Cyclohexylamine → HCID 90229261, compound

HRID 1505768Notes

Reaction equation

HRID 1505768 reaction equation
[F:1][C:2]([F:33])([F:32])[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[C:9]([NH:11][C:12]1[CH:13]=[C:14]2[C:18](=[C:19]([C:21]([OH:23])=O)[CH:20]=1)[N:17]([CH2:24][O:25][CH2:26][CH2:27][Si:28]([CH3:31])([CH3:30])[CH3:29])[N:16]=[CH:15]2)=[O:10].CN(C(O[N:42]1N=N[C:44]2[CH:45]=[CH:46][CH:47]=[CH:48][C:43]1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(CC)CC)C.C1(N)CCCCC1>CN(C=O)C>[CH:43]1([NH:42][C:21]([C:19]2[CH:20]=[C:12]([NH:11][C:9]([C:4]3[CH:5]=[CH:6][CH:7]=[CH:8][C:3]=3[C:2]([F:1])([F:33])[F:32])=[O:10])[CH:13]=[C:14]3[C:18]=2[N:17]([CH2:24][O:25][CH2:26][CH2:27][Si:28]([CH3:30])([CH3:31])[CH3:29])[N:16]=[CH:15]3)=[O:23])[CH2:48][CH2:47][CH2:46][CH2:45][CH2:44]1

Participants

6

Reactant 4

HCID 7965CyclohexylamineHCID 8471TriethylamineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 90229279HCID 90229279, compound

Product 1

HCID 90229261HCID 90229261, compoundYield 105.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 5-({[2-(trifluoromethyl)phenyl]carbonyl}amino)-1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-indazole-7-carboxylic acid (obtained in Step 5) (48 mg) in DMF (2 mL) were added HBTU (46 mg) and triethylamine (17 μL), and the mixture was stirred at room temperature, cyclohexylamine (12.5 μL) was added, and it was stirred at the same temperature overnight. The reaction mixture was poured into ice water, and extracted with ethyl acetate. The ethyl acetate layer was washed sequentially with saturated aqueous sodium bicarbonate and brine, dried over anhydrous magnesium sulfate, and the solvent was removed under reduced pressure. The residue was triturated in n-hexane/ethyl acetate (10:1), and collected by filtration to obtain 59 mg of N-cyclohexyl-5-({[2-(trifluoromethyl)phenyl]carbonyl}amino)-1-[2-(trimethylsilyl)ethoxymethyl]-indazole-7-carboxamide as colorless powder. This was dissolved in MeOH (2 mL), 6N hydrochloric acid (2 mL) was added, and the solution was stirred on oil bath at 60-80° C. for 10 hours. The solvent was removed, and ice water was added to the residue. The precipitate was collected by filtration and dried to obtain the titled compound (33 mg) as colorless powder.

Workup

  1. stirringit was stirred at the same temperature overnight
  2. extractionextracted with ethyl acetate
  3. washThe ethyl acetate layer was washed sequentially with saturated aqueous sodium bicarbonate and brine
  4. dry with materialdried over anhydrous magnesium sulfate
  5. customthe solvent was removed under reduced pressure
  6. customThe residue was triturated in n-hexane/ethyl acetate (10:1)
  7. filtrationcollected by filtration

Sources & evidence

ORD record
ord-72b690a697cb47fa8c6b852a41f0e1d2
Source dataset
uspto-grants-2015_12
Patent number
US09216968B2

Reaction notes

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