Toluene → HCID 118062866, compound

HRID 920759Notes

Reaction equation

HRID 920759 reaction equation
CC1CC([C:6]([OH:8])=O)C1.C1C=CC(P([N:23]=[N+]=[N-])(C2C=CC=CC=2)=O)=CC=1.[Cl:26][C:27]1[CH:28]=[C:29]([C:34]2[C:42]([C:43]([NH2:45])=[O:44])=[C:37]3[CH2:38][NH:39][CH2:40][CH2:41][N:36]3[N:35]=2)[CH:30]=[CH:31][C:32]=1[F:33].[C:46]1([CH3:52])[CH:51]=[CH:50][CH:49]=CC=1>C1COCC1>[Cl:26][C:27]1[CH:28]=[C:29]([C:34]2[C:42]([C:43]([NH2:45])=[O:44])=[C:37]3[CH2:38][N:39]([C:6]([NH:23][CH:46]4[CH2:51][CH:50]([CH3:49])[CH2:52]4)=[O:8])[CH2:40][CH2:41][N:36]3[N:35]=2)[CH:30]=[CH:31][C:32]=1[F:33]

Participants

6

Reactant 4

HCID 1140TolueneHCID 199401P,P-Diphenylphosphinic azideHCID 3044406Cyclobutanecarboxylic acid, 3-methyl-HCID 1180616272-(3-Chloro-4-fluorophenyl)-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazine-3-carboxamide

Product 1

HCID 118062866HCID 118062866, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of Intermediate 246A (77 mg, 0.679 mmol), TEA (0.142 mL, 1.018 mmol) and DPPA (0.146 mL, 0.679 mmol) in toluene (5 mL) 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 (1 mL) and stirred at RT for 4 h. The reaction mixture was quenched with water and the aqueous layer was extracted with ethyl acetate (3×5 mL) The combined organic layer was washed with an aqueous solution of 10% aq. NaHCO3, water, dried over Na2SO4, filtered and the filtrate concentrated to afford the crude product as an off-white solid. The crude material 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. The band containing the desired product was separated and extracted into 10% MeOH in DCM, filtered and the filtrate concentrated to afford a mixture cis and trans isomers as an off-white solid. The individual isomers were separated using preparative chiral SFC purification.

Workup

  1. customThe reaction mixture was quenched with water
  2. extractionthe aqueous layer was extracted with ethyl acetate (3×5 mL) The combined organic layer
  3. washwas washed with an aqueous solution of 10% aq. NaHCO3, water
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationthe filtrate concentrated

Sources & evidence

ORD record
ord-47b0caac386246ccb551c2359d30fe27
Source dataset
uspto-grants-2016_03
Patent number
US09273058B2

Reaction notes

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