Trifluoroacetic acid → HCID 67068319, compound

HRID 1854327Notes

Reaction equation

HRID 1854327 reaction equation
C(OC([N:8]([C:36]1[N:37]=[C:38]2[CH:44]=[CH:43][N:42]([S:45]([C:48]3[CH:54]=[CH:53][C:51]([CH3:52])=[CH:50][CH:49]=3)(=[O:47])=[O:46])[C:39]2=[N:40][CH:41]=1)[CH2:9][C:10]([CH:12]1[CH:17]([CH3:18])[CH2:16][CH2:15][N:14]([C:19]([O:21][CH2:22][CH:23]2[C:35]3[CH:34]=[CH:33][CH:32]=[CH:31][C:30]=3[C:29]3[C:24]2=[CH:25][CH:26]=[CH:27][CH:28]=3)=[O:20])[CH2:13]1)=[O:11])=O)(C)(C)C.C(O)(C(F)(F)F)=O>C(Cl)Cl>[CH3:18][CH:17]1[CH2:16][CH2:15][N:14]([C:19]([O:21][CH2:22][CH:23]2[C:35]3[CH:34]=[CH:33][CH:32]=[CH:31][C:30]=3[C:29]3[C:24]2=[CH:25][CH:26]=[CH:27][CH:28]=3)=[O:20])[CH2:13][CH:12]1[C:10](=[O:11])[CH2:9][NH:8][C:36]1[N:37]=[C:38]2[CH:44]=[CH:43][N:42]([S:45]([C:48]3[CH:49]=[CH:50][C:51]([CH3:52])=[CH:53][CH:54]=3)(=[O:47])=[O:46])[C:39]2=[N:40][CH:41]=1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 69013101HCID 69013101, compound

Product 1

HCID 67068319HCID 67068319, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of (9H-fluoren-9-yl)methyl 3-(2-(tert-butoxycarbonyl(5-tosyl-5H-pyrrolo[2,3-b]pyrazin-2-yl)amino)acetyl)-4-methylpiperidine-1-carboxylate (0.627 g, 0.836 mmol, prepared using W from Preparation #20, LL, Z from Example #8, Step A) in DCM (10 mL) was added TFA (1.50 mL, 19.5 mmol) and the resulting mixture was stirred at ambient temperature under nitrogen for about 1 h. The solution was concentrated and the residue was partitioned between saturated aqueous NaHCO3 (25 mL) and EtOAc (25 mL). The organic phase was washed with brine (20 mL), dried over anhydrous MgSO4, filtered, and concentrated to yield crude (9H-fluoren-9-yl)methyl 4-methyl-3-(2-(5-tosyl-5H-pyrrolo[2,3-b]pyrazin-2-ylamino)acetyl)-piperidine-1-carboxylate as an amorphous brown solid. The crude material was added to 1,4-dioxane (5 mL), Lawesson's reagent (0.203 g, 0.502 mmol) was added, and the resulting suspension was heated at about 80° C. for about 20 min. The solvent was removed under reduced pressure and the residue was purified by silica gel chromatography eluting with a gradient of 0 to 1.5% MeOH/DCM to give (9H-fluoren-9-yl)methyl 4-methyl-3-(3-tosyl-3H-imidazo[1,2-a]pyrrolo[2,3-e]pyrazin-8-yl)piperidine-1-carboxylate as an off-white solid (0.21 g, 40%): LC/MS (Table 2, Method a) Rt=2.68 min; MS m/z: 632 (M+H)+.

Workup

  1. concentrationThe solution was concentrated
  2. customthe residue was partitioned between saturated aqueous NaHCO3 (25 mL) and EtOAc (25 mL)
  3. washThe organic phase was washed with brine (20 mL)
  4. dry with materialdried over anhydrous MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-ef96516c3e7c48d8a24dfd35cfb0b62d
Source dataset
uspto-grants-2015_02
Patent number
US08962629B2

Reaction notes

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