Diisopropylethylamine → HCID 178522482, compound

HRID 2098242Notes

Reaction equation

HRID 2098242 reaction equation
[Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[N:6]([CH:8]=[C:9]([C:11]([OH:13])=O)[N:10]=2)[N:7]=1.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C.Br.[Cl:48][C:49]1[CH:50]=[C:51]([C:56]2[CH:65]=[CH:64][C:59]3[NH:60][C:61]([NH2:63])=[N:62][C:58]=3[CH:57]=2)[CH:52]=[C:53]([F:55])[CH:54]=1.C(=O)(O)[O-].[Na+]>CN(C=O)C>[Cl:48][C:49]1[CH:50]=[C:51]([C:56]2[CH:65]=[CH:64][C:59]3[NH:60][C:61]([NH:63][C:11]([C:9]4[N:10]=[C:5]5[CH:4]=[CH:3][C:2]([Cl:1])=[N:7][N:6]5[CH:8]=4)=[O:13])=[N:62][C:58]=3[CH:57]=2)[CH:52]=[C:53]([F:55])[CH:54]=1

Participants

7

Reactant 5

HCID 81531DiisopropylethylamineHCID 516892Sodium BicarbonateHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 27946376-Chloroimidazo[1,2-b]pyridazine-2-carboxylic acidHCID 178419693HCID 178419693, compound

Product 1

HCID 178522482HCID 178522482, compoundYield 98.7%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A mixture of 6-chloro-imidazo[1,2-b]pyridazine-2-carboxylic acid (2.5 g), HBTU (4.41 g) and DIEA (4.0 mL) in DMF (20 mL) were stirred at room temperature for 10 minutes. To this reaction mixture was added 5-(3-chloro-5-fluoro-phenyl)-1H-benzoimidazol-2-ylamine hydrobromide salt (3.46 g), and the mixture was heated at 80° C. for 30 minutes. After cooling the reaction mixture to room temperature, an aqueous sodium bicarbonate solution (200 mL) was added, and the mixture was stirred for 30 minutes. The mixture was then filtered, washed with water, dried, and purified on a 80 g pre-packaged silica gel column with a gradient of 0 to 10% 2 M ammonia-methanol in DCM. 4.4 g of 6-chloro-imidazo[1,2-b]pyridazine-2-carboxylic acid [5-(3-chloro-5-fluoro-phenyl)-1H-benzoimidazol-2-yl]-amide was obtained. LCMS (m/z): 441.9. 1H NMR (400 MHz, DMSO-d6) δ 12.18 (2H, br. s.) 9.08 (1H, s) 8.32-8.39 (1H, m) 7.82 (1H, s) 7.46-7.64 (6H, m).

Workup

  1. temperaturethe mixture was heated at 80° C. for 30 minutes
  2. temperatureAfter cooling the reaction mixture to room temperature
  3. stirringthe mixture was stirred for 30 minutes
  4. filtrationThe mixture was then filtered
  5. washwashed with water
  6. customdried
  7. custompurified on a 80 g pre-packaged silica gel column with a gradient of 0 to 10% 2 M ammonia-methanol in DCM

Sources & evidence

ORD record
ord-cffb159577c14432b34a336656faf5bd
Source dataset
uspto-grants-2013_05
Patent number
US08450354B2

Reaction notes

Loading…