Sodium Iodide → HCID 86607901, compound

HRID 736802Notes

Reaction equation

HRID 736802 reaction equation
[C:1]([O:5][NH:6][C:7]([C@:9]1([CH3:38])[C@H:14]([NH:15][S:16]([C:19]2[CH:24]=[CH:23][C:22]([O:25][CH2:26][C:27]3[C:36]4[C:31](=[CH:32][CH:33]=[CH:34][CH:35]=4)[N:30]=[C:29]([CH3:37])[CH:28]=3)=[CH:21][CH:20]=2)(=[O:18])=[O:17])[CH2:13][CH2:12][NH:11][CH2:10]1)=[O:8])([CH3:4])([CH3:3])[CH3:2].[I-].[Na+].C(=O)([O-])[O-].[K+].[K+].[CH2:47](Cl)[C:48]#[CH:49]>C(O)C>[C:1]([O:5][NH:6][C:7]([C@:9]1([CH3:38])[C@H:14]([NH:15][S:16]([C:19]2[CH:20]=[CH:21][C:22]([O:25][CH2:26][C:27]3[C:36]4[C:31](=[CH:32][CH:33]=[CH:34][CH:35]=4)[N:30]=[C:29]([CH3:37])[CH:28]=3)=[CH:23][CH:24]=2)(=[O:18])=[O:17])[CH2:13][CH2:12][N:11]([CH2:49][C:48]#[CH:47])[CH2:10]1)=[O:8])([CH3:4])([CH3:3])[CH3:2]

Participants

6

Reactant 4

HCID 5238Sodium IodideHCID 11430Potassium CarbonateHCID 122213-Chloro-1-propyneHCID 86607899HCID 86607899, compound

Product 1

HCID 86607901HCID 86607901, compoundYield 60%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

To 364 mg (0.673 mmol) of (3S,4R)-N-tert-butoxy-3-methyl-4-(4-((2-methylquinolin-4-yl)methoxy)phenylsulfonamido)piperidine-3-carboxamide (Example 47, Step 8) was added ethanol (6 mL), catalytic sodium iodide, potassium carbonate (112 mg, 0.812 mmol), and propargyl chloride (52 μL) and the resulting mixture was heated to reflux overnight. The solvent was then concentrated and the residue was dissolved in ethyl acetate. The organics were washed with saturated aqueous Na2CO3 (3×), dried over Na2SO4, concentrated, and then purified via column chromatography on silica gel eluting with 50% ethyl acetate/hexanes to give (3S,4R)-N-tert-butoxy-3-methyl-4-(4-((2-methylquinolin-4-yl)methoxy)phenylsulfonamido)-1-(prop-2-ynyl)piperidine-3-carboxamide (235 mg, 0.406 mmol, 60%) as a colorless solid. 1H NMR (400 MHz, CHLOROFORM-D) δ ppm 0.92-0.96 (m, 3H) 1.23-1.30 (m, 11H) 1.60-1.71 (m, 1H) 1.89-1.97 (m, 1H) 2.05-2.12 (m, 1H) 2.27-2.36 (m, 2H) 2.74 (s, 3H) 2.84-2.91 (m, 1H) 3.00 (ddd, J=12.06, 7.52, 4.17 Hz, 1H) 3.14 (dd, J=10.74, 2.15 Hz, 1H) 3.16-3.20 (m, 1H) 3.34 (dd, J=16.67, 2.53 Hz, 1H) 5.54 (s, 2H) 6.16 (d, J=7.58 Hz, 1H) 7.07-7.12 (m, 2H) 7.41 (s, 1H) 7.52-7.57 (m, 1H) 7.71 (ddd, J=8.46, 6.95, 1.26 Hz, 1H) 7.81-7.86 (m, 2H) 7.90 (d, J=7.58 Hz, 1H) 8.08 (d, J=8.59 Hz, 1H) 10.71 (s, 1H).

Workup

  1. temperaturethe resulting mixture was heated
  2. temperatureto reflux overnight
  3. concentrationThe solvent was then concentrated
  4. dissolutionthe residue was dissolved in ethyl acetate
  5. washThe organics were washed with saturated aqueous Na2CO3 (3×)
  6. dry with materialdried over Na2SO4
  7. concentrationconcentrated
  8. custompurified via column chromatography on silica gel eluting with 50% ethyl acetate/hexanes

Sources & evidence

ORD record
ord-4a8171a2763c4a6d9cab5bb243beef4f
Source dataset
uspto-grants-2009_09
Patent number
US07595327B2

Reaction notes

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