Aluminium lithium hydride → HCID 57520845, compound

HRID 2369385Notes

Reaction equation

HRID 2369385 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([CH2:8][C:9]([N:11]([CH3:31])[CH:12]2[CH2:17][CH2:16][CH:15]([NH:18][C:19]3[C:30]4[C:29]5[CH2:28][CH2:27][CH2:26][C:25]=5[S:24][C:23]=4[N:22]=[CH:21][N:20]=3)[CH2:14][CH2:13]2)=O)[CH:5]=[CH:6][CH:7]=1.[H-].[H-].[H-].[H-].[Al+3].[Li+]>O1CCCC1>[Cl:1][C:2]1[CH:3]=[C:4]([CH2:8][CH2:9][N:11]([CH3:31])[CH:12]2[CH2:13][CH2:14][CH:15]([NH:18][C:19]3[C:30]4[C:29]5[CH2:28][CH2:27][CH2:26][C:25]=5[S:24][C:23]=4[N:22]=[CH:21][N:20]=3)[CH2:16][CH2:17]2)[CH:5]=[CH:6][CH:7]=1

Participants

4

Reactant 2

HCID 21226445Aluminium lithium hydrideHCID 57520748HCID 57520748, compound

Product 1

HCID 57520845HCID 57520845, compoundYield 6%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
2.5 °C

Procedure

A solution of Compound I-102 (364 mg, 0.80 mmol, 1.00 equiv) in tetrahydrofuran (30 mL) was added dropwise into a solution of lithium aluminium tetrahydride (152 mg, 4.01 mmol, 5.00 equiv) in tetrahydrofuran (20 mL) with stirring at 0-5° C. The resulting solution was stirred for 5 h at 80° C. in an oil bath. The reaction was then quenched by the addition of 5 mL of water. The solids were filtered off. The filtrate was extracted with 3×100 mL of dichloromethane and the organic layers combined and dried over anhydrous sodium sulfate and concentrated under vacuum. The residue was purified by preparative HPLC (2#-Waters 2767-2(HPLC-08)) under the following conditions: column: Xbridge Prep Phenyl, 5 um, 19*150 mm; mobile phase: Water (50 mM ammonium bicarbonate) and acetonitrile (10.0% acetonitrile up to 33.0% in 2 min, up to 53.0% in 8 min, up to 100.0% in 1 min, down to 10.0% in 1 min); detector, UV 220 nm, to yield 20.3 mg (6%) of Compound I-107 as an off-white solid. 1H NMR (400 MHz, CDCl3) δ 8.36 (1H, s), 7.26-7.07 (4H, m), 4.85-4.83 (1H, d), 4.12-4.02 (1H, m), 3.00-2.97 (4H, m), 2.76-2.70 (4H, m), 2.58-2.49 (3H, m), 2.37 (3H, s). 2.27-2.23 (2H, d), 1.94-1.89 (2H, d), 1.71-1.47 (2H, q), 1.29-1.25 (2H, q). MS: m/z 441 (M+H)+.

Workup

  1. stirringThe resulting solution was stirred for 5 h at 80° C. in an oil bath
  2. customThe reaction was then quenched by the addition of 5 mL of water
  3. filtrationThe solids were filtered off
  4. extractionThe filtrate was extracted with 3×100 mL of dichloromethane
  5. dry with materialdried over anhydrous sodium sulfate
  6. concentrationconcentrated under vacuum
  7. customThe residue was purified by preparative HPLC (2#-Waters 2767-2(HPLC-08)) under the following conditions
  8. waitup to 53.0% in 8 min
  9. waitup to 100.0% in 1 min
  10. waitdown to 10.0% in 1 min)

Sources & evidence

ORD record
ord-6af6279e6331446398a0693200482342
Source dataset
uspto-grants-2014_04
Patent number
US08703941B2

Reaction notes

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