Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH2:1]([CH:4]([C:8]1([CH3:11])[O:10][CH2:9]1)[C:5](=O)[CH3:6])[CH:2]=[CH2:3]>CCOCC>[CH3:11][C:8]1[O:10][CH:9]=[C:5]([CH3:6])[C:4]=1[CH2:1][CH:2]=[CH2:3]
Reactant: C=CCC(C(C)=O)C1(C)CO1
Solvent: CCOCC
Product: C=CCc1c(C)coc1C
Temperature: 220 °C
Reaction time: 10 h
Yield: 80.5 %

Procedure:
A mixture of 3-allyl-4-methyl-4,5-epoxypentan-2-one (4.5 g) and glass powder (0.90 g) was stirred at a bath temperature of 220° C. for 10 hours in a nitrogen gas stream. After reaction, ether was added to the reaction mass, followed by drying over anhydrous magnesium sulfate. After removing the solvent by evaporation, the residue was distilled under reduced pressure to obtain 3.2 g of 2,4-dimethyl-3-allylfuran as a pale yellow oil.
Reaction SMILES: [N:1]1[CH:6]=[CH:5][CH:4]=[C:3](B(O)O)[CH:2]=1.Br[C:11]1[CH:12]=[C:13]([C:17]2([C:28]3[CH:33]=[CH:32][N:31]=[CH:30][CH:29]=3)[C:25]3[C:20](=[CH:21][CH:22]=[C:23]([F:26])[CH:24]=3)[C:19]([NH2:27])=[N:18]2)[CH:14]=[CH:15][CH:16]=1>>[F:26][C:23]1[CH:24]=[C:25]2[C:20]([C:19]([NH2:27])=[N:18][C:17]2([C:28]2[CH:33]=[CH:32][N:31]=[CH:30][CH:29]=2)[C:13]2[CH:12]=[CH:11][CH:16]=[C:15]([C:3]3[CH:2]=[N:1][CH:6]=[CH:5][CH:4]=3)[CH:14]=2)=[CH:21][CH:22]=1
Reactant: OB(O)c1cccnc1
Reactant: NC1=NC(c2ccncc2)(c2cccc(Br)c2)c2cc(F)ccc21
Product: NC1=NC(c2ccncc2)(c2cccc(-c3cccnc3)c2)c2cc(F)ccc21

Procedure:
The title compound was prepared as described in Example 78 (Scheme #14, N) using pyridin-3-ylboronic acid and 1-(3-bromophenyl)-6-fluoro-1-pyridin-4-yl-1H-isoindol-3-amine (Example 82) (18.5% yield): 1H NMR (DMSO-d6) δ 8.77 (m, 1 H), 8.55 (dd, J=4.80, 1.52 Hz, 1 H), 8.46 (m, 2 H), 7.95 (m, 1 H), 7.87-7.81 (m, 2 H), 7.59 (m, 2 H), 7.47 (m, 1 H), 7.39-7.44 (m, 2 H), 7.37-7.31 (m, 3 H), 6.96 (br s, 2 H); MS (ESI) m/z 381 [M+1]+.
Reaction SMILES: Cl[C:2]1[C:3]([C:8]#[N:9])=[N:4][CH:5]=[CH:6][N:7]=1.Cl.[CH3:11][O:12][C:13](=[O:16])[CH2:14][NH2:15].C(N(CC)CC)C>CCOCC>[C:8]([C:3]1[C:2]([NH:15][CH2:14][C:13]([O:12][CH3:11])=[O:16])=[N:7][CH:6]=[CH:5][N:4]=1)#[N:9]
Reactant: COC(=O)CN
Reactant: N#Cc1nccnc1Cl
Agent: Cl
Solvent: CCN(CC)CC
Solvent: CCOCC
Product: COC(=O)CNc1nccnc1C#N
Temperature: 25 °C
Reaction time: 8 h
Yield: 22.5 %

Procedure:
In 8 ml of ether there was dissolved chlorocyanopyrazine (0.42 g; 0.003 M) prepared in Step B above, after which there was added glycine methyl ester hydrochloride (378 mg; 0.003 M), followed by triethylamine (607 mg, 0.84 ml; 0.006 M). The reaction mixture was stirred at room temperature overnight. The resulting precipitate was filtered, washed twice with ether, and the filtrate concentrated under vacuum, then passed through a silica gel column and eluted with dichloromethane to give the title compound (130 mg).
Reaction SMILES: Cl[C:2]1[C:11]2[C:6](=[CH:7][C:8]3[O:15][CH2:14][CH:13]([CH2:16][O:17][CH3:18])[O:12][C:9]=3[CH:10]=2)[N:5]=[CH:4][N:3]=1.[I:19][C:20]1[CH:21]=[C:22]([CH:24]=[CH:25][CH:26]=1)[NH2:23]>>[I:19][C:20]1[CH:21]=[C:22]([NH:23][C:2]2[C:11]3[C:6](=[CH:7][C:8]4[O:15][CH2:14][CH:13]([CH2:16][O:17][CH3:18])[O:12][C:9]=4[CH:10]=3)[N:5]=[CH:4][N:3]=2)[CH:24]=[CH:25][CH:26]=1
Reactant: COCC1COc2cc3ncnc(Cl)c3cc2O1
Reactant: Nc1cccc(I)c1
Product: COCC1COc2cc3ncnc(Nc4cccc(I)c4)c3cc2O1
Yield: 72.3 %

