Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [C:1]1([CH3:19])[CH:6]=[CH:5][C:4]([S:7]([O:10][CH:11]([CH3:18])[CH2:12][C:13]2[S:14][CH:15]=[CH:16][CH:17]=2)(=[O:9])=[O:8])=[CH:3][CH:2]=1.[C:20](Cl)(=[O:22])[CH3:21].[Cl-].[Cl-].[Cl-].[Al+3]>C(Cl)Cl>[C:20]([C:15]1[S:14][C:13]([CH2:12][CH:11]([O:10][S:7]([C:4]2[CH:3]=[CH:2][C:1]([CH3:19])=[CH:6][CH:5]=2)(=[O:9])=[O:8])[CH3:18])=[CH:17][CH:16]=1)(=[O:22])[CH3:21]
Reactant: Cc1ccc(S(=O)(=O)OC(C)Cc2cccs2)cc1
Reactant: CC(=O)Cl
Agent: [Al+3]
Agent: [Cl-]
Solvent: ClCCl
Product: CC(=O)c1ccc(CC(C)OS(=O)(=O)c2ccc(C)cc2)s1

Procedure:
2-(p-Toluenesulphonyloxy)-propylthiophene was reacted with acetyl chloride and aluminium trichloride in methylene chloride to give 5-acetyl-2-(p-toluenesulphonyloxy)-propylthiophene. With sodium azide in DMSO there was obtained therefrom 5-(3-azidopropyl)-2-thienyl methyl ketone. Oxidation with sodium hydrobromite gave 5-(3-azidopropyl)-2-thiophenecarboxylic acid, m.p. 71°-72°. Reaction of this acid with thionyl chloride and subsequent treatment with conc. ammonia yielded 5-(3-azidopropyl)-2-thiophenecarboxamide, m.p. 85°-87°. There was obtained therefrom after treatment with triphenylphosphine and hydrolysis 5-(3-aminopropyl)-2-thiophenecarboxamide, m.p. 143.5°-144° (from water).
Reaction SMILES: [N+](C1C=CC(O[C:11](=[O:36])[C@H:12]([CH2:21][CH2:22][CH2:23][CH2:24][NH:25][C:26]([O:28][CH2:29][C:30]2[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=2)=[O:27])[NH:13][C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])=CC=1)([O-])=O.Cl.[NH2:38][C@H:39]([C:41]([NH2:43])=[O:42])[CH3:40].C(N(CC)CC)C>CN(C)C=O>[C:14]([NH:13][C@H:12]([C:11]([NH:38][C@H:39]([C:41]([NH2:43])=[O:42])[CH3:40])=[O:36])[CH2:21][CH2:22][CH2:23][CH2:24][NH:25][C:26]([O:28][CH2:29][C:30]1[CH:31]=[CH:32][CH:33]=[CH:34][CH:35]=1)=[O:27])([O:16][C:17]([CH3:18])([CH3:19])[CH3:20])=[O:15]
Reactant: C[C@H](N)C(N)=O
Reactant: CC(C)(C)OC(=O)N[C@@H](CCCCNC(=O)OCc1ccccc1)C(=O)Oc1ccc([N+](=O)[O-])cc1
Agent: Cl
Solvent: CCN(CC)CC
Solvent: CN(C)C=O
Product: C[C@H](NC(=O)[C@H](CCCCNC(=O)OCc1ccccc1)NC(=O)OC(C)(C)C)C(N)=O
Yield: 95.4 %

