dataset
uspto-grants-2012_02
Patent number
US08114865B2

Reaction notes

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