Diisopropylethylamine → (5-Chloro-pyridin-2-yl)-{2-[6-(2-ethyl-5-fluoro-4-hydroxy-phenyl)-1H-indazol-3-yl]-4,5,7,8-tetrahydro-1H-imidazo[4,5-d]azepin-6-yl}-methanone

HRID 2038664Notes

Reaction equation

HRID 2038664 reaction equation
[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]([OH:10])=O)=[N:6][CH:7]=1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.Br.Br.Br.[CH2:38]([C:40]1[C:41]([C:48]2[CH:56]=[C:55]3[C:51]([C:52]([C:57]4[NH:66][C:60]5[CH2:61][CH2:62][NH:63][CH2:64][CH2:65][C:59]=5[N:58]=4)=[N:53][NH:54]3)=[CH:50][CH:49]=2)=[CH:42][C:43]([F:47])=[C:44]([OH:46])[CH:45]=1)[CH3:39].CCN(C(C)C)C(C)C.C(=O)([O-])O.[Na+]>CN(C=O)C>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]([N:63]2[CH2:62][CH2:61][C:60]3[N:66]=[C:57]([C:52]4[C:51]5[C:55](=[CH:56][C:48]([C:41]6[CH:42]=[C:43]([F:47])[C:44]([OH:46])=[CH:45][C:40]=6[CH2:38][CH3:39])=[CH:49][CH:50]=5)[NH:54][N:53]=4)[NH:58][C:59]=3[CH2:65][CH2:64]2)=[O:10])=[N:6][CH:7]=1

Participants

7

Reactant 5

HCID 81531DiisopropylethylamineHCID 516892Sodium BicarbonateHCID 27628725-Chloro-2-picolinic acidHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 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 136263947(5-Chloro-pyridin-2-yl)-{2-[6-(2-ethyl-5-fluoro-4-hydroxy-phenyl)-1H-indazol-3-yl]-4,5,7,8-tetrahydro-1H-imidazo[4,5-d]azepin-6-yl}-methanoneYield 48.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 5-chloro-pyridine-2-carboxylic acid (13.2 mg, 85 μmol) in DMF (1 mL) was added HATU (32 mg, 85 μmol) and the resulting reaction mixture was stirred at room temperature for 30 minutes. 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, 50 mg, 80 μmol) and DIPEA (56 μL, 320 μmol) were added and stirring was continued at room temperature for 18 hours. Saturated aqueous sodium hydrogen carbonate solution (5 mL) was added to the reaction mixture. 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 20.5 mg of the title compound.

Workup

  1. customthe resulting reaction mixture
  2. stirringstirring
  3. waitwas continued at room temperature for 18 hours
  4. filtrationThe resulting solid was collected by filtration
  5. washwashed with further saturated aqueous sodium hydrogen carbonate solution
  6. customThe crude material was purified by HPLC Method A

Sources & evidence

ORD record
ord-ace0d364f8c94559a38ecc97288fb11b
Source dataset
uspto-grants-2013_11
Patent number
US08575336B2

Reaction notes

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