Dimethylethylamine → HCID 67001934, compound

HRID 1186241Notes

Reaction equation

HRID 1186241 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]([CH:23]4[CH2:26][N:25]([C:27]([O:29][C:30]([CH3:33])([CH3:32])[CH3:31])=[O:28])[CH2:24]4)=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][CH:23]4[CH2:24][N:25]([C:27]([O:29][C:30]([CH3:33])([CH3:32])[CH3:31])=[O:28])[CH2:26]4)[CH2:19][CH2:20][CH:14]3[CH2:13]2)=[CH:40][CH:41]=1

Participants

4

Reactant 2

HCID 11723DimethylethylamineHCID 67001530HCID 67001530, compound

Product 1

HCID 67001934HCID 67001934, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Alane-dimethylethylamine complex (0.5 M in toluene, 3.1 mL, 1.55 mmol) was added to a solution of the product of Example 69A (154 mg, 0.31 mmol) in tetrahydrofuran (5.0 mL) at room temperature under nitrogen. The cloudy solution was stirred at room temperature for 2.5 hours and then quenched by addition of methanol (1 mL), followed after minutes by water (5 mL) and 25% NaOH (0.5 mL). The aqueous layer was separated and extracted with ethyl acetate (2×6 mL). The combined organic phases were washed with brine (5 mL), dried (Na2SO4) and concentrated under vacuum to provide a residue that was further 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 1.43 (s, 9H), 1.62-1.87 (m, 2H), 2.12 (t, J=10.0 Hz, 1H), 2.34 (td, J=10.7, 2.7 Hz, 1H), 2.59 (d, J=10.9 Hz, 1H), 2.72-2.86 (m, 2H), 2.89-3.00 (m, 1H), 3.14-3.26 (m, 1H), 3.28 (d, J=7.5 Hz, 2H), 3.31-3.43 (m, 2H), 3.44-3.56 (m, 2H), 3.56-3.63 (m, 2H), 3.69 (dt, J=12.8, 3.1 Hz, 1H), 3.96 (td, J=8.5, 3.7 Hz, 2H), 6.75 (dd, J=7.8, 4.7 Hz, 1H), 6.96 (dd, J=7.8, 1.4 Hz, 1H), 6.98-7.06 (m, 2H), 7.31 (dd, J=8.5, 5.4 Hz, 2H), 7.86 (dd, J=4.7, 1.7 Hz, 1H); MS (DCI) m/z 482 (M+H)+.

Workup

  1. customquenched by addition of methanol (1 mL)
  2. waitfollowed after minutes by water (5 mL) and 25% NaOH (0.5 mL)
  3. customThe aqueous layer was separated
  4. extractionextracted with ethyl acetate (2×6 mL)
  5. washThe combined organic phases were washed with brine (5 mL)
  6. dry with materialdried (Na2SO4)
  7. concentrationconcentrated under vacuum
  8. customto provide a residue that
  9. customwas further 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-d2ebbf5213634d0bb03ab5b77874c7ff
Source dataset
uspto-grants-2014_03
Patent number
US08673896B2

Reaction notes

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