Methyl iodide → HCID 59300419, compound

HRID 603463Notes

Reaction equation

HRID 603463 reaction equation
[H-].[Na+].[O:3]1[C:7]2[CH:8]=[CH:9][C:10]([C:12]3[CH:17]=[CH:16][N:15]=[C:14]([NH:18][CH2:19][CH2:20][CH2:21][O:22][C:23]4[CH:24]=[C:25]5[C:29](=[CH:30][CH:31]=4)[C@H:28]([CH2:32][C:33]([O:35][CH2:36][CH3:37])=[O:34])[CH2:27][CH2:26]5)[N:13]=3)=[CH:11][C:6]=2[O:5][CH2:4]1.I[CH3:39].[Cl-].[NH4+]>CN(C=O)C>[O:3]1[C:7]2[CH:8]=[CH:9][C:10]([C:12]3[CH:17]=[CH:16][N:15]=[C:14]([N:18]([CH3:39])[CH2:19][CH2:20][CH2:21][O:22][C:23]4[CH:24]=[C:25]5[C:29](=[CH:30][CH:31]=4)[C@H:28]([CH2:32][C:33]([O:35][CH2:36][CH3:37])=[O:34])[CH2:27][CH2:26]5)[N:13]=3)=[CH:11][C:6]=2[O:5][CH2:4]1

Participants

6

Reactant 4

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 59300508HCID 59300508, compound

Product 1

HCID 59300419HCID 59300419, compoundYield 264.6%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a suspension of sodium hydride (8.4 mg of a 60% dispersion, 0.210 mmol) in DMF (4 mL) cooled in an ice-bath, was added ethyl [(1S)-5-(3-{[4-(1,3-benzodioxol-5-yl)-2-pyrimidinyl]amino}propoxy)-2,3-dihydro-1H-inden-1-yl]acetate (Example 291, 50 mg, 0.105 mmol). The mixture was stirred for 15 min after which iodomethane (61 mg, 0.421 mmol) was added dropwise. The mixture was then stirred at rt for 16 h. A solution of ammonium chloride (10% in water) was added to the reaction mixture after which the mixture was concentrated under reduced pressure and brought to basic pH using a saturated solution of NaHCO3. The mixture was extracted with EtOAc (2×). The combined organic layers were washed with water and brine, dried, filtered, and then concentrated under reduced pressure. The residue was purified by silica gel flash column chromatography (1:2 EtOAc/hexanes) to give the product (136 mg, 69%) as a yellow oil. 1H NMR (400 MHz, CDCl3): δ 1.33 (t, 3H), 1.70-1.79 (m, 1H), 2.15-2.20 (m, 2H), 2.33-2.51 (m, 2H), 2.70 (dd, 1H), 2.82-2.95 (m, 2H), 3.30 (s, 3H), 3.53-3.64 (m, 1H), 3.71 (q, 2H), 4.13 (t, 2H), 4.22 (q, 2H), 6.01 (s, 2H), 6.65 (d, 1H), 6.75 (s, 1H), 6.90 (d, 2H), 7.05 (d, 1H), 7.62 (d, 1H), 7.15 (s, 1H), 8.30 (d, 1H); LC-MS: RT=3.01 min, (M+H)+ 490.2.

Workup

  1. temperaturecooled in an ice-bath
  2. additionwas added dropwise
  3. concentrationwas concentrated under reduced pressure
  4. extractionThe mixture was extracted with EtOAc (2×)
  5. washThe combined organic layers were washed with water and brine
  6. customdried
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customThe residue was purified by silica gel flash column chromatography (1:2 EtOAc/hexanes)

Sources & evidence

ORD record
ord-e3532f4d91234bf8b19e24e7ebc78509
Source dataset
uspto-grants-2011_03
Patent number
US07906653B2

Reaction notes

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