Procedure:
Referring to Scheme 6, a solution of 5.0 g (0.010 mol) of Nα-BOC-Nε-CBZ-L-lysine p-nitrophenyl ester and 1.5 g (0.012 mol) of L-alanine amide hydrochloride and 1.67 ml (0.012 mol) of triethylamine in anhydrous N,N-dimethylformamide (50 ml) was stirred at room temperature for 16 hours before the solvent was removed in vacuo. The resulting residue was dissolved in ethyl acetate (200 ml) and washed with 3M NaOH (3×100 ml), water (3×100 ml), 1M HCl (2×100 ml) and finally with brine (100 ml). After drying over anhydrous sodium sulfate, the solution was filtered and concentrated in vacuo to give 4.3 g (96% yield) of Nα-BOC-Nε-CBZ-L-lysyl-L-alanine amide (6a) as a white solid. TLC: Rf 0.32 (chloroform-isopropanol 9:1); 1H NMR (d6 -DMSO) δ 1.20(d, 3H), 1.35(bm, 6H), 1.37(s, 9H), 2.97(m, 2H), 3.86(m, 1H), 4.21(m, 1H), 5.00(s, 2H), 6.95(d, 1H), 7.06(s, 1H), 7.24(t, 1H), 7.34(m, 6H), 7.78(d, 1H); 13C NMR (d6 -DMSO) δ 18.6, 22.8, 28.2, 29.2, 31.4, 40.1, 47.8, 54.5, 65.2, 78.2, 127.8, 128.4, 137.3, 155.5, 156.1, 171.7, 174.2.
Reaction SMILES: [OH:1]OS([O-])=O.[K+].[C:7]([C:11]1[N:15]([CH2:16][CH:17]2[CH2:22][CH2:21][O:20][CH2:19][CH2:18]2)[C:14]2[CH:23]=[CH:24][C:25]([S:27]([N:30]3[CH:34]=[C:33]([CH:35]=[O:36])[CH:32]=[N:31]3)(=[O:29])=[O:28])=[CH:26][C:13]=2[N:12]=1)([CH3:10])([CH3:9])[CH3:8]>CN(C=O)C>[C:7]([C:11]1[N:15]([CH2:16][CH:17]2[CH2:22][CH2:21][O:20][CH2:19][CH2:18]2)[C:14]2[CH:23]=[CH:24][C:25]([S:27]([N:30]3[CH:34]=[C:33]([C:35]([OH:1])=[O:36])[CH:32]=[N:31]3)(=[O:29])=[O:28])=[CH:26][C:13]=2[N:12]=1)([CH3:10])([CH3:8])[CH3:9]
Reactant: O=S([O-])OO
Reactant: CC(C)(C)c1nc2cc(S(=O)(=O)n3cc(C=O)cn3)ccc2n1CC1CCOCC1
Agent: [K+]
Solvent: CN(C)C=O
Product: CC(C)(C)c1nc2cc(S(=O)(=O)n3cc(C(=O)O)cn3)ccc2n1CC1CCOCC1
Temperature: 25 °C
Reaction time: 8 h
Yield: 84 %

Procedure:
Oxone (596 mg, 0.97 mmol) was added to a solution of 1-{[2-tert-butyl-1-(tetrahydro-2H-pyran-4-ylmethyl)-1H-benzimidazol-5-yl]sulfonyl}-1H-pyrazole-4-carbaldehyde (380 mg, 0.88 mmol) (see example 23 for preparation) in DMF (15 mL). The resulting mixture was stirred overnight at room temperature and the solvent was concentrated. The residue was dissolved in DCM, washed with 10% HCl solution and dried over anhydrous Na2SO4. The solvent was concentrated to provide the title compound as white solid Yield: 330 mg (74%); MS (ESI) (M+H)+=447.09.
Reaction SMILES: Cl.CN(C)CCCN=C=NCC.[C:13]1([C:19]2[CH:28]=[C:27]([C:29](O)=[O:30])[C:26]3[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=3)[N:20]=2)[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1.ON1C2C=CC=CC=2N=N1.[NH2:42][CH2:43][CH2:44][CH2:45][CH2:46][N:47]1[C:59]2[C:58]3[CH:57]=[CH:56][CH:55]=[CH:54][C:53]=3[N:52]=[C:51]([NH2:60])[C:50]=2[N:49]=[C:48]1[CH2:61][CH2:62][O:63][CH3:64]>ClCCl.N1C=CC=CC=1>[NH2:60][C:51]1[C:50]2[N:49]=[C:48]([CH2:61][CH2:62][O:63][CH3:64])[N:47]([CH2:46][CH2:45][CH2:44][CH2:43][NH:42][C:29]([C:27]3[C:26]4[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=4)[N:20]=[C:19]([C:13]4[CH:14]=[CH:15][CH:16]=[CH:17][CH:18]=4)[CH:28]=3)=[O:30])[C:59]=2[C:58]2[CH:57]=[CH:56][CH:55]=[CH:54][C:53]=2[N:52]=1
Reactant: COCCc1nc2c(N)nc3ccccc3c2n1CCCCN
Reactant: O=C(O)c1cc(-c2ccccc2)nc2ccccc12
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Agent: On1nnc2ccccc21
Solvent: c1ccncc1
Solvent: ClCCl
Product: COCCc1nc2c(N)nc3ccccc3c2n1CCCCNC(=O)c1cc(-c2ccccc2)nc2ccccc12
Temperature: 25 °C
Yield: 44.6 %

