HCID 10314231, compound → HCID 15226941, compound

HRID 1033554Notes

Reaction equation

HRID 1033554 reaction equation
[C:1]([C:3]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[N:5]([C:12]2[C:17]3[CH:18]=[C:19]([C:22]#[N:23])[CH:20]=[CH:21][C:16]=3[O:15][C:14]([CH3:25])([CH3:24])[CH:13]=2)[CH:4]=1)#[N:2]>CO.C(OCC)(=O)C.[OH-].[Pd+2].[OH-]>[C:22]([C:19]1[CH:20]=[CH:21][C:16]2[O:15][C:14]([CH3:25])([CH3:24])[CH2:13][CH:12]([N:5]3[C:6]4[C:11](=[CH:10][CH:9]=[CH:8][CH:7]=4)[C:3]([C:1]#[N:2])=[CH:4]3)[C:17]=2[CH:18]=1)#[N:23]

Participants

4

Reactant 1

HCID 10314231HCID 10314231, compound

Product 1

HCID 15226941HCID 15226941, compound

Reagents, catalysts & solvents 2

HCID 9942167Palladium hydroxideCatalystHCID 21584119Ethylacetate methanolSolvent

Procedure

4-(3-Cyano-1H-indol-1-yl)-2,2-dimethyl-2H-1-benzopyran-6-carbonitrile (25 mg, prepared according to Example 1) in methanol/ethyl acetate (3:1) was treated with an equal weight of palladium hydroxide catalyst and shaken under an atmosphere of hydrogen at 55 psi over 2 days, recharging the catalyst midway, to provide a 53:30 mixture of the desired compound and the starting material along with minor amounts of by-products. Another 250 mg of starting material was treated in an identical manner. Purification of the desired product from the combined reaction mixtures was effected by preparative reverse phase chromatography on a C-18 column, eluting with 85% of 90:10 MeOH:H2O with 0.1% trifluoroacetic acid and 15% of 10:90 MeOH:H2O with 0.1% trifluoroacetic acid at a flow rate of 49 mL/min. and injections of 75 mg. Product-containing fractions were concentrated to remove methanol and extracted twice with ethyl acetate. The organic extracts were washed with saturated sodium bicarbonate, water and brine, dried over anhydrous magnesium sulfate and concentrated in vacuo to give a residue of 50 mg. Final hexane trituration (decanted) gave the title compound (45 mg), m.p. 175°-178° C.: 1H NMR (CDCl3) δ 7.80-7.88 (m, 1H), 7.48-7.65 (m, 2H), 7.25-7.40 (m, 2H), 7.10-7.30 (m, 1H), 6.95-7.05 (m, 2H); 13C NMR (CDCl3) δ 157.8, 134.0, 133.8, 133.7, 133.6, 132.2, 124.7, 123.1, 120.8, 120.7, 119.6, 118.6, 115.4, 111.0, 110.9, 104.3, 77.4, 51.0, 39.4, 29.7, 24.7.

Workup

  1. customto provide

Sources & evidence

ORD record
ord-0a333f3dd380468c8a2ced9087d12253
Source dataset
uspto-grants-1994_05
Patent number
US05310932

Reaction notes

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