3-Furanol, tetrahydro- → HCID 42610017, compound

HRID 474154Notes

Reaction equation

HRID 474154 reaction equation
[OH:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][C:9]([NH:11][C@@H:12]([C:14]2[CH:19]=[CH:18][C:17]([NH:20][CH2:21][C:22]([F:25])([F:24])[F:23])=[CH:16][N:15]=2)[CH3:13])=[O:10])=[CH:4][CH:3]=1.O[CH:27]1[CH2:31][CH2:30][O:29][CH2:28]1.N(C(OC(C)(C)C)=O)=NC(OC(C)(C)C)=O.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>C1COCC1>[O:29]1[CH2:30][CH2:31][CH:27]([O:1][C:2]2[CH:3]=[CH:4][C:5]([CH2:8][C:9]([NH:11][C@@H:12]([C:14]3[CH:19]=[CH:18][C:17]([NH:20][CH2:21][C:22]([F:25])([F:23])[F:24])=[CH:16][N:15]=3)[CH3:13])=[O:10])=[CH:6][CH:7]=2)[CH2:28]1

Participants

6

Reactant 4

HCID 99603-Furanol, tetrahydro-HCID 11776TriphenylphosphineHCID 97268Di-tert-butyl azodicarboxylateHCID 68498915HCID 68498915, compound

Product 1

HCID 42610017HCID 42610017, compoundYield 70%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of the starting 2-(4-hydroxyphenyl)-N-((1R)-1-{5-[(2,2,2-trifluoroethyl)amino]pyridin-2-yl}ethyl)acetamide (60 mg, 0.17 mmol) in 0.5 ml of dry THF was added the 3-Hydroxytetrahydrofuran (14.92 mg, 0.169 mmol), Di-tert-butyl azodicarboxylate (58.5 mg, 0.254 mmol) and triphenylphosphine (66.6 mg, 0.254 mmol). The mixture was stirred at room temperature for Overnight. The reaction mixture was washed with saturated sodium bicarbonate solution and brine. Organics were extracted with CH2Cl2, dried over Na2SO4, filtered and concentrated in vacuo. Purification by reverse phase chromatography gave 2-[4-(tetrahydrofuran-3-yloxy)phenyl]-N-((1R)-1-{5-[(2,2,2-trifluoroethyl)amino]pyridin-2-yl}ethyl)acetamide as a white solid (0.050 g, 70%). 1H NMR (CDCl3, 400 MHz) δ 8.212 (d, J=2.38 Hz, 1H); 7.189 (m, 4H); 6.830 (m, 2H); 6.624 (d, J=7.15 Hz, 1H); 5.103 (quintet, J=6.95 Hz, 1H); 4.924 (m, 1H); 4.379 (dd, J=8.06, 15.93 Hz, 2H); 3.999 (m, 3H); 3.905 (m, 1H); 3.519 (s, 2H); 2.187 (m, 2H); 1.387 (d, J=6.78 Hz, 3H); MS (ES): m/z 425.2 (M+H). FLIPR alpha1I IP=91 nM.

Workup

  1. washThe reaction mixture was washed with saturated sodium bicarbonate solution and brine
  2. extractionOrganics were extracted with CH2Cl2
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customPurification by reverse phase chromatography

Sources & evidence

ORD record
ord-4fd6c4d27ecb4bc0a55d0ae833ac29b1
Source dataset
uspto-grants-2014_01
Patent number
US08637513B2

Reaction notes

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