Procedure:
1-[3-(Dimethylamino)propyl]-3-ethylcarbodiimide hydrochloride (0.57 g, 3.0 mmol) was added dropwise to a chilled (0° C.) solution of 2-phenyl-4-quinolinecarboxylic acid (0.5 g, 3.7 mmol), 1-hydroxybenzotriazole (0.5 g, 3.7 mmol), pyridine (2.2 ml), and dichloromethane (20 ml). The reaction was maintained for 15 min followed by the dropwise addition of 1-(4-aminobutyl)-2-(2-methoxyethyl)-1H-imidazo[4,5-c]quinolin-4-amine (0.8 g, 2.55 mmol) in dichloromethane (100 ml). The reaction was maintained at room temperature overnight. The solvent was removed in vacuo and the residue was purified by flash column chromatography (silica gel, 9:1 dichloromethane\methanol). The fractions containing product were combined, washed with saturated aqueous sodium bicarbonate, dried (MgSO4), filtered, and concentrated to provide 0.62 g of N4-[4-(4-amino-2-(2-methoxyethyl)-1H-imidazo[4,5-c]quinolin-1-yl)butyl]-2-phenyl-4-quinolinecarboxamide as a yellow crystalline solid, m.p. 118° C. (decomposition). 1H NMR (300 MHz, DMSO-d6) δ 8.88 (t, J=5.7 Hz, 1H), 8.24-8.21 (m, 2H), 8.13-8.01(m, 4H), 7.83-7.78 (m, 1H), 7.62-7.48 (m, 5H), 7.36 (m, 1H), 7.20 (dt, J=7.6, 1.2 Hz, 1H), 6.54 (broad s, 2H), 4.62 (t, J=7.2 Hz, 2H), 3.83 (t, J=6.7 Hz, 2H), 3.45 (m, 2H), 3.29-3.20 (m, 5H), 1.96 (m, 2H), 1.79 (m, 2H); MS (EI) m/e 544.2589 (544.2587 calcd for C33H32N6O2).
Reaction SMILES: C([O:3][C:4]([C:6]1[N:7]=[C:8]([CH2:11][O:12][C:13]2[CH:18]=[CH:17][C:16](I)=[CH:15][CH:14]=2)[S:9][CH:10]=1)=[O:5])C.[CH2:20]1[O:28][C:27]2[CH:26]=[CH:25][C:24](B(O)O)=[CH:23][C:22]=2[O:21]1.C(=O)([O-])[O-].[K+].[K+]>O1CCOCC1.O>[O:21]1[C:22]2[CH:23]=[CH:24][C:25]([C:16]3[CH:15]=[CH:14][C:13]([O:12][CH2:11][C:8]4[S:9][CH:10]=[C:6]([C:4]([OH:3])=[O:5])[N:7]=4)=[CH:18][CH:17]=3)=[CH:26][C:27]=2[O:28][CH2:20]1
Reactant: CCOC(=O)c1csc(COc2ccc(I)cc2)n1
Reactant: OB(O)c1ccc2c(c1)OCO2
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: C1COCCO1
Product: O=C(O)c1csc(COc2ccc(-c3ccc4c(c3)OCO4)cc2)n1

Procedure:
A solution of 2-(4-iodo-phenoxymethyl)-thiazole-4-carboxylic acid ethyl ester (of intermediate 2; 75 mg, 0.2 mmol) in dioxane (4 mL) was added to a reaction tube containing 3,4-methylenedioxybenzeneboronic acid (ASDI Incorporated, Newark, Del.; 100 mg, 0.6 mmol). A solution of potassium carbonate (80 mg, 0.6 mmol) in water (0.4 mL) was added and the mixture was degassed. A solution of bis(tricyclohexylphosphine)-palladium (available from Strem Chemicals, Inc., Newburyport, Mass.; 7 mg, 0.01 mmol) in dioxane (0.5 mL) was added and the tube was heated in a microwave oven at 170 degrees for 25 min. The solution was acidified, filtered through silica gel, evaporated, and triturated with aqueous methanol to give 2-(4-benzo[1,3]dioxol-5-yl-phenoxymethyl)-thiazole-4-carboxylic acid. Mass spectrum MH+=356.
Reaction SMILES: [H-].C([Al+]CC(C)C)C(C)C.[CH:11]1([NH:17][C:18]2[CH:25]=[CH:24][C:21]([C:22]#N)=[CH:20][CH:19]=2)[CH2:16][CH2:15][CH:14]=[CH:13][CH2:12]1.C[OH:27]>C1(C)C=CC=CC=1>[CH:11]1([NH:17][C:18]2[CH:25]=[CH:24][C:21]([CH:22]=[O:27])=[CH:20][CH:19]=2)[CH2:16][CH2:15][CH:14]=[CH:13][CH2:12]1
Reactant: CO
Reactant: N#Cc1ccc(NC2CC=CCC2)cc1
Agent: CC(C)C[Al+]CC(C)C
Agent: [H-]
Solvent: Cc1ccccc1
Product: O=Cc1ccc(NC2CC=CCC2)cc1
Temperature: 0 °C

