Dichloromethane → HCID 58010071, compound

HRID 1854447Notes

Reaction equation

HRID 1854447 reaction equation
[NH:1]([C:3]1[N:4]=[C:5]2[CH:11]=[CH:10][N:9]([S:12]([C:15]3[CH:21]=[CH:20][C:18]([CH3:19])=[CH:17][CH:16]=3)(=[O:14])=[O:13])[C:6]2=[N:7][CH:8]=1)[NH2:2].C(Cl)Cl.[C:25]([O:29][C:30]([NH:32][CH:33]1[CH2:37][CH:36]([C:38](O)=[O:39])[CH:35]([CH2:41][CH3:42])[CH2:34]1)=[O:31])([CH3:28])([CH3:27])[CH3:26].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>O>[C:25]([O:29][C:30](=[O:31])[NH:32][CH:33]1[CH2:37][CH:36]([C:38]([NH:2][NH:1][C:3]2[N:4]=[C:5]3[CH:11]=[CH:10][N:9]([S:12]([C:15]4[CH:21]=[CH:20][C:18]([CH3:19])=[CH:17][CH:16]=4)(=[O:13])=[O:14])[C:6]3=[N:7][CH:8]=2)=[O:39])[CH:35]([CH2:41][CH3:42])[CH2:34]1)([CH3:28])([CH3:27])[CH3:26]

Participants

6

Reactant 4

HCID 6344DichloromethaneHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 580098102-Hydrazinyl-5-tosyl-5H-pyrrolo[2,3-b]pyrazineHCID 58010220HCID 58010220, compound

Product 1

HCID 58010071HCID 58010071, compoundYield 69%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

A round-bottomed flask was charged with 2-hydrazinyl-5-tosyl-5H-pyrrolo[2,3-b]pyrazine (2.0 g, 6.6 mmol, Step J) and DCM (40 mL) to give a brown suspension. 4-(tert-Butoxycarbonylamino)-2-ethylcyclopentanecarboxylic acid (2.0 g, 7.8 mmol, Step G), HATU (2.51 g, 6.59 mmol), and TEA (4.59 mL, 33.0 mmol) were added to the suspension and the resulting mixture was stirred at ambient temperature for about 24 h with dissolution occurring after about 2 h. Water (20 mL) was added and the layers were partitioned. The organic layer was washed with additional water (2×15 mL), brine (2×25 mL), dried over anhydrous MgSO4, filtered, and solvent was removed under reduced pressure to give a brown residue. The crude material was purified by silica gel chromatography eluting with a gradient of 0-10% MeOH/DCM. The recovered impure material was re-purified by silica gel chromatography eluting with a gradient of 0-10% MeOH/DCM. The product-containing fractions from the two columns were combined and concentrated to give tert-butyl-3-ethyl-4-(2-(5-tosyl-5H-pyrrolo[2,3-b]pyrazin-2-yl)hydrazinecarbonyl)cyclopentylcarbamate (2.45, 69%) as a brown solid: LC/MS (Table 2, Method d) Rt=1.47 min; MS m/z: 543 (M+H)+.

Workup

  1. customto give a brown suspension
  2. waitoccurring after about 2 h
  3. customthe layers were partitioned
  4. washThe organic layer was washed with additional water (2×15 mL), brine (2×25 mL)
  5. dry with materialdried over anhydrous MgSO4
  6. filtrationfiltered
  7. customsolvent was removed under reduced pressure
  8. customto give a brown residue
  9. customThe crude material was purified by silica gel chromatography
  10. washeluting with a gradient of 0-10% MeOH/DCM
  11. customThe recovered impure material was re-purified by silica gel chromatography
  12. washeluting with a gradient of 0-10% MeOH/DCM
  13. concentrationconcentrated

Sources & evidence

ORD record
ord-b2663156099b427a8038b78cdfb0e221
Source dataset
uspto-grants-2015_02
Patent number
US08962629B2

Reaction notes

Loading…