Procedure:
The titled compound (260 mg, 94%, m.p. 175-177° C.) was prepared in a similar manner as in Example 8, except for employing 4-chloro-7-methoxymethyl-[1,4]dioxano[2,3-g]quinazoline (175 mg, 0.8 mmol) and 3-iodoaniline (350 mg, 1.6 mmol).
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.[CH2:12]([N:19]=[C:20]=[O:21])[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1>>[CH2:12]([NH:19][C:20]([NH: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)=[O:21])[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1
Reactant: Nc1ccc2ncccc2c1
Reactant: O=C=NCc1ccccc1
Product: O=C(NCc1ccccc1)Nc1ccc2ncccc2c1

Procedure:
Prepared from 6-aminoquinoline and benzyl isocyanate. m/z (ES+) 278 (M+H)+.
Reaction SMILES: [Br:1][C:2]1[CH:11]=[C:10]2[C:5]([N:6]=[CH:7][C:8](=O)[NH:9]2)=[CH:4][CH:3]=1.O=P(Cl)(Cl)[Cl:15]>C(Cl)(Cl)Cl.C(O)(C)C>[Br:1][C:2]1[CH:11]=[C:10]2[C:5]([N:6]=[CH:7][C:8]([Cl:15])=[N:9]2)=[CH:4][CH:3]=1
Reactant: O=P(Cl)(Cl)Cl
Reactant: O=c1cnc2ccc(Br)cc2[nH]1
Solvent: ClC(Cl)Cl
Solvent: CC(C)O
Product: Clc1cnc2ccc(Br)cc2n1
Yield: 58 %

Procedure:
Heat benzene-1,2-diamine (7.5 g, 69 mmol) and oxo-acetic acid ethyl ester (20 mL) in ethanol (100 mL) at 120° C. for 18 h. Cool, filter the resulting precipitate, and wash with dry ether to give 1H-quinoxalin-2-one (6.7 g). Dissolve 1H-quinoxalin-2-one in acetic acid (300 mL), add bromine (5 mL), and stir the reaction mixture for 1 h. Filter the resulting crystals and wash with ether to afford 7-bromo-1H-quinoxalin-2-one (7.2 g). Reflux 7-bromo-1H-quinoxalin-2-one in POCl3 (30 mL) for 18 h. Remove POCl3 in vacuo, dissolve the product in 3:1 chloroform/isopropyl alcohol, and wash the organic phase with saturated sodium bicarbonate. Dry over sodium sulfate and purify by silica gel flash chromatography eluting with dichloromethane to 10% methanol/90% dichloromethane to afford the title compound as a yellow solid (4.5 g, 58%). MS (electrospray, m/z) 243.0 and 245.0 (M+1).
Reaction SMILES: Cl.[CH:2]1([NH:8][OH:9])[CH2:7][CH2:6][CH2:5][CH2:4][CH2:3]1.C(N(CC)CC)C.[CH3:17][C:18]1[O:19][CH:20]=[CH:21][C:22]=1[C:23](Cl)=[O:24]>C1C=CC=CC=1>[CH:2]1([N:8]([C:23]([C:22]2[CH:21]=[CH:20][O:19][C:18]=2[CH3:17])=[O:24])[OH:9])[CH2:7][CH2:6][CH2:5][CH2:4][CH2:3]1
Reactant: Cc1occc1C(=O)Cl
Reactant: ONC1CCCCC1
Agent: Cl
Solvent: c1ccccc1
Solvent: CCN(CC)CC
Product: Cc1occc1C(=O)N(O)C1CCCCC1
Reaction time: 1 h

