Trifluoroacetic acid → 5-(1-ethylsulfonyl-3,6-dihydro-2H-pyridin-4-yl)-3-(5-phenyl-1,3,4-oxadiazol-2-yl)pyridin-2-amine

HRID 509531Notes

Reaction equation

HRID 509531 reaction equation
C(OC([NH:8][C:9]1[N:14]=[CH:13][C:12]([C:15]2[CH2:16][CH2:17][N:18](C(OC(C)(C)C)=O)[CH2:19][CH:20]=2)=[CH:11][C:10]=1[C:28]1[O:29][C:30]([C:33]2[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=2)=[N:31][N:32]=1)=O)(C)(C)C.C(O)(C(F)(F)F)=O.C(N(CC)CC)C.[CH2:53]([S:55](Cl)(=[O:57])=[O:56])[CH3:54]>C(Cl)Cl>[CH2:53]([S:55]([N:18]1[CH2:19][CH:20]=[C:15]([C:12]2[CH:11]=[C:10]([C:28]3[O:29][C:30]([C:33]4[CH:34]=[CH:35][CH:36]=[CH:37][CH:38]=4)=[N:31][N:32]=3)[C:9]([NH2:8])=[N:14][CH:13]=2)[CH2:16][CH2:17]1)(=[O:57])=[O:56])[CH3:54]

Participants

6

Reactant 4

HCID 6422Trifluoroacetic acidHCID 8471TriethylamineHCID 11667Ethanesulfonyl chlorideHCID 68104454tert-Butyl 4-(6-(tert-butoxycarbonylamino)-5-(5-phenyl-1,3,4-oxadiazol-2-yl)pyridin-3-yl)-5,6-dihydropyridine-1(2H)-carboxylate

Product 1

HCID 546733585-(1-ethylsulfonyl-3,6-dihydro-2H-pyridin-4-yl)-3-(5-phenyl-1,3,4-oxadiazol-2-yl)pyridin-2-amineYield 83.7%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

tert-Butyl 4-[6-(tert-butoxycarbonylamino)-5-(5-phenyl-1,3,4-oxadiazol-2-yl)-3-pyridyl]-3,6-dihydro-2H-pyridine-1-carboxylate (141.7 mg, 0.2727 mmol) was dissolved in DCM (2 mL) and treated with TFA (373.1 mg, 252.1 μL, 3.272 mmol) at ambient temperature. The reaction was allowed to stir at ambient temperature for 3 hours and then concentrated in vacuo. The resultant residue was redissolved in DCM and treated with triethylamine (55.19 mg, 76.02 μL, 0.5454 mmol) followed by ethanesulfonyl chloride (17.54 mg, 12.93 μL, 0.1364 mmol). The mixture was allowed to stir at ambient temperature for 16 hours and then concentrated in vacuo. The resultant residue was purified by reverse phase preparative HPLC [Waters Sunfire C18, 10 mM, 100 Å column, gradient 10%-95% B (solvent A: 0.05% TFA in water; solvent B: CH3CN) over 16 minutes at 25 mL/min]. The fractions were collected, passed through a sodium bicarbonate cartridge and freeze-dried to give the title compound as an off-white solid (47 mg, 42% Yield). 1H NMR (400.0 MHz, DMSO) δ 1.25 (t, 3H), 2.67 (br s, 2H), 3.16 (br s, 2H), 3.47 (br s, 2H), 3.94 (br s, 2H), 6.25 (br s, 1H), 7.44 (s, 2H), 7.64-7.69 (m, 3H), 8.22-8.24 (m, 2H), 8.29 (s, 1H) and 8.39 (s, 1H) ppm; MS (ES+) 411.95.

Workup

  1. concentrationconcentrated in vacuo
  2. dissolutionThe resultant residue was redissolved in DCM
  3. stirringto stir at ambient temperature for 16 hours
  4. concentrationconcentrated in vacuo
  5. customThe resultant residue was purified by reverse phase preparative HPLC [Waters Sunfire C18, 10 mM, 100 Å column, gradient 10%-95% B (solvent A: 0.05% TFA in water; solvent B: CH3CN) over 16 minutes at 25 mL/min]
  6. customThe fractions were collected
  7. customfreeze-dried

Sources & evidence

ORD record
ord-3b6b512b6bef4a34a4b4a1199f0e1dfd
Source dataset
uspto-grants-2015_08
Patent number
US09096584B2

Reaction notes

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