Dimethylethylamine → HCID 67002041, compound

HRID 1186239Notes

Reaction equation

HRID 1186239 reaction equation
CN(C)CC.[F:6][C:7]1[CH:41]=[CH:40][C:10]([CH2:11][N:12]2[CH2:39][CH2:38][N:15]3[C:16]4[N:37]=[CH:36][CH:35]=[CH:34][C:17]=4[N:18]([C:21]([C@@H:23]4[CH2:26][CH2:25][N:24]4[C:27]([O:29][C:30]([CH3:33])([CH3:32])[CH3:31])=[O:28])=O)[CH2:19][CH2:20][CH:14]3[CH2:13]2)=[CH:9][CH:8]=1>O1CCCC1>[F:6][C:7]1[CH:8]=[CH:9][C:10]([CH2:11][N:12]2[CH2:39][CH2:38][N:15]3[C:16]4[N:37]=[CH:36][CH:35]=[CH:34][C:17]=4[N:18]([CH2:21][C@@H:23]4[CH2:26][CH2:25][N:24]4[C:27]([O:29][C:30]([CH3:33])([CH3:32])[CH3:31])=[O:28])[CH2:19][CH2:20][CH:14]3[CH2:13]2)=[CH:40][CH:41]=1

Participants

4

Reactant 2

HCID 11723DimethylethylamineHCID 67001410HCID 67001410, compound

Product 1

HCID 67002041HCID 67002041, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of alane-dimethylethylamine complex (0.5 M in toluene, 3.1 mL, 1.55 mmol) was added to a solution of the product of example 68A (154 mg, 0.31 mmol) in tetrahydrofuran (5.0 mL) at room temperature under nitrogen. The turbid solution was stirred at room temperature for 3 hours and then quenched by addition of methanol (1 mL), followed after 5 minutes by water (5 mL) and 25% NaOH (0.5 mL). The aqueous layer was separated and extracted with ethyl acetate (2×5 mL), and the combined organic phases were washed with brine (5 mL), dried (Na2SO4) and concentrated under vacuum to provide residue which was purified by preparative HPLC on a Phenomenex® Luna® C8(2) 5 μm 100 Å AXIA column (30×75 mm) eluted with methanol:10 mM (NH4)2CO3 in water (50:50-95:5) to provide the title compound: 1H NMR (300 MHz, CDCl3) δ ppm 1.45 (s, 9H), 1.70-1.92 (m, 2H), 1.91-2.08 (m, 1H), 2.11-2.27 (m, 2H), 2.32-2.44 (m, 1H), 2.52-2.62 (m, 1H), 2.68-2.83 (m, 1H), 3.03-3.18 (m, 1H), 3.23-3.70 (m, 8H), 3.71-3.89 (m, 2H), 4.27-4.45 (m, 1H), 6.69-6.77 (m, 1H), 6.97-7.04 (m, 2H), 7.04-7.10 (m, 1H), 7.31 (dd, J=8.3, 5.6 Hz, 2H), 7.81 (dd, J=4.7, 1.4 Hz, 1H); MS (DCI) m/z 482 (M+H)+.

Workup

  1. customquenched by addition of methanol (1 mL)
  2. waitfollowed after 5 minutes by water (5 mL) and 25% NaOH (0.5 mL)
  3. customThe aqueous layer was separated
  4. extractionextracted with ethyl acetate (2×5 mL)
  5. washthe combined organic phases were washed with brine (5 mL)
  6. dry with materialdried (Na2SO4)
  7. concentrationconcentrated under vacuum
  8. customto provide residue which
  9. customwas purified by preparative HPLC on a Phenomenex® Luna® C8(2) 5 μm 100 Å AXIA column (30×75 mm)
  10. washeluted with methanol

Sources & evidence

ORD record
ord-82bfa2e452a44be99dde780ccafd74f7
Source dataset
uspto-grants-2014_03
Patent number
US08673896B2

Reaction notes

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