Tetrahydrofuran → HCID 118062783, compound

HRID 920761Notes

Reaction equation

HRID 920761 reaction equation
[F:1][CH:2]([F:10])[CH:3]1[CH2:6][CH:5](C(O)=O)[CH2:4]1.C1C=CC(P([N:25]=[N+]=[N-])(C2C=CC=CC=2)=O)=CC=1.[Cl:28][C:29]1[CH:30]=[C:31]([C:36]2[C:44]([C:45]([NH2:47])=[O:46])=[C:39]3[CH2:40][NH:41][CH2:42][CH2:43][N:38]3[N:37]=2)[CH:32]=[CH:33][C:34]=1[F:35].C1[CH2:52][O:51]CC1>C1(C)C=CC=CC=1>[Cl:28][C:29]1[CH:30]=[C:31]([C:36]2[C:44]([C:45]([NH2:47])=[O:46])=[C:39]3[CH2:40][N:41]([C:52]([NH:25][CH:5]4[CH2:4][CH:3]([CH:2]([F:1])[F:10])[CH2:6]4)=[O:51])[CH2:42][CH2:43][N:38]3[N:37]=2)[CH:32]=[CH:33][C:34]=1[F:35]

Participants

6

Reactant 4

HCID 8028TetrahydrofuranHCID 199401P,P-Diphenylphosphinic azideHCID 847164043-(difluoromethyl)cyclobutane-1-carboxylic acidHCID 1180616272-(3-Chloro-4-fluorophenyl)-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazine-3-carboxamide

Product 1

HCID 118062783HCID 118062783, compound

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

A solution of Intermediate 252B (54.3 mg, 0.361 mmol), TEA (0.076 mL, 0.542 mmol) and DPPA (0.078 mL, 0.361 mmol) in toluene (5 mL) was stirred at 90° C. for 1.5 h. The reaction mixture was cooled to RT and in to it was added a solution of Intermediate 185B (50 mg, 0.181 mmol) in THF and stirred at RT for 4 h. The reaction mixture was quenched with water and extracted with ethyl acetate (3×5 mL). The combined organic layer was washed with a 10% aqueous solution of NaHCO3, water, and then dried over Na2SO4, filtered and the filtrate concentrated. The crude product was purified by preparative TLC. The crude material was loaded on a 0.5 mm silica gel plate and developed using 6% MeOH in CHCl3. Band containing desired product was removed and extracted into 10% MeOH in DCM, filtered and concentrated to offered Compounds 252 and 253 as off-white solid (mixture of cis and trans isomers). Both isomers were separated by chiral SFC.

Workup

  1. customThe reaction mixture was quenched with water
  2. extractionextracted with ethyl acetate (3×5 mL)
  3. washThe combined organic layer was washed with a 10% aqueous solution of NaHCO3, water
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationthe filtrate concentrated
  7. customThe crude product was purified by preparative TLC
  8. additionBand containing desired product
  9. customwas removed
  10. extractionextracted into 10% MeOH in DCM
  11. filtrationfiltered
  12. concentrationconcentrated
  13. customBoth isomers were separated by chiral SFC

Sources & evidence

ORD record
ord-b67177f6be2247bba50071c656bebd89
Source dataset
uspto-grants-2016_03
Patent number
US09273058B2

Reaction notes

Loading…