Procedure:
Di-isobutylaluminum hydride (54 ml., 25% solution in toluene) is added with stirring to a solution of 12.1 g. of 4-(cyclohex-3-enylamino)benzonitrile under a nitrogen atmosphere. After addition is completed, the solution stirred for one hour. A solution of methanol in toluene (50 ml., 1:1) is added over 30 minutes and the mixture is poured into 500 ml. vigorously stirred ice-cold 50% aqueous sulfuric acid. The mixture is filtered and the organic layer separated. The aqueous solution is extracted twice with toluene (100 ml.) and the combined organic layers are washed with acqueous sodium bicarbonate, dried over magnesium sulfate, decolorized with charcoal, filtered and evaporated in vacuo to give a light yellow crystalline solid. The product is recrystallized from dichloromethane/hexane giving colorless needles.
Reaction SMILES: P(N(C)C)(N(C)C)N(C)C.[C:11](Br)(Br)([F:13])[F:12].[CH3:16][O:17][C:18]1[CH:32]=[CH:31][C:21]([CH2:22][N:23]2[C:27](=[O:28])[CH2:26][CH:25]([CH:29]=O)[CH2:24]2)=[CH:20][CH:19]=1.[PH4+]>C1COCC1>[F:12][C:11]([F:13])=[CH:29][CH:25]1[CH2:24][N:23]([CH2:22][C:21]2[CH:31]=[CH:32][C:18]([O:17][CH3:16])=[CH:19][CH:20]=2)[C:27](=[O:28])[CH2:26]1
Reactant: FC(F)(Br)Br
Reactant: COc1ccc(CN2CC(C=O)CC2=O)cc1
Agent: CN(C)P(N(C)C)N(C)C
Agent: [PH4+]
Solvent: C1CCOC1
Product: COc1ccc(CN2CC(C=C(F)F)CC2=O)cc1
Temperature: 25 °C
Reaction time: 1 h
Yield: 57.3 %

Procedure:
In a three necked flask under argon, (Me2N)3P (11.53 ml, 0.063 mol) is added to a solution of CF2Br2 (6.6 g, 0.031 mol) in THF (30 ml) at −78° C. (appearance of a white precipitate) and warmed to room temperature. A solution of the 1-(4-methoxy-benzyl)-5-oxo-pyrrolidine-3-carbaldehyde a3 (3.7 g, 0.016 mol) in THF (30 ml) is added dropwise to the pre-formed phosphonium salt. After 1 h, the reaction mixture is filtered through celite and concentrated in vacuo. The reaction mixture is diluted with hexane, washed with brine, dried over MgSO4 and concentrated in vacuo to afford the crude olefin which is purified by column chromatography on silicagel (CH2Cl2/MeOH: 99/01 (v/v)) to afford 2.45 g of the difluorovinyl derivative a4 (58%).
Reaction SMILES: [F:1][CH:2]([F:13])[O:3][C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=1[N:10]=[C:11]=[O:12].[NH2:14][C:15]1[CH:20]=[N:19][CH:18]=[CH:17][N:16]=1>COC(OC)C>[F:1][CH:2]([F:13])[O:3][C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=1[NH:10][C:11]([NH:14][C:15]1[CH:20]=[N:19][CH:18]=[CH:17][N:16]=1)=[O:12]
Reactant: Nc1cnccn1
Reactant: O=C=Nc1ccccc1OC(F)F
Agent: COC(C)OC
Product: O=C(Nc1cnccn1)Nc1ccccc1OC(F)F
Temperature: 25 °C

