2-Chloro-4-hydrazinylbenzonitrile hydrochloride → HCID 86621297, compound

HRID 505746Notes

Reaction equation

HRID 505746 reaction equation
[F:1][C:2]([F:27])([F:26])[S:3]([O:6][C:7]1[CH:16]=[C:15]2[C:10]([C:11](=O)[C:12](=[CH:17][C:18]3[CH:23]=[CH:22][C:21]([F:24])=[CH:20][CH:19]=3)[CH2:13][O:14]2)=[CH:9][CH:8]=1)(=[O:5])=[O:4].Cl.[Cl:29][C:30]1[CH:37]=[C:36]([NH:38][NH2:39])[CH:35]=[CH:34][C:31]=1[C:32]#[N:33]>C(O)C>[F:26][C:2]([F:1])([F:27])[S:3]([O:6][C:7]1[CH:8]=[CH:9][C:10]2[C:11]3=[N:39][N:38]([C:36]4[CH:35]=[CH:34][C:31]([C:32]#[N:33])=[C:30]([Cl:29])[CH:37]=4)[CH:17]([C:18]4[CH:19]=[CH:20][C:21]([F:24])=[CH:22][CH:23]=4)[CH:12]3[CH2:13][O:14][C:15]=2[CH:16]=1)(=[O:5])=[O:4]

Participants

4

Reactant 2

HCID 221118492-Chloro-4-hydrazinylbenzonitrile hydrochlorideHCID 72296467HCID 72296467, compound

Product 1

HCID 86621297HCID 86621297, compoundYield 28%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of 3-(4-fluorobenzylidene)-4-oxochroman-7-yl trifluoromethanesulfonate; Preparation 35 (200 mg, 0.50 mmol), 2-chloro-4-hydrazinylbenzonitrile hydrochloride (Preparation 1) (152 mg, 0.75 mmol), and ethanol (5 mL) was stirred under argon at 80° C. for three hours. The mixture was cooled to room temperature and concentrated. Water was added, the residue extracted three times with methylene chloride, washed with brine, dried over magnesium sulfate, filtered and condensed. The crude product was purified by normal phase flash column chromatography on a 20 g silica gel column (100% methylene chloride). Pure fractions were pooled and condensed to give the title compound (yellow solid, 75 mg, 0.14 mmol, 28% yield). The title compound was largely present as (±)-(3SR,3aSR)-2-(3-chloro-4-cyanophenyl)-3-(4-fluorophenyl)-2,3,3a,4-tetrahydrochromeno[4,3-c]pyrazol-7-yl trifluoromethanesulfonate. 1H NMR (400 MHz, DMSO-d6) δ ppm 3.25 (dd, J=12.89, 10.47 Hz, 1H), 4.22-4.35 (m, 1H), 4.42 (dd, J=10.34, 6.04 Hz, 1H), 6.00 (d, J=11.28 Hz, 1H), 6.77-7.51 (m, 8H), 7.68 (d, J=8.59 Hz, 1H), 8.10 (d, J=9.40 Hz, 1H). ES-MS m/z 553 (M+H).

Workup

  1. temperatureThe mixture was cooled to room temperature
  2. concentrationconcentrated
  3. additionWater was added
  4. extractionthe residue extracted three times with methylene chloride
  5. washwashed with brine
  6. dry with materialdried over magnesium sulfate
  7. filtrationfiltered
  8. customcondensed
  9. customThe crude product was purified by normal phase flash column chromatography on a 20 g silica gel column (100% methylene chloride)
  10. customcondensed

Sources & evidence

ORD record
ord-0c9bb3748b9e42978d586cdf54f147b9
Source dataset
uspto-grants-2010_08
Patent number
US07781428B2

Reaction notes

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