Triethylamine → HCID 46215557, compound

HRID 410171Notes

Reaction equation

HRID 410171 reaction equation
[S:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[C:2]1[NH:10][C:11]1[CH:26]=[CH:25][C:14]([O:15][C:16]2[N:24]=[CH:23][CH:22]=[CH:21][C:17]=2[C:18](O)=[O:19])=[CH:13][CH:12]=1.[CH:27]1([CH2:30][NH2:31])[CH2:29][CH2:28]1.C(N(CC)CC)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C)C=O.O>[S:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[C:2]1[NH:10][C:11]1[CH:26]=[CH:25][C:14]([O:15][C:16]2[N:24]=[CH:23][CH:22]=[CH:21][C:17]=2[C:18]([NH:31][CH2:30][CH:27]2[CH2:29][CH2:28]2)=[O:19])=[CH:13][CH:12]=1

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 75646CyclopropanemethanamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 462155562-(4-(Benzo[d]thiazol-2-ylamino)phenoxy)nicotinic acid

Product 1

HCID 46215557HCID 46215557, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a 100 mL round bottomed flask was added 2-(4-(benzo[d]thiazol-2-ylamino)phenoxy)nicotinic acid (0.3031 g, 0.834 mmol), cyclopropylmethanamine (0.0869 g, 1.22 mmol), and triethylamine (0.347 mL, 2.50 mmol) in N,N-dimethylformamide (3 mL) to stir for 5 min. HATU (0.3955 g, 0.917 mmol) was then added and allowed to stir overnight. The reaction mixture was diluted with water (10 mL) and extracted with DCM (3×10 mL). The organic extract was washed with water (1×10 mL), saturated sodium chloride (1×10 mL), saturated sodium bicarbonate (1×10 mL), dried with magnesium sulfate, filtered, and concentrated. The crude product was purified by reverse-phase preparative HPLC using a Phenomenex Gemini™ column, 5 micron, 150×30 mm, 0.1% trifluoroacetic acid in acetonitrile/water, gradient 10% to 100% over 15 min. The product was taken up in DCM and extracted with saturated sodium bicarbonate to remove TFA salts to provide 2-(4-(benzo[d]thiazol-2-ylamino)phenoxy)-N-(cyclopropylmethyl)nicotinamide as a white powder. MS (ESI, pos. ion) m/z: 417 (M+1). IC50 (uM) +++.

Workup

  1. stirringto stir overnight
  2. extractionextracted with DCM (3×10 mL)
  3. extractionThe organic extract
  4. washwas washed with water (1×10 mL), saturated sodium chloride (1×10 mL), saturated sodium bicarbonate (1×10 mL)
  5. dry with materialdried with magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe crude product was purified by reverse-phase preparative HPLC
  9. customover 15 min
  10. extractionextracted with saturated sodium bicarbonate
  11. customto remove TFA salts

Sources & evidence

ORD record
ord-86e9ad33f6294e9d8b02d45fb355c40f
Source dataset
uspto-grants-2014_06
Patent number
US08759532B2

Reaction notes

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