Procedure:
2-(Difluoromethoxy)phenylisocyanate (1.0 g, 5.4 mmol) and aminopyrazine (0.51 g, 5.4 mmol) were reacted for 6 hours in refluxing dimethoxy-ethane (20 mL). The reaction mixture was cooled to room temperature to precipitate the product, which was collected by filtration, washed with ethyl acetate, and dried in vacuo (765 mg, 50%). 1H NMR (300 Mhz, d6-DMSO) δ: 10.49 (br s, 1H), 10.26 (s, 1H), 8.83 (s, 1 H), 8.35-8.24 (m, 3H), 7.53-7.00 (m,4H).
Reaction SMILES: [NH2:1][C:2]1[C:10]2[O:9][C:8]([CH3:12])([CH3:11])[C:7](=[O:13])[C:6]=2[C:5]([Cl:14])=[CH:4][CH:3]=1.Cl[C:16](OC(Cl)(Cl)Cl)=[O:17]>C1(C)C=CC=CC=1>[Cl:14][C:5]1[C:6]2[C:7](=[O:13])[C:8]([CH3:11])([CH3:12])[O:9][C:10]=2[C:2]([N:1]=[C:16]=[O:17])=[CH:3][CH:4]=1
Reactant: O=C(Cl)OC(Cl)(Cl)Cl
Reactant: CC1(C)Oc2c(N)ccc(Cl)c2C1=O
Solvent: Cc1ccccc1
Product: CC1(C)Oc2c(N=C=O)ccc(Cl)c2C1=O
Yield: 99.9 %

Procedure:
By the method of Example 1, Step F, 2.70 g (0.012 mole) of 7-amino-4-chloro-2,3-dihydro-2,2-dimethylbenzofuran-3-one was reacted with 2.37 g (0.012 mole) of trichloromethyl chloroformate in toluene, yielding 2.85 g of 4-chloro-2,3-dihydro-2,2-dimethylbenzofuran-3-on-7-yl isocyanate.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[C:6]([Cl:8])[CH:5]=[CH:4][C:3]=1[C:9]1[C:14]([N+:15]([O-:17])=[O:16])=[CH:13][CH:12]=[C:11](Cl)[N:10]=1.[NH2:19][CH2:20][CH2:21][NH:22][C:23]1[CH:28]=[CH:27][C:26]([N+:29]([O-:31])=[O:30])=[C:25]([NH2:32])[N:24]=1.C(N(CC)C(C)C)(C)C>CN(C=O)C>[NH2:32][C:25]1[N:24]=[C:23]([NH:22][CH2:21][CH2:20][NH:19][C:11]2[CH:12]=[CH:13][C:14]([N+:15]([O-:17])=[O:16])=[C:9]([C:3]3[CH:4]=[CH:5][C:6]([Cl:8])=[CH:7][C:2]=3[Cl:1])[N:10]=2)[CH:28]=[CH:27][C:26]=1[N+:29]([O-:31])=[O:30]
Reactant: O=[N+]([O-])c1ccc(Cl)nc1-c1ccc(Cl)cc1Cl
Reactant: NCCNc1ccc([N+](=O)[O-])c(N)n1
Solvent: CCN(C(C)C)C(C)C
Solvent: CN(C)C=O
Product: Nc1nc(NCCNc2ccc([N+](=O)[O-])c(-c3ccc(Cl)cc3Cl)n2)ccc1[N+](=O)[O-]

Procedure:
1 mmol of 2-(2,4-dichlorophenyl)-6-chloro-3-nitropyridine was taken with 2 mmol of (2-aminoethyl)(6-amino-5-nitro(2-pyridyl))amine and 3 mmol of N,N-diisopropylethylamine in 2 ml of DMF at 80° C. for two hours. The reaction mixture was concentrated in vacuo and diluted with water and ethyl acetate. The solution was extracted three times with ethyl acetate, dried over sodium sulfate, and purified by column chromatography eluting with 5-10% methanol/methylene chloride to obtain {2-[(6-amino-5-nitro(2-pyridyl))amino]ethyl}[6-(2,4-dichlorophenyl)-5-nitro(2-pyridyl)]amine.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:7]=[CH:6][S:5][C:4]=1[C:8]([OH:10])=O.F[P-](F)(F)(F)(F)F.Br[P+](N1CCCC1)(N1CCCC1)[N:20]1[CH2:24]CC[CH2:21]1.CNC.C(N(C(C)C)CC)(C)C>C(#N)C>[CH3:21][N:20]([CH3:24])[C:8]([C:4]1[S:5][CH:6]=[CH:7][C:3]=1[O:2][CH3:1])=[O:10]
Reactant: Br[P+](N1CCCC1)(N1CCCC1)N1CCCC1
Reactant: COc1ccsc1C(=O)O
Agent: CNC
Agent: F[P-](F)(F)(F)(F)F
Solvent: CCN(C(C)C)C(C)C
Solvent: CC#N
Product: COc1ccsc1C(=O)N(C)C
Reaction time: 36 h
Yield: 193.6 %

