Pyridine → HCID 178480359, compound

HRID 1670647Notes

Reaction equation

HRID 1670647 reaction equation
[F:1][C:2]1[CH:3]=[CH:4][C:5]2=[C:6]([CH:36]=1)[O:7][CH2:8][C:9]1[C:34]([F:35])=[CH:33][CH:32]=[CH:31][C:10]=1/[C:11]/2=[CH:12]\[C:13]1[CH:18]=[CH:17][C:16]([NH:19][C@@H:20]2[CH2:25][CH2:24][N:23]([CH3:26])[CH2:22][C@H:21]2[OH:27])=[C:15]([N+:28]([O-])=O)[CH:14]=1.C(N(CC)CC)C.N1C=CC=CC=1.C1C=CC(O[C:57](OC2C=CC=CC=2)=[N:58][C:59]#[N:60])=CC=1>O1CCCC1.[Pt]>[F:1][C:2]1[CH:3]=[CH:4][C:5]2=[C:6]([CH:36]=1)[O:7][CH2:8][C:9]1[C:34]([F:35])=[CH:33][CH:32]=[CH:31][C:10]=1/[C:11]/2=[CH:12]\[C:13]1[CH:18]=[CH:17][C:16]2[N:19]([C@@H:20]3[CH2:25][CH2:24][N:23]([CH3:26])[CH2:22][C@H:21]3[OH:27])/[C:57](=[N:58]/[C:59]#[N:60])/[NH:28][C:15]=2[CH:14]=1

Participants

7

Reactant 4

HCID 1049PyridineHCID 8471TriethylamineHCID 688090Diphenyl N-CyanocarbonimidateHCID 57748788HCID 57748788, compound

Product 1

HCID 178480359HCID 178480359, compoundYield 26%

Reagents, catalysts & solvents 2

HCID 23939PlatinumCatalystHCID 8028TetrahydrofuranSolvent

Procedure

Dissolve (3R,4R)-4-[4-((E)-3,7-Difluoro-6H-dibenzo[b,e]oxepin-11-ylidenemethyl)-2-nitro-phenylamino]-1-methyl-piperidin-3-ol (0.009 mol, 4.48 g) in tetrahydrofuran (100 mL). Add triethylamine (0.018 mol, 1.83 g) and 10% platinum on carbon (2.2 g) and hydrogenate in a Parr shaker at 50 psi (H2) at room temperature for 4 h. Filter off the catalyst through a plug of diatomaceous earth. Add pyridine (100 mL) and diphenyl N-cyanocarbonimidate (0.009 mol, 2.16 g) to the filtrate. Stir at room temperature for 16 h and then heat at 60-70° C. for 8 h. Remove the solvent under reduced pressure. Dissolve the residue in dichloromethane and wash with water and saturated sodium bicarbonate solution. Dry the organic layer over anhydrous sodium sulfate, filter, and concentrate under reduced pressure. Purify on a silica gel column using 5% methanol in dichloromethane as eluent to obtain the title compound (1.2 g, 26%) as an off-white solid. 1H NMR (400 MHz, DMSO-d6) δ 1.66-1.8 (m, 1H), 1.75-1.78 (m, 1H), 1.87-1.90 (m, 1H), 2.03 (br s, 1H), 2.24 (s, 3H), 2.81 (br s, 1H), 2.96 (br s, 1H), 3.99 (br s, 1H), 4.31 (br s, 1H), 5.09 (s, 1H), 5.36 (br s, 1H), 5.46 (br s, 1H), 6.68 (dd, 1H), 6.82-6.87 (m, 3H), 6.99 (d, 1H), 7.09 (s, 1H), 7.26-7.35 (m, 3H), 7.62 (t, 1H), 12.49 (br s, 1H).

Workup

  1. filtrationFilter off the catalyst through a plug of diatomaceous earth
  2. temperatureheat at 60-70° C. for 8 h
  3. customRemove the solvent under reduced pressure
  4. dissolutionDissolve the residue in dichloromethane
  5. washwash with water and saturated sodium bicarbonate solution
  6. dry with materialDry the organic layer over anhydrous sodium sulfate
  7. filtrationfilter
  8. concentrationconcentrate under reduced pressure
  9. customPurify on a silica gel column

Sources & evidence

ORD record
ord-28ee2707c24c4a1081ea49d794047dc7
Source dataset
uspto-grants-2011_08
Patent number
US07994164B2

Reaction notes

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