Iodine → 2-{4-[4-(3-pyrrolidin-1-ylpropoxy)phenyl]tetrahydro-2H-pyran-4-yl}-1,3,4-oxadiazole

HRID 273068Notes

Reaction equation

HRID 273068 reaction equation
C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.II.C(N(CC)CC)C.[CH:29]([NH:31][NH:32][C:33]([C:35]1([C:41]2[CH:46]=[CH:45][C:44]([O:47][CH2:48][CH2:49][CH2:50][N:51]3[CH2:55][CH2:54][CH2:53][CH2:52]3)=[CH:43][CH:42]=2)[CH2:40][CH2:39][O:38][CH2:37][CH2:36]1)=[O:34])=O>ClCCl>[N:51]1([CH2:50][CH2:49][CH2:48][O:47][C:44]2[CH:43]=[CH:42][C:41]([C:35]3([C:33]4[O:34][CH:29]=[N:31][N:32]=4)[CH2:40][CH2:39][O:38][CH2:37][CH2:36]3)=[CH:46][CH:45]=2)[CH2:55][CH2:54][CH2:53][CH2:52]1

Participants

6

Reactant 4

HCID 807IodineHCID 8471TriethylamineHCID 11776TriphenylphosphineHCID 68576159N'-formyl-4-[4-(3-pyrrolidin-1-ylpropoxy)phenyl]tetrahydro-2H-pyran-4-carbohydrazide

Product 1

HCID 598374412-{4-[4-(3-pyrrolidin-1-ylpropoxy)phenyl]tetrahydro-2H-pyran-4-yl}-1,3,4-oxadiazoleYield 20.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent3×

Procedure

Triphenylphosphine (0.203 g, 0.78 mmol), iodine (0.198 g, 0.78 mmol) and triethylamine (0.217 mL, 1.56 mmol) were dissolved in dichloromethane (5 mL). The mixture was stirred at room temperature for 10 minutes. N′-formyl-4-[4-(3-pyrrolidin-1-ylpropoxy)phenyl]tetrahydro-2H-pyran-4-carbohydrazide (0.145 g, 0.39 mmol) in dichloromethane (5 mL) was added. The mixture was stirred at room temperature for 18 hours. The reaction mixture was diluted with dichloromethane (100 mL) and washed with water (25 mL). The organic was dried over sodium sulphate, filtered and concentrated in vacuo to provide a yellow oil. This was purified using preparative HPLC on Fraction-Lynx® eluting with water:acetonitrile:trifluoroacetic acid (95:5:0.1) to provide the title compound (0.028 g, 20%) as a clear oil. 1H NMR (400 MHz, CDCl3) δ1.78-1.85 (m, 4H), 2.05 (m, 2H), 2.30 (m, 2H), 2.56-2.60 (m, 4H), 2.60-2.70 (m, 4H), 3.59 (m, 2H), 3.90-4.05 (m, 4H), 6.90 (d, 2H), 7.20 (d, 2H), 8.30 (s, 1H). HRMS ESI+ m/z 358.2117 [MH]+.

Workup

  1. stirringThe mixture was stirred at room temperature for 18 hours
  2. washwashed with water (25 mL)
  3. dry with materialThe organic was dried over sodium sulphate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customto provide a yellow oil
  7. customThis was purified
  8. washeluting with water:acetonitrile:trifluoroacetic acid (95:5:0.1)

Sources & evidence

ORD record
ord-4ecd098a205f4265befba7e8f9325c6a
Source dataset
uspto-grants-2008_11
Patent number
US07456164B2

Reaction notes

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