Tris(hydroxymethyl)aminomethane → HCID 67188392, compound

HRID 1695202Notes

Reaction equation

HRID 1695202 reaction equation
Br[CH2:2][CH2:3][CH2:4][CH2:5][C:6](Cl)=[O:7].[S:9]1[CH:13]=[CH:12][CH:11]=[C:10]1[C:14]1[CH:15]=[C:16]([NH2:19])[NH:17][N:18]=1.CCN(C(C)C)C(C)C.C(O)C(N)(CO)CO.[C:37]([N:40]1[CH2:46][CH2:45][CH2:44][NH:43][CH2:42][CH2:41]1)(=[O:39])[CH3:38]>CC(N(C)C)=O>[S:9]1[CH:13]=[CH:12][CH:11]=[C:10]1[C:14]1[NH:18][N:17]=[C:16]([NH:19][C:6](=[O:7])[CH2:5][CH2:4][CH2:3][CH2:2][N:43]2[CH2:44][CH2:45][CH2:46][N:40]([C:37](=[O:39])[CH3:38])[CH2:41][CH2:42]2)[CH:15]=1

Participants

7

Reactant 5

HCID 6503Tris(hydroxymethyl)aminomethaneHCID 81531DiisopropylethylamineHCID 5211735-Bromovaleryl chlorideHCID 4186202N-AcetylhomopiperazineHCID 178507300HCID 178507300, compound

Product 1

HCID 67188392HCID 67188392, compoundYield 17%

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent

Conditions

Temperature
0 °C

Procedure

Bromovaleryl chloride (1.62 mL, 12.12 mmol) was dissolved in DMA (50 mL). To this, a solution of 5-thiophen-2-yl-2H-pyrazol-3-ylamine (2 g, 12.12 mmol) and DIEA (2.1 mL, 12.12 mmol) was added portionwise at 0° C. The reaction mixture was left stirring 1 hour at 0° C. and then for 2 hours at room temperature. After a total of 3 hours, PS-Trisamine (1 g, ˜4 mmol/g) was added to the mixture and left stirring for 2 hours. Then, N-acetylhomopiperazine (4.3 g, 30.3 mmol) was added and the mixture was left stirring at room temperature for a further 60 hours. After DMA evaporation under reduced pressure, water was added (50 mL) and this was extracted with ethyl acetate (3×30 mL). The aqueous layer was basified with solid NaOH and extracted with ethyl acetate at pH=10 and then again at pH=11. All the organic phases were reunited, dried and evaporated. The residue was purified by silica chromatography eluting with a gradient of ethyl acetate/methanol 9:1 up to ethyl acetate/methanol 8:2, to give the title compound as yellowish oil (800 mg, 17%).

Workup

  1. waitThe reaction mixture was left
  2. waitfor 2 hours at room temperature
  3. waitleft
  4. stirringstirring for 2 hours
  5. waitthe mixture was left
  6. stirringstirring at room temperature for a further 60 hours
  7. customAfter DMA evaporation under reduced pressure, water
  8. additionwas added (50 mL)
  9. extractionthis was extracted with ethyl acetate (3×30 mL)
  10. extractionextracted with ethyl acetate at pH=10
  11. customdried
  12. customevaporated
  13. customThe residue was purified by silica chromatography
  14. washeluting with a gradient of ethyl acetate/methanol 9:1 up to ethyl acetate/methanol 8:2

Sources & evidence

ORD record
ord-6cc6c255c98d4790a678596ad6f4ac53
Source dataset
uspto-grants-2012_04
Patent number
US08163729B2

Reaction notes

Loading…