Procedure:
To a suspension of 3-methoxythiophene carboxylic acid (1.84 g, 11.61 mmol), from step A, in 60 mL of acetonitrile at room temperature was added bromotripyrroli-dinophosphonium hexafluorophosphate (PyBrop, 5.40 g, 11.60 mmol), dimethyl amine (2.0 M in THF, 14.5 ml, 29.0 mmol) and diisopropylethyl amine (5.0 mL, 28.63 mmol) successively. After stirred for 1.5 day, the mixture was concentrated under reduced pressure to a yellow oil, which was purified by preparative TLC (CH2Cl2—MeOH=40:1). The silica was extracted with CH2Cl2 and methanol, the extracts were filtered and concentrated to an oil, which was further dried on high vacuum, yielding 4.16 g of N,N-dimethyl 3-methoxythiophene amide (contaminated by PyBrop impurity) (MH+=186.0).
Reaction SMILES: NC1C=CC(C2C=C(C)C=CC=2S(C2C=CC(C)=CC=2C2C=CC(N)=C([N+]([O-])=O)C=2)=O)=CC=1[N+]([O-])=O.[C:37]1([S:43]([C:45]2[CH:50]=[CH:49][C:48]([Cl:51])=[C:47]([N+:52]([O-])=O)[CH:46]=2)=[O:44])[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=1>>[C:37]1([S:43]([C:45]2[CH:50]=[CH:49][C:48]([Cl:51])=[C:47]([NH2:52])[CH:46]=2)=[O:44])[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=1
Reactant: O=[N+]([O-])c1cc(S(=O)c2ccccc2)ccc1Cl
Agent: Cc1ccc(S(=O)c2ccc(C)cc2-c2ccc(N)c([N+](=O)[O-])c2)c(-c2ccc(N)c([N+](=O)[O-])c2)c1
Product: Nc1cc(S(=O)c2ccccc2)ccc1Cl
Yield: 90 %

Procedure:
Following the procedure described in Example 2 but using as a starting material instead of (4-amino-3-nitrophenyl)-4-methylphenyl sulfoxide a corresponding amount of phenyl-(4-chloro-3-nitrophenyl) sulfoxide, the title compound is obtained.
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]([CH:7]=[CH:8][C:9]=1[N:10]1[CH:14]=[N:13][CH:12]=[N:11]1)[CH:5]=O.N1(C2C=C[C:23]([CH:24]=[O:25])=CC=2)C=CC=N1>>[F:1][C:2]1[CH:3]=[C:4](/[CH:5]=[CH:23]/[CH:24]=[O:25])[CH:7]=[CH:8][C:9]=1[N:10]1[CH:14]=[N:13][CH:12]=[N:11]1
Reactant: O=Cc1ccc(-n2cccn2)cc1
Reactant: O=Cc1ccc(-n2cncn2)c(F)c1
Product: O=C/C=C/c1ccc(-n2cncn2)c(F)c1

Procedure:
The title compound was prepared by a procedure analogous to Reference Example 30 by substituting 3-fluoro-4-(1H-1,2,4-triazol-1-yl)benzaldehyde (prepared as described in Reference Example 7) for the 4-(1H-pyrazol-1-yl)-benzaldehyde of Reference Example 30. MS 218 (M+H)+.
Reaction SMILES: [H-].[Na+].[C:3]([C:5]1[CH:6]=[CH:7][C:8]2[NH:9][C:10]3[C:15]([C:16]=2[CH:17]=1)=[CH:14][C:13]([C:18]#[N:19])=[CH:12][CH:11]=3)#[N:4].[CH2:20](Br)[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1.O>CN(C)C=O>[CH2:20]([N:9]1[C:10]2[CH:11]=[CH:12][C:13]([C:18]#[N:19])=[CH:14][C:15]=2[C:16]2[C:8]1=[CH:7][CH:6]=[C:5]([C:3]#[N:4])[CH:17]=2)[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1
Reactant: BrCc1ccccc1
Reactant: N#Cc1ccc2[nH]c3ccc(C#N)cc3c2c1
Agent: [H-]
Agent: [Na+]
Solvent: O
Solvent: CN(C)C=O
Product: N#Cc1ccc2c(c1)c1cc(C#N)ccc1n2Cc1ccccc1
Temperature: 110 °C
Yield: 79.8 %

