2-(Dimethylamino)ethanol → HCID 22480245, compound

HRID 1349655Notes

Reaction equation

HRID 1349655 reaction equation
O[C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:16]3[C:11](=[CH:12][CH:13]=[C:14]([C:17]#[N:18])[CH:15]=3)[N:10](C3CCCCO3)[N:9]=2)=[CH:4][CH:3]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[CH3:44][N:45]([CH3:49])[CH2:46][CH2:47][OH:48].N(C(OCC)=O)=NC(OCC)=[O:53]>CCOC(C)=O>[CH3:44][N:45]([CH3:49])[CH2:46][CH2:47][O:48][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:16]3[C:11](=[CH:12][CH:13]=[C:14]([C:17]([NH2:18])=[O:53])[CH:15]=3)[NH:10][N:9]=2)=[CH:4][CH:3]=1

Participants

6

Reactant 4

HCID 79022-(Dimethylamino)ethanolHCID 11776TriphenylphosphineHCID 220568ethyl N-ethoxycarbonyliminocarbamateHCID 136379272HCID 136379272, compound

Product 1

HCID 22480245HCID 22480245, compoundYield 21.4%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent2×

Procedure

A mixture of 3-(4-hydroxyphenyl)-1-perhydro-2H-pyran-2-yl-1H-indazole-5-carbonitrile (400 mg, 1.25 mmol), triphenylphosphine (Ph3P, 656 mg, 2.50 mmol, 2.00 equiv.), 4.00 mL EtOAc, N,N-dimethylethanolamine (223 mg, 2.50 mmol, 2.00 equiv.), and diethyl azodicarboxylate (DEAD, 436 mg, 2.50 mmol, 2.00 equiv.) Was stirred at room temperature for 24 h. The mixture was diluted with EtOAc and washed with 6.0 N aq. HCl. The aqueous layer was extracted with 3×EtOAc and then added to enough 6.0 N aq. NaOH so that the final pH=14.0. This mixture was extracted with 3×EtOAc, and the combined organics were dried (Na2SO4), filtered, and concentrated. To the crude residue was added 6.00 mL of concentrated aq. HCl. The mixture was heated at 45° C. for 1.25 h. This mixture was then added to 25 mL of 6.0 N aq. NaOH that was stirred and cooled on a water bath. The mixture was extracted with 2×EtOAc, and the combined organics dried (Na2SO4). Purification by silica gel chromatography using 0.5% triethylamine (TEA) in CH2Cl2 containing 5–15% MeOH as eluent afforded the title compound (86.6 mg, 21.4% yield): 1H NMR (DMSO-d6) δ 13.34 (br s, 1H), 8.59 (s, 1H), 8.17 (br s, 1H), 8.00–7.85 (m, 3H), 7.58 (d, 2H), 7.35 (br s, 1H), 7.10 (d, 2H), 4.13 (t, 2H), 2.66 (t, 2H), 2.24 (s, 6H); ES-MS (m/z) 325 [M+1]+.

Workup

  1. washwashed with 6.0 N aq. HCl
  2. extractionThe aqueous layer was extracted with 3×EtOAc
  3. additionadded to enough 6.0 N aq. NaOH so that the final pH=14.0
  4. extractionThis mixture was extracted with 3×EtOAc
  5. dry with materialthe combined organics were dried (Na2SO4)
  6. filtrationfiltered
  7. concentrationconcentrated
  8. additionTo the crude residue was added 6.00 mL of concentrated aq. HCl
  9. temperatureThe mixture was heated at 45° C. for 1.25 h
  10. additionThis mixture was then added to 25 mL of 6.0 N aq. NaOH that
  11. stirringwas stirred
  12. temperaturecooled on a water bath
  13. extractionThe mixture was extracted with 2×EtOAc
  14. dry with materialthe combined organics dried (Na2SO4)
  15. customPurification by silica gel chromatography

Sources & evidence

ORD record
ord-54c93038b997473ab355c1ed7e20fef3
Source dataset
uspto-grants-2007_05
Patent number
US07211594B2

Reaction notes

Loading…