Procedure:
57 parts (by weight) of N-cyclohexylhydroxylamine hydrochloride is added to 800 parts of benzene; 71 parts of triethylamine is then introduced into this mixture. After the mixture has been stirred for 1 hour, a solution of 50 parts of 2-methylfuran-3-carboxylic chloride in 100 parts of benzene is dripped in at room temperature. After the mixture has been stirred for 3 hours the precipitate is filtered and washed with benzene. The filtrate is washed with water, dried over sodium sulfate and evaporated. The crystalline residue is recrystallized from cyclohexane. There is obtained 33 parts of N-cyclohexyl-2-methylfuran-3-hydroxamic acid, m.p.: 108°-110° C.
Reaction SMILES: C(=O)([O-])[O-].[Cs+].[Cs+].[Br:7][C:8]1[N:9]([CH2:18][C:19]#[C:20][CH3:21])[C:10]2[C:15](=[O:16])[NH:14][N:13]=[CH:12][C:11]=2[N:17]=1.Cl[CH2:23][C:24]1[N:33]=[C:32]([CH3:34])[C:31]2[C:26](=[CH:27][CH:28]=[CH:29][CH:30]=2)[N:25]=1>CN(C)C=O.O>[Br:7][C:8]1[N:9]([CH2:18][C:19]#[C:20][CH3:21])[C:10]2[C:15](=[O:16])[N:14]([CH2:23][C:24]3[N:33]=[C:32]([CH3:34])[C:31]4[C:26](=[CH:27][CH:28]=[CH:29][CH:30]=4)[N:25]=3)[N:13]=[CH:12][C:11]=2[N:17]=1
Reactant: CC#CCn1c(Br)nc2cn[nH]c(=O)c21
Reactant: Cc1nc(CCl)nc2ccccc12
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: O
Solvent: CN(C)C=O
Product: CC#CCn1c(Br)nc2cnn(Cc3nc(C)c4ccccc4n3)c(=O)c21
Temperature: 80 °C
Reaction time: 1 h

Procedure:
489 mg (1.5 mol) cesium carbonate were added to a solution of 300 mg (1.12 mmol) 2-bromo-3-(but-2-ynyl)-3,5-dihydro-imidazo[4,5-d]pyridazin-4-one and 344 mg (1.35 mmol) 2-chloromethyl-4-methyl-quinazoline in 4 ml of dimethylformamide and this mixture was stirred for 1 h under an argon atmosphere at 80° C. Then the mixture was diluted with 10 ml of water, the solution was cooled to approx. 10° C., the precipitate formed was suction filtered and dried and purified by column chromatography (silica gel; eluant: dichloromethane/ethanol 1:0->19:1).
Reaction SMILES: [CH3:1][O:2][C:3](=[O:15])[C:4]1[CH:9]=[CH:8][C:7]([OH:10])=[C:6]([C:11]([CH3:14])([CH3:13])[CH3:12])[CH:5]=1.[Si:16](Cl)([C:19]([CH3:22])([CH3:21])[CH3:20])([CH3:18])[CH3:17].N1C=CN=C1>CN(C=O)C>[C:11]([C:6]1[CH:5]=[C:4]([CH:9]=[CH:8][C:7]=1[O:10][Si:16]([C:19]([CH3:22])([CH3:21])[CH3:20])([CH3:18])[CH3:17])[C:3]([O:2][CH3:1])=[O:15])([CH3:12])([CH3:14])[CH3:13]
Reactant: COC(=O)c1ccc(O)c(C(C)(C)C)c1
Reactant: CC(C)(C)[Si](C)(C)Cl
Agent: c1c[nH]cn1
Solvent: CN(C)C=O
Product: COC(=O)c1ccc(O[Si](C)(C)C(C)(C)C)c(C(C)(C)C)c1
Yield: 78.8 %

Procedure:
According to example 183, 5.00 g of methyl-3-tert-butyl-4-hydroxybenzoate was silylated using 4.34 g of tert-butyldimethylsilyl chloride, 3.59 g of imidazole, and 70 mL of anhydrous DMF. The crude product was purified by flash chromatography on silica gel (9:1 hexane:EtOAc) to afford 6.1 g (79%) of methyl 3-tert-butyl-4-((tert-butyldimethylsilyl)oxy)benzoate as a clear liquid.
Reaction SMILES: [C:1](Cl)(=[O:17])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH3:16].C1COCC1.[N:24]#[C:25][NH2:26].[Na].Cl>O>[C:1]([NH:26][C:25]#[N:24])(=[O:17])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH3:16]
Reactant: N#CN
Reactant: CCCCCCCCCCCCCCCC(=O)Cl
Agent: Cl
Agent: [Na]
Solvent: C1CCOC1
Solvent: O
Product: CCCCCCCCCCCCCCCC(=O)NC#N
Reaction time: 43 h
Yield: 96.3 %