Procedure:
A slurry of sodium hydride (50% in oil, 960 mg) in 100 ml of dimethylformamide is treated with 3,6-dicyanocarbazole (4.34 g, see Example 1) and heated at 110° C for two hours. The reaction mixture is then treated dropwise with benzylbromide (3.42 g) and heated at 110° C for an additional 18 hours. The reaction mixture is poured into water and extracted several times with dichloromethane. The combined dichloromethane extracts are dried over sodium sulfate and filtered through 200 ml of silica gel to yield 4.9 g of the title compound, melting point 265°-267° C.
Reaction SMILES: [NH:1]1[C:5]2[C:6]3[C:11]([CH2:12][C:4]=2[C:3]([C:13]2[CH:14]=[C:15]([OH:19])[CH:16]=[CH:17][CH:18]=2)=[N:2]1)=[CH:10][CH:9]=[CH:8][CH:7]=3.C1(=O)O[CH2:23][CH2:22][O:21]1.[OH-].[Na+].CN(C)C=O>C(OCC)(=O)C>[NH:1]1[C:5]2[C:6]3[C:11]([CH2:12][C:4]=2[C:3]([C:13]2[CH:14]=[C:15]([CH:16]=[CH:17][CH:18]=2)[O:19][CH2:23][CH2:22][OH:21])=[N:2]1)=[CH:10][CH:9]=[CH:8][CH:7]=3
Reactant: Oc1cccc(-c2n[nH]c3c2Cc2ccccc2-3)c1
Reactant: O=C1OCCO1
Agent: [Na+]
Agent: [OH-]
Solvent: CCOC(C)=O
Solvent: CN(C)C=O
Product: OCCOc1cccc(-c2n[nH]c3c2Cc2ccccc2-3)c1
Temperature: 100 °C

Procedure:
A mixture of 3-(1,4-dihydroindeno[1,2-c]pyrazol-3-yl)phenol (0.29 g), ethylene carbonate (0.11 g), a trace of solid sodium hydroxide (spatula tip of 20-40 mesh beads) and dry dimethylformamide (3 ml) was stirred under nitrogen and heated at 100° C. for 45 minutes. The external temperature was raised to 140° C. and the mixture heated at this temperature for 3.5 hours. The reaction mixture was cooled and diluted with ethyl acetate and the mixture washed with dilute aqueous sodium hydroxide solution and then with water. The organic phase was dried, filtered and evaporated to give a residue which was purified by flash column chromatography on silica using ethyl acetate as the mobile phase. Appropriate fractions were collected, combined and evaporated to give a solid with was triturated with diethyl ether and filtered to give 2-[3-(1,4-dihydroindeno[1,2-c]pyrazol-3-yl)phenoxy]ethanol, m.p. 203-205° C.
Reaction SMILES: [C:1]([O:5][CH2:6][C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1)(=[O:4])[CH:2]=[CH2:3].Br[C:14]1[CH:23]=[CH:22][C:21]2[NH:20][C:19](=[O:24])[N:18]3[C:25](=[O:35])[N:26]([C:28]4[CH:33]=[CH:32][C:31]([CH3:34])=[CH:30][CH:29]=4)[N:27]=[C:17]3[C:16]=2[CH:15]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>CN(C=O)C.CCN(CC)CC.CC([O-])=O.CC([O-])=O.[Pd+2]>[CH3:34][C:31]1[CH:32]=[CH:33][C:28]([N:26]2[C:25](=[O:35])[N:18]3[C:19](=[O:24])[NH:20][C:21]4[CH:22]=[CH:23][C:14](/[CH:3]=[CH:2]/[C:1]([O:5][CH2:6][C:7]5[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=5)=[O:4])=[CH:15][C:16]=4[C:17]3=[N:27]2)=[CH:29][CH:30]=1
Reactant: C=CC(=O)OCc1ccccc1
Reactant: Cc1ccc(-n2nc3c4cc(Br)ccc4[nH]c(=O)n3c2=O)cc1
Agent: [Pd+2]
Agent: CC(=O)[O-]
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: CN(C)C=O
Solvent: CCN(CC)CC
Product: Cc1ccc(-n2nc3c4cc(/C=C/C(=O)OCc5ccccc5)ccc4[nH]c(=O)n3c2=O)cc1
Temperature: 120 °C
Reaction time: 15 h
Yield: 46.8 %

Procedure:
To a stirred solution of benzyl acrylate (44 μg, 0.274 mmol) and 8a (50.6 mg, 0.137 mmol) in a mixture of 8 mL of DMF and 4 mL of NEt3, was added Pd(OAc)2 (3.06 mg, 13.7 mmol) and triphenylphosphine (7.14 mg, 27.4 μmol) in a seal tube. The tube was sealed under argon and the mixture was stirred at 120° C. for 15 h. The mixture was cooled and concentrated to dryness in vacuo and the crude product was precipitated from acetone to give 17 as a white solid (29 mg, 47%). mp: 242° C.
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]=[CH:7][CH:6]=[CH:5]2.[C:12]1([CH:18]([N:20]=[C:21]=[O:22])[CH3:19])[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1>>[C:12]1([CH:18]([NH:20][C:21]([NH:1][C:2]2[CH:3]=[C:4]3[C:9](=[CH:10][CH:11]=2)[N:8]=[CH:7][CH:6]=[CH:5]3)=[O:22])[CH3:19])[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1
Reactant: CC(N=C=O)c1ccccc1
Reactant: Nc1ccc2ncccc2c1
Product: CC(NC(=O)Nc1ccc2ncccc2c1)c1ccccc1

