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 509531ノート

反応式

HRID 509531 の反応式
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]

参加物

6

反応物 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

生成物 1

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

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒

実験手順

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.

後処理

  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

出典と根拠

ORDレコード
ord-3b6b512b6bef4a34a4b4a1199f0e1dfd
出典データセット
uspto-grants-2015_08
特許番号
US09096584B2

反応ノート

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