Tetrahydrofuran → HCID 118062838, compound

HRID 920806Notes

Reaction equation

HRID 920806 reaction equation
[F:1][C:2]1([F:12])[C:4]2([CH2:7][C:6]([CH3:11])(C(O)=O)[CH2:5]2)[CH2:3]1.C1C=CC(P([N:27]=[N+]=[N-])(C2C=CC=CC=2)=O)=CC=1.[Cl:30][C:31]1[CH:32]=[C:33]([C:38]2[C:46]([C:47]([NH2:49])=[O:48])=[C:41]3[CH2:42][NH:43][CH2:44][CH2:45][N:40]3[N:39]=2)[CH:34]=[CH:35][C:36]=1[F:37].C1[CH2:54][O:53]CC1>C1(C)C=CC=CC=1>[Cl:30][C:31]1[CH:32]=[C:33]([C:38]2[C:46]([C:47]([NH2:49])=[O:48])=[C:41]3[CH2:42][N:43]([C:54]([NH:27][C:6]4([CH3:11])[CH2:5][C:4]5([C:2]([F:1])([F:12])[CH2:3]5)[CH2:7]4)=[O:53])[CH2:44][CH2:45][N:40]3[N:39]=2)[CH:34]=[CH:35][C:36]=1[F:37]

Participants

6

Reactant 4

HCID 8028TetrahydrofuranHCID 199401P,P-Diphenylphosphinic azideHCID 1180616272-(3-Chloro-4-fluorophenyl)-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazine-3-carboxamideHCID 1180618232384666-57-1

Product 1

HCID 118062838HCID 118062838, compound

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
90 °C

Procedure

To a solution of Intermediate 326B (90 mg, 0.509 mmol), TEA (0.142 mL, 1.018 mmol) in toluene (10 mL) was added DPPA (0.110 mL, 0.509 mmol) and the reaction mixture was stirred at 90° C. for 2 h. The reaction mixture was cooled to RT and to it was added a solution of Intermediate 185B (100 mg, 0.339 mmol) in THF (3 mL) and stirred at RT for 4 h. The reaction mixture was quenched with water and the aq. layer was extracted with ethyl acetate (3×5 mL). The combined organic layers were washed with a 10% aq. solution of NaHCO3 and water, then dried over Na2SO4, filtered and concentrated. The crude reaction material was purified by preparative TLC and was loaded on a 0.5 mm silica gel plate. The plate was developed using 6% MeOH in CHCl3. The band containing the desired product was separated and extracted into 10% MeOH in DCM, and was then filtered and concentrated to afford cis and trans mixture of Compounds 326 and 327 as an off-white solid. The individual isomers were separated by preparative chiral SFC.

Workup

  1. temperatureThe reaction mixture was cooled to RT and to it
  2. stirringstirred at RT for 4 h
  3. customThe reaction mixture was quenched with water
  4. extractionthe aq. layer was extracted with ethyl acetate (3×5 mL)
  5. washThe combined organic layers were washed with a 10% aq. solution of NaHCO3 and water
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe crude reaction material
  10. customwas purified by preparative TLC
  11. additionThe band containing the desired product
  12. customwas separated
  13. extractionextracted into 10% MeOH in DCM
  14. filtrationwas then filtered
  15. concentrationconcentrated
  16. customto afford
  17. customThe individual isomers were separated by preparative chiral SFC

Sources & evidence

ORD record
ord-cd16bf5059ec425ba849a43544b7abcd
Source dataset
uspto-grants-2016_03
Patent number
US09273058B2

Reaction notes

Loading…