Procedure:
Prepared from 6-aminoquinoline and (+/−)-1-phenylethyl isocyanate. m/z (ES+) 292 (M+H)+.
Reaction SMILES: C([O:4][CH:5](OC(C)C)[C:6]([CH3:26])([CH3:25])[C:7](=[O:24])[CH2:8][C@@H:9]([O:15][C:16]([O:18][CH2:19][C:20]([Cl:23])([Cl:22])[Cl:21])=[O:17])[C@@H:10]([CH3:14])[CH2:11][CH:12]=[CH2:13])(C)C.O.C1(C)C=CC(S(O)(=O)=O)=CC=1.C([O-])(O)=O.[Na+]>C1COCC1.O>[O:24]=[C:7]([CH2:8][C@@H:9]([O:15][C:16]([O:18][CH2:19][C:20]([Cl:21])([Cl:22])[Cl:23])=[O:17])[C@@H:10]([CH3:14])[CH2:11][CH:12]=[CH2:13])[C:6]([CH3:26])([CH3:25])[CH:5]=[O:4]
Reactant: C=CC[C@H](C)[C@@H](CC(=O)C(C)(C)C(OC(C)C)OC(C)C)OC(=O)OCC(Cl)(Cl)Cl
Agent: Cc1ccc(S(=O)(=O)O)cc1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: C1CCOC1
Solvent: O
Product: C=CC[C@H](C)[C@@H](CC(=O)C(C)(C)C=O)OC(=O)OCC(Cl)(Cl)Cl

Procedure:
A mixture of (5R,6S)-1,1-diisopropoxy-5-(2,2,2-trichloroethoxycarbonyloxy)-2,2,6-trimethyl-8-nonen-3-one (4.3 g) and p-toluenesulfonic acid monohydrate (0.45 g) in 100 mL of 3:1 THF/water is heated at reflux for 7 hours. The mixture is cooled and poured into sat. aq. NaHCO3, then extracted with ethyl acetate. The extract is dried over Na2SO4, filtered, and evaporated. The product is purified by chromatography on SiO2.
Reaction SMILES: [F:1][C:2]1[CH:12]=[CH:11][CH:10]=[C:9]([F:13])[C:3]=1[C:4]([N:6]=[C:7]=[O:8])=[O:5].[OH:14][C:15]([C:24]1[CH:30]=[CH:29][C:27]([NH2:28])=[CH:26][CH:25]=1)([C:20]([F:23])([F:22])[F:21])[C:16]([F:19])([F:18])[F:17]>C1(C)C=CC=CC=1>[F:1][C:2]1[CH:12]=[CH:11][CH:10]=[C:9]([F:13])[C:3]=1[C:4]([NH:6][C:7]([NH:28][C:27]1[CH:26]=[CH:25][C:24]([C:15]([OH:14])([C:16]([F:17])([F:18])[F:19])[C:20]([F:21])([F:22])[F:23])=[CH:30][CH:29]=1)=[O:8])=[O:5]
Reactant: Nc1ccc(C(O)(C(F)(F)F)C(F)(F)F)cc1
Reactant: O=C=NC(=O)c1c(F)cccc1F
Solvent: Cc1ccccc1
Product: O=C(NC(=O)c1c(F)cccc1F)Nc1ccc(C(O)(C(F)(F)F)C(F)(F)F)cc1
Temperature: 50 °C
Yield: 88.2 %

Procedure:
0.055 mole of 2,6-difluorobenzoyl isocyanate is dripped into 0.05 mole of 4-(1-hydroxy-1-trifluoromethyl-2,2,2-trifluoroethyl)-aniline in 150 ml of absolute toluene. The temperature rises to 27° C. The mixture is heated for 3 hours at 50° C. and then filtered while hot, and the filter cake is dried under reduced pressure at 50° C. There is obtained 19.5 g (95% of theory) of N-(2,6-difluoro-benzoyl)-N'-[4-(1-hydroxy-1-trifluoromethyl-2,2,2-trifluoroethyl)-phenyl]-urea; m.p.: 205°-207° C.