Dimethylethylamine → HCID 54670317, compound

HRID 1186235Notes

Reaction equation

HRID 1186235 reaction equation
[CH:1]1([C:4](Cl)=O)[CH2:3][CH2:2]1.[F:7][C:8]1[CH:29]=[CH:28][C:11]([CH2:12][N:13]2[CH2:27][CH2:26][N:16]3[C:17]4[N:25]=[CH:24][CH:23]=[CH:22][C:18]=4[NH:19][CH2:20][CH2:21][CH:15]3[CH2:14]2)=[CH:10][CH:9]=1.CN(CC)C.[OH-].[Na+]>C(Cl)Cl.O.CO>[CH:1]1([CH2:4][N:19]2[CH2:20][CH2:21][CH:15]3[CH2:14][N:13]([CH2:12][C:11]4[CH:10]=[CH:9][C:8]([F:7])=[CH:29][CH:28]=4)[CH2:27][CH2:26][N:16]3[C:17]3[N:25]=[CH:24][CH:23]=[CH:22][C:18]2=3)[CH2:3][CH2:2]1

Participants

8

Reactant 4

HCID 11723DimethylethylamineHCID 14798Sodium HydroxideHCID 77637Cyclopropanecarbonyl chlorideHCID 67001538HCID 67001538, compound

Product 1

HCID 54670317HCID 54670317, compound

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

Cyclopropanecarbonyl chloride (0.043 ml, 0.478 mmol) was added to a solution of the product of Example 64C (97 mg, 0.31 mmol) in CH2Cl2 (2.0 mL). The mixture was stirred at room temperature for 2 hours and then concentrated under vacuum. The residue was taken up in 1 M NaOH (5 mL) and extracted with ethyl acetate (2×10 mL). The combined extract was washed with saturated brine (5 mL), dried (Na2SO4) and concentrated under vacuum. The residue was dissolved in tetrahydrofuran (5 mL) and stirred with alane-N,N-dimethylethylamine complex (Aldrich, 0.5 M in toluene, 2.9 mL, 1.45 mmol) at room temperature for 90 minutes. Methanol (1 mL) was added followed by water (5 mL) and 25% NaOH (1 mL). The mixture was stirred at room temperature for 10 minutes, and the aqueous phase was separated and extracted with ethyl acetate (2×7 mL). The combined organic was washed with saturated brine (5 mL), dried (Na2SO4) and concentrated under vacuum. The residue was purified by chromatography (SiO2 eluted with CH2Cl2—CH3OH 95:5) and then by HPLC (30×100 mm, C18, Waters XBridge™ column eluted with aqueous 0.1 M (NH4)2CO3—CH3OH, 80:20-0:100 over 15 minutes) to provide the title compound: 1H NMR (300 MHz, CDCl3) δ ppm 0.15-0.23 (m, 2H), 0.51-0.61 (m, 2H), 0.94-1.06 (m, 1H), 1.66-1.80 (m, 1H), 1.80-1.95 (m, 1H), 2.19 (t, J=9.7 Hz, 1H), 2.42 (td, J=10.5, 3.1 Hz, 1H), 2.59 (d, J=10.9 Hz, 1H), 2.74-2.84 (m, 1H), 2.95 (d, J=6.4 Hz, 2H), 3.22 (ddd, J=11.5, 6.1, 4.1 Hz, 1H), 3.30-3.39 (m, 1H), 3.38-3.48 (m, 2H), 3.52 (d, J=6.4 Hz, 2H), 3.61 (dt, J=12.5, 3.4 Hz, 1H), 6.75 (dd, J=7.8, 4.7 Hz, 1H), 6.95 (dd, J=7.8, 1.7 Hz, 1H), 6.97-7.05 (m, 2H), 7.32 (dd, J=8.5, 5.8 Hz, 2H), 7.80 (dd, J=4.7, 1.7 Hz, 1H); MS (DCI) m/z 367 (M+H)+.

Workup

  1. concentrationconcentrated under vacuum
  2. extractionextracted with ethyl acetate (2×10 mL)
  3. extractionThe combined extract
  4. washwas washed with saturated brine (5 mL)
  5. dry with materialdried (Na2SO4)
  6. concentrationconcentrated under vacuum
  7. dissolutionThe residue was dissolved in tetrahydrofuran (5 mL)
  8. stirringThe mixture was stirred at room temperature for 10 minutes
  9. customthe aqueous phase was separated
  10. extractionextracted with ethyl acetate (2×7 mL)
  11. washThe combined organic was washed with saturated brine (5 mL)
  12. dry with materialdried (Na2SO4)
  13. concentrationconcentrated under vacuum
  14. customThe residue was purified by chromatography (SiO2 eluted with CH2Cl2—CH3OH 95:5)
  15. washby HPLC (30×100 mm, C18, Waters XBridge™ column eluted with aqueous 0.1 M (NH4)2CO3—CH3OH, 80:20-0:100 over 15 minutes)

Sources & evidence

ORD record
ord-6a0b1ce2ac51405db7837376f1d64b58
Source dataset
uspto-grants-2014_03
Patent number
US08673896B2

Reaction notes

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