Triphenylphosphine → HCID 67546639, compound

HRID 2089522Notes

Reaction equation

HRID 2089522 reaction equation
O[CH:2]1[C:11]2[C:6](=[CH:7][C:8]([C:12]#[N:13])=[CH:9][CH:10]=2)[CH2:5][S:4][CH2:3]1.[N:14]1[CH:18]=[C:17]([C:19]([N:21]2[CH2:25][CH2:24][CH2:23][CH2:22]2)=[O:20])[NH:16][CH:15]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OC(C)C)=O)=NC(OC(C)C)=O>C1COCC1>[N:21]1([C:19]([C:17]2[N:16]([CH:2]3[C:11]4[C:6](=[CH:7][C:8]([C:12]#[N:13])=[CH:9][CH:10]=4)[CH2:5][S:4][CH2:3]3)[CH:15]=[N:14][CH:18]=2)=[O:20])[CH2:25][CH2:24][CH2:23][CH2:22]1

Participants

6

Reactant 4

HCID 11776TriphenylphosphineHCID 75555Diisopropyl diazene-1,2-dicarboxylateHCID 11321156HCID 11321156, compoundHCID 67546737HCID 67546737, compound

Product 1

HCID 67546639HCID 67546639, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of 4-hydroxy-isothiochroman-7-carbonitrile, which can be prepared as described in Example 12, (300 mg, 1.6 mmol) in THF (20 mL) is added (3H-imidazol-4-yl)-pyrrolidin-1-yl-methanone (200 mg, 1.2 mmol), and triphenylphosphine (420 mg, 1.6 mmol). The reaction is cooled to 0° C. and diisopropyl azodicarboxylate (310 μL, 1.6 mmol) is added. The reaction is permitted to warm to room temperature and stirred until LC-MS analysis indicates complete consumption of 4-hydroxy-isothiochroman-7-carbonitrile. The reaction mixture is diluted with saturated aqueous NaHCO3 and ethyl acetate. The layers are separated and the organic layer is dried with Na2SO4, filtered, and concentrated. The resulting residue is purified by silica gel flash chromatography (ethyl acetate-dichloromethane, 0:1 to 1:1) to afford 4-[5-(Pyrrolidine-1-carbonyl)-imidazol-1-yl]-isothiochroman-7-carbonitrile; MS: (ESI) m/z 339.2 (M+H)+; 1H NMR (400 MHz, CDCl3) δ ppm 1.88-2.08 (m, 4 H), 3.17-3.37 (m, 2 H), 3.53-3.68 (m, 2 H), 3.69-3.77 (m, 2 H), 3.79-3.98 (m, 2 H), 6.55 (t, J=4.6 Hz, 1 H), 7.19 (d, J=8.1 Hz, 1 H), 7.39 (s, 1 H), 7.43-7.48 (m, 2 H), 7.50 (s, 1 H). The HCl salt of the title compound can be prepared by dissolution in diethyl ether followed by treatment with an excess of 1N HCl in diethyl ether. The resulting heterogeneous solution is concentrated to furnish the HCl salt of 4-[5-(Pyrrolidine-1-carbonyl)-imidazol-1-yl]-isothiochroman-7-carbonitrile.

Workup

  1. temperatureto warm to room temperature
  2. customconsumption of 4-hydroxy-isothiochroman-7-carbonitrile
  3. additionThe reaction mixture is diluted with saturated aqueous NaHCO3 and ethyl acetate
  4. customThe layers are separated
  5. dry with materialthe organic layer is dried with Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe resulting residue is purified by silica gel flash chromatography (ethyl acetate-dichloromethane, 0:1 to 1:1)

Sources & evidence

ORD record
ord-a80773c81d694c6d9de93468f1ec704d
Source dataset
uspto-grants-2013_05
Patent number
US08436035B2

Reaction notes

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