Triphenylphosphine → 3-{4-[2-(Morpholin-4-yl)ethoxy]phenyl}-1H-indazole-5-carbonitrile

HRID 1349706Notes

Reaction equation

HRID 1349706 reaction equation
[OH:1][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.O[CH2:45][CH2:46][N:47]1[CH2:52][CH2:51][O:50][CH2:49][CH2:48]1.N(C(OCC)=O)=NC(OCC)=O>CCOC(C)=O.CCOC(C)=O.CCCCCC.C1COCC1>[N:47]1([CH2:46][CH2:45][O:1][C:2]2[CH:7]=[CH:6][C:5]([C:8]3[C:16]4[C:11](=[CH:12][CH:13]=[C:14]([C:17]#[N:18])[CH:15]=4)[NH:10][N:9]=3)=[CH:4][CH:3]=2)[CH2:52][CH2:51][O:50][CH2:49][CH2:48]1

Participants

8

Reactant 4

HCID 11776TriphenylphosphineHCID 611632-MorpholinoethanolHCID 220568ethyl N-ethoxycarbonyliminocarbamateHCID 136379272HCID 136379272, compound

Product 1

HCID 224800663-{4-[2-(Morpholin-4-yl)ethoxy]phenyl}-1H-indazole-5-carbonitrileYield 71.1%

Reagents, catalysts & solvents 3

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolventHCID 21226206Ethyl acetate hexaneSolvent

Procedure

A mixture of 3-(4-hydroxyphenyl)-1-perhydro-2H-pyran-2-yl-1H-indazole-5-carbonitrile (400 mg, 1.25 mmol), triphenylphosphine (Ph3P, 1.31 g, 5.00 mmol, 4.00 equiv.), 4.00 mL THF, 4-(2-hydroxyethyl)morpholine (656 mg, 5.00 mmol, 4.00 equiv.), and diethyl azodicarboxylate (DEAD, 871 mg, 5.00 mmol, 4.00 equiv.) were stirred at room temperature for 5 days. The reaction was diluted with EtOAc and washed with 2×6.0 N aq. HCl. The combined aqueous layers were extracted with 2×EtOAc. The acidic aqueous layer was allowed to stand at room temperature for 5 h, and then added to enough 6.0 N aq. NaOH such that the final pH>12.0. The aqueous layer was extracted with EtOAc. The organic layer was dried (Na2SO4), filtered and concentrated. Purification by silica gel chromatography using 0–5% MeOH in EtOAc as eluent afforded an oil. Sonication of the oil in 15 mL of 10% EtOAc/hexane gave a precipitate. This mixture was diluted with 18 mL of hexanes, sonicated, and filtered affording the title compound (310 mg, 71.1% yield: ES-MS (m/z) 349 [M+1]+.

Workup

  1. washwashed with 2×6.0 N aq. HCl
  2. extractionThe combined aqueous layers were extracted with 2×EtOAc
  3. waitto stand at room temperature for 5 h
  4. additionadded to enough 6.0 N aq. NaOH such that the final pH>12.0
  5. extractionThe aqueous layer was extracted with EtOAc
  6. dry with materialThe organic layer was dried (Na2SO4)
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customPurification by silica gel chromatography
  10. customafforded an oil
  11. customgave a precipitate
  12. customsonicated
  13. filtrationfiltered

Sources & evidence

ORD record
ord-673b79c6ef5d40ffb1517194b1bd97cc
Source dataset
uspto-grants-2007_05
Patent number
US07211594B2

Reaction notes

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