Ethyl acetate hexane → Methyl 2-(4-cyano-3-methylphenyl)-3-cyclopentenyl-2,3,3a,4-tetrahydrochromeno[4,3-c]pyrazole-7-carboxylate

HRID 505742Notes

Reaction equation

HRID 505742 reaction equation
[C:1]1([CH:6]=[C:7]2[C:16](=O)[C:15]3[C:10](=[CH:11][C:12]([C:18]([O:20][CH3:21])=[O:19])=[CH:13][CH:14]=3)[O:9][CH2:8]2)[CH2:5][CH2:4][CH2:3][CH:2]=1.Cl.[NH:23]([C:25]1[CH:32]=[CH:31][C:28]([C:29]#[N:30])=[C:27]([CH3:33])[CH:26]=1)[NH2:24].C(OCC)(=O)C.CCCCCC>C(O)C>[C:29]([C:28]1[CH:31]=[CH:32][C:25]([N:23]2[CH:6]([C:1]3[CH2:5][CH2:4][CH2:3][CH:2]=3)[CH:7]3[CH2:8][O:9][C:10]4[CH:11]=[C:12]([C:18]([O:20][CH3:21])=[O:19])[CH:13]=[CH:14][C:15]=4[C:16]3=[N:24]2)=[CH:26][C:27]=1[CH3:33])#[N:30]

Participants

5

Reactant 3

HCID 21226206Ethyl acetate hexaneHCID 469150334-Hydrazinyl-2-methylbenzonitrile hydrochlorideHCID 66722625Methyl 3-(cyclopentenylmethylene)-4-oxochroman-7-carboxylate

Product 1

HCID 66723040Methyl 2-(4-cyano-3-methylphenyl)-3-cyclopentenyl-2,3,3a,4-tetrahydrochromeno[4,3-c]pyrazole-7-carboxylateYield 33%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent2×

Conditions

Temperature
80 °C

Procedure

To a suspension of methyl 3-(cyclopentenylmethylene)-4-oxochroman-7-carboxylate; Preparation 34 (260 mg, 0.92 mmol) in ethanol (7 mL) was added 4-hydrazinyl-2-methylbenzonitrile hydrochloride; Preparation 2 (218 mg, 1.2 mmol). The slurry was heated to 80° C. for eighteen hours. The solution was returned to ambient temperature and the resulting solid was collected by vacuum filtration and washed with cold ethanol. Chromatography (normal phase, ethyl acetate/hexane) provided largely the cis isomer of methyl 2-(4-cyano-3-methylphenyl)-3-cyclopentenyl-2,3,3a,4-tetrahydrochromeno[4,3-c]pyrazole-7-carboxylate (yellow solid, 125 mg, 33% yield). LC/MS on 4.6×50 mm C-18 column, tR=6.98 minutes (10 to 90% acetonitrile/water over 8 minutes at 2 mL/minute with detection 254 nm, at 50° C.); ES-MS m/z 414 (M+H). 1H NMR (400 MHz, DMSO-d6) δ ppm 1.63-1.83 (m, 2H), 2.05-2.11 (m, 2H), 2.14-2.20 (m, 2H), 2.39 (s, 3H), 3.83 (s, 3H), 3.88 (dd, J=13.02, 10.34 Hz, 1H), 3.98-4.03 (m, 1H), 4.67 (dd, J=10.20, 5.64 Hz, 1H), 5.45 (d, J=11.01 Hz, 1H), 5.60 (br. s., 1H), 6.86 (br. s., 1H), 7.11 (br. s., 1H), 7.44 (d, J=1.34 Hz, 1H), 7.53 (d, J=8.59 Hz, 1H), 7.58 (dd, J=8.06, 1.61 Hz, 1H), 7.93 (d, J=8.06 Hz, 1H).

Workup

  1. customwas returned to ambient temperature
  2. filtrationthe resulting solid was collected by vacuum filtration
  3. washwashed with cold ethanol

Sources & evidence

ORD record
ord-6bb34b2220c048d98bd27e1729166de4
Source dataset
uspto-grants-2010_08
Patent number
US07781428B2

Reaction notes

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