Diisopropylethylamine → HCID 178522480, compound

HRID 2098245Notes

Reaction equation

HRID 2098245 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.[F:48][C:49]([F:68])([F:67])[O:50][C:51]1[CH:52]=[C:53]([C:57]2[CH:66]=[CH:65][C:60]3[NH:61][C:62]([NH2:64])=[N:63][C:59]=3[CH:58]=2)[CH:54]=[CH:55][CH:56]=1.C(=O)(O)[O-].[Na+]>CN(C=O)C>[F:68][C:49]([F:48])([F:67])[O:50][C:51]1[CH:52]=[C:53]([C:57]2[CH:66]=[CH:65][C:60]3[NH:61][C:62]([NH:64][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:63][C:59]=3[CH:58]=2)[CH:54]=[CH:55][CH:56]=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 178419692HCID 178419692, compound

Product 1

HCID 178522480HCID 178522480, compoundYield 98.4%

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-trifluoromethoxy-phenyl)-1H-benzoimidazol-2-ylamine hydrobromide salt (3.78 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 an 80 g pre-packaged silica gel column with a gradient of 0 to 10% 2M ammonia-methanol in DCM. 4.7 g of 6-chloro-imidazo[1,2-b]pyridazine-2-carboxylic acid [5-(3-trifluoromethoxy-phenyl)-1H-benzoimidazol-2-yl]-amide was obtained. LCMS (m/z): 473.9. 1H NMR (400 MHz, DMSO-d6) δ 12.14 (2H, br. s.) 9.08 (1H, s) 8.35 (1H, d) 7.81 (1H, s) 7.73 (1H, d) 7.47-7.65 (5H, m) 7.34 (1H, d).

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 an 80 g pre-packaged silica gel column with a gradient of 0 to 10% 2M ammonia-methanol in DCM

Sources & evidence

ORD record
ord-d5a1dc306b6d4246bbb0587cdc710b59
Source dataset
uspto-grants-2013_05
Patent number
US08450354B2

Reaction notes

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