Methyl iodide → HCID 66609653, compound

HRID 1529581Notes

Reaction equation

HRID 1529581 reaction equation
[CH3:1]I.[H-].[Na+].[NH:5]1[C:13]2[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=2)[CH:7]=[C:6]1[C:14]([N:16]1[CH2:21][CH2:20][C:19]2[N:22]=[C:23]([CH2:25][O:26][C:27]3[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=3)[O:24][C:18]=2[CH2:17]1)=[O:15]>CN(C=O)C>[CH3:1][N:5]1[C:13]2[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=2)[CH:7]=[C:6]1[C:14]([N:16]1[CH2:21][CH2:20][C:19]2[N:22]=[C:23]([CH2:25][O:26][C:27]3[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=3)[O:24][C:18]=2[CH2:17]1)=[O:15]

Participants

5

Reactant 3

HCID 6328Methyl iodide2×HCID 24758Sodium hydride2×HCID 66613256HCID 66613256, compound

Product 1

HCID 66609653HCID 66609653, compoundYield 55.7%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

Methyl iodide (0.01 mL, 0.161 mmol) was added to a suspension of a 60% dispersion of sodium hydride in mineral oils (3.85 mg, 0.096 mmol) and 5-(1H-Indol-2-ylcarbonyl)-2-(phenoxymethyl)-4,5,6,7-tetrahydro[1,3]oxazolo[5,4-c]pyridine (0.03 g, 0.08 mmol) in DMF (2 mL). The mixture was stirred under microwave irradiation at 100° C. for 10 minutes. Then a 60% dispersion of sodium hydride in mineral oils (3.86 mg, 0.096 mmol) and methyl iodide (0.01 mL, 0.161 mmol) were added. The crude product was washed with a saturated solution of sodium hydrogen carbonate and extracted with diethyl ether. The organic layer was separated, dried (Na2SO4), filtered and the solvents evaporated in vacuo. The crude product was purified by RP HPLC on (C18 XBridge 19×100 5 um). Mobile phase (Gradient from 80% 0.1% NH4CO3H/NH4OH pH 9 solution in Water, 20% ACN to 0% 0.1% NH4CO3H/NH4OH pH 9 solution in Water, 100% ACN). The solvents were evaporated to yield 5-[(1-methyl-1H-indol-2-yl)carbonyl]-2-(phenoxymethyl)-4,5,6,7-tetrahydro[1,3]oxazolo[5,4-c]pyridine (17.25 mg, 55% yield) as a white solid. C23H21N3O3 1H NMR (500 MHz, CDCl3) δ ppm 2.82 (br. t, J=5.3 Hz, 2 H), 3.87 (s, 3 H), 4.05 (br. t, J=5.2 Hz, 2 H), 4.87 (s, 2 H), 5.14 (s, 2 H), 6.71 (s, 1 H), 6.98-7.07 (m, 3 H), 7.18 (t, J=7.4 Hz, 1 H), 7.29-7.37 (m, 3 H), 7.39 (d, J=8.4 Hz, 1 H), 7.66 (d, J=8.1 Hz, 1 H).

Workup

  1. washThe crude product was washed with a saturated solution of sodium hydrogen carbonate
  2. extractionextracted with diethyl ether
  3. customThe organic layer was separated
  4. dry with materialdried (Na2SO4)
  5. filtrationfiltered
  6. customthe solvents evaporated in vacuo
  7. customThe crude product was purified by RP HPLC on (C18 XBridge 19×100 5 um)
  8. customThe solvents were evaporated

Sources & evidence

ORD record
ord-7a21a9c9207e480485936e77f02fc115
Source dataset
uspto-grants-2015_07
Patent number
US09090632B2

Reaction notes

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