Diisopropylethylamine → 5-{2-[6-(2-Ethyl-5-fluoro-4-hydroxy-phenyl)-1H-indazol-3-yl]-4,5,7,8-tetrahydro-1H-imidazo[4,5-d]azepine-6-carbonyl}-pyridine-2-carbonitrile

HRID 340022Notes

Reaction equation

HRID 340022 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:32][C:26]5[CH2:27][CH2:28][NH:29][CH2:30][CH2:31][C:25]=5[N:24]=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].[C:33]([C:35]1[CH:43]=[CH:42][C:38]([C:39](Cl)=[O:40])=[CH:37][N:36]=1)#[N:34].CCN(C(C)C)C(C)C.C(=O)([O-])O.[Na+]>CN(C=O)C>[CH2:4]([C:6]1[CH:11]=[C:10]([OH:12])[C:9]([F:13])=[CH:8][C:7]=1[C:14]1[CH:22]=[C:21]2[C:17]([C:18]([C:23]3[NH:32][C:26]4[CH2:27][CH2:28][N:29]([C:39]([C:38]5[CH:42]=[CH:43][C:35]([C:33]#[N:34])=[N:36][CH:37]=5)=[O:40])[CH2:30][CH2:31][C:25]=4[N:24]=3)=[N:19][NH:20]2)=[CH:16][CH:15]=1)[CH3:5]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 516892Sodium BicarbonateHCID 235126576-Cyanopyridine-3-carbonyl chlorideHCID 1363339625-Ethyl-2-fluoro-4-[3-(1,4,5,6,7,8-hexahydro-imidazo[4,5-d]azepin-2-yl)-1H-indazol-6-yl]-phenol trihydrobromide salt

Product 1

HCID 1362639685-{2-[6-(2-Ethyl-5-fluoro-4-hydroxy-phenyl)-1H-indazol-3-yl]-4,5,7,8-tetrahydro-1H-imidazo[4,5-d]azepine-6-carbonyl}-pyridine-2-carbonitrileYield 44.9%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 5-ethyl-2-fluoro-4-[3-(1,4,5,6,7,8-hexahydro-imidazo[4,5-d]azepin-2-yl)-1H-indazol-6-yl]-phenol trihydrobromide salt (Preparation 32, 28 mg, 44 μmol) in DMF (1 mL), was added 6-cyano-nicotinoyl chloride (Preparation 46, 20.9 mg, 141 μmol), and DIPEA (31 μL, 176 μmol). The reaction mixture was stirred at room temperature for 18 hours and then saturated aqueous sodium hydrogen carbonate solution (5 mL) was added. The resulting solid was collected by filtration and washed with further saturated aqueous sodium hydrogen carbonate solution. The crude material was purified by HPLC Method A to afford 10.3 mg of the title compound.

Workup

  1. filtrationThe resulting solid was collected by filtration
  2. washwashed with further saturated aqueous sodium hydrogen carbonate solution
  3. customThe crude material was purified by HPLC Method A

Sources & evidence

ORD record
ord-22bd1903cac44cba9cab836a7611d384
Source dataset
uspto-grants-2014_11
Patent number
US08895544B2

Reaction notes

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