Sodium Hydroxide → 6-((4-((((trans)-2-Phenylcyclopropyl)amino)methyl)piperidin-1-yl)methyl)nicotinic acid

HRID 534203

반응식

HRID 534203 반응식
FC(F)(F)C([N:5]([C@@H:13]1[CH2:15][C@H:14]1[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)[CH2:6][CH:7]1[CH2:12][CH2:11][NH:10][CH2:9][CH2:8]1)=O.[CH:24]([C:26]1[CH:35]=[CH:34][C:29]([C:30]([O:32]C)=[O:31])=[CH:28][N:27]=1)=O.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].[OH-].[Na+]>ClCCCl.CO>[C:16]1([C@@H:14]2[CH2:15][C@H:13]2[NH:5][CH2:6][CH:7]2[CH2:8][CH2:9][N:10]([CH2:24][C:26]3[CH:35]=[CH:34][C:29]([C:30]([OH:32])=[O:31])=[CH:28][N:27]=3)[CH2:11][CH2:12]2)[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=1

참가 물질

7

반응물 4

HCID 14798Sodium HydroxideHCID 586269Methyl 6-formylpyridine-3-carboxylateHCID 5049666Sodium triacetoxyborohydrideHCID 867082342,2,2-trifluoro-N-((1R,2S)-2-phenylcyclopropyl)-N-(piperidin-4-ylmethyl)acetamide

생성물 1

HCID 665714876-((4-((((trans)-2-Phenylcyclopropyl)amino)methyl)piperidin-1-yl)methyl)nicotinic acid수율 75.6%

시약·촉매·용매 2

HCID 111,2-Dichloroethane용매HCID 887Methanol용매

실험 절차

To a solution 2,2,2-trifluoro-N-(trans-2-phenylcyclopropyl)-N-(piperidin-4-ylmethyl)acetamide (130 mg, 0.398 mmol) in 1,2-dichloroethane (DCE) (2 mL) were added methyl 6-formylnicotinate (86 mg, 0.518 mmol) and sodium triacetoxyborohydride (127 mg, 0.598 mmol), and the reaction mixture was stirred at room temperature for 18 h. The mixture was quenched with water (2 mL) and extracted with DCM (3×). The extract was dried (Na2SO4) and concentrated to give a crude product. The product was dissolved in methanol (2.000 mL) and sodium hydroxide (3M, 0.664 mL, 1.992 mmol) was added. The mixture was stirred at room temperature for 3 h and concentrated. The residue was treated with methanol and filtered. The filtrate was purified using reverse-phase HPLC under the acidic conditions to give 110 mg of product as pale yellow solid (HCl salt). MS: (M+H)+=366.4. 1H NMR (400 MHz, DMSO-d6) δ ppm 1.24 (m, 1H),1.54-1.73 (m, 3H), 1.98-2.12 (m, 3H), 2.59-2.72 (m, 1H), 2.94 (m, 4H), 3.45 (br. s., 2H), 4.54 (br. s., 2H), 7.16-7.25 (m, 3H), 7.27-7.35 (m, 2H), 7.81 (d, J=8.08 Hz, 1H), 8.38 (dd, J=8.08, 2.27 Hz, 1H), 9.12 (d, J=1.52 Hz, 1H), 9.78 (br. s., 2H), 10.72 (br. s., 1H).

후처리

  1. customThe mixture was quenched with water (2 mL)
  2. extractionextracted with DCM (3×)
  3. dry with materialThe extract was dried (Na2SO4)
  4. concentrationconcentrated
  5. customto give a crude product
  6. stirringThe mixture was stirred at room temperature for 3 h
  7. concentrationconcentrated
  8. additionThe residue was treated with methanol
  9. filtrationfiltered
  10. customThe filtrate was purified

출처 및 근거

ORD 기록
ord-aad4472a566045b4abfed8735feed37a
출처 데이터셋
uspto-grants-2014_10
특허 번호
US08853408B2

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