Procedure:
A solution of palmitoyl chloride (5.5 g, 0.020 mol) in 50 ml of freshly distilled dry THF was added drop-wise to a suspension of sodium cyanamide (3.84 g. 0.060 mol) in 150 ml of freshly distilled dry THF at ice bath temperature. After the addition, the ice bath was removed and the reaction was allowed to proceed at 25° C for 43 hours. The solids that formed were filtered to yield 8.48 g of waxy solid residue. The residue was ground to a fine powder and stirred in 150 ml of distilled water at ice bath temperature. The resulting soapy suspension (pH 11) was acidified to pH 2 with 10% HCl, then filtered and air-dried to give 5.4 g (96.3% yield) of crude 6 as a white solid. This was dissolved in warm THF and the mixture filtered. The filtrate was concentrated in vacuo until the solution became slightly turbid. This material was crystallized from THF/petroleum ether to yield 3.6 g (crop 1) of white powder. The filtrate was concentrated and crystallized in the same fashion to yield additional 0.6 g (crop 2) of white powder (74.8% total yield), mp 62°-65° C. TLC: Rf =0.68 in ethyl acetate/petroleum ether/glacial acetic acid (10:20:1); IR (Nujol, cm-1) 3230 (NH), 2250 (C≡N), 1740 (C=O); NMR (Silanor C, δ from TMS) 1.3-1.6 (t, --CH2 --CH2 --C=O), 1-1.8 (m, --(CH2)13 --), 0.8-1 (t, CH3 --CH2 --); Anal. Calcd for C17H32N2O: C, 72.81; H, 11.50; N, 9.99. Found: C, 72.69; H, 11.65; N, 9.68.
Reaction SMILES: [CH:1]1([C:6]2([CH3:19])[CH2:14][C:13]3[C:8](=[C:9]([Cl:17])[C:10]([Cl:16])=[C:11]([OH:15])[CH:12]=3)[C:7]2=[O:18])[CH2:5][CH2:4][CH2:3][CH2:2]1.C(=O)([O-])[O-].[K+].[K+].Br[CH2:27][CH2:28][CH:29]=[CH2:30].O>CN(C)C=O>[Cl:16][C:10]1[C:9]([Cl:17])=[C:8]2[C:13]([CH2:14][C:6]([CH:1]3[CH2:2][CH2:3][CH2:4][CH2:5]3)([CH3:19])[C:7]2=[O:18])=[CH:12][C:11]=1[O:15][CH2:30][CH2:29][CH:28]=[CH2:27]
Reactant: CC1(C2CCCC2)Cc2cc(O)c(Cl)c(Cl)c2C1=O
Reactant: C=CCCBr
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CN(C)C=O
Product: C=CCCOc1cc2c(c(Cl)c1Cl)C(=O)C(C)(C1CCCC1)C2
Temperature: 60 °C

Procedure:
2-Cyclopentyl-6,7-dichloro-2,3-dihydro-2-methyl-5-hydroxy-1H-inden-1-one (12 gm., 0.04 mole) is dissolved in dimethylformamide (30 m.) and treated with potassium carbonate (5.5 gm., 0.04 mole). The mixture is stirred and heated on a steam bath for 30 minutes and 4-bromo-1-butene (5.5 gm., 0.04 mole) is added and the mixture stirred and heated at 60° C. for 24 hours. The reaction mixture is poured into water (300 ml.) and, after standing, the product removed by filtration, dried and recrystallized from petroleum ether. The yield is 11.5 gm., m.p. 63°-65° C.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([N:9]2[C:13]([C:14]3[CH:19]=[CH:18][C:17]([N+:20]([O-])=[O:21])=[CH:16][CH:15]=3)=[CH:12][CH:11]=[N:10]2)=[CH:5][CH:4]=1.[Cl:23][C:24]1[CH:29]=[CH:28][C:27]([CH2:30]C#N)=[CH:26][CH:25]=1>>[Cl:23][C:24]1[CH:29]=[CH:28][C:27]([C:30]2[O:21][N:20]=[C:17]3[CH:18]=[CH:19][C:14]([C:13]4[N:9]([C:6]5[CH:7]=[CH:8][C:3]([O:2][CH3:1])=[CH:4][CH:5]=5)[N:10]=[CH:11][CH:12]=4)=[CH:15][C:16]=23)=[CH:26][CH:25]=1
Reactant: N#CCc1ccc(Cl)cc1
Reactant: COc1ccc(-n2nccc2-c2ccc([N+](=O)[O-])cc2)cc1
Product: COc1ccc(-n2nccc2-c2ccc3noc(-c4ccc(Cl)cc4)c3c2)cc1

Procedure:
The title compound, light yellow solid (85 mg, 63%), MS (ISP) m/z=402.3 [(M+H)+], mp 177° C., was prepared in accordance with the general method of example 1 from 1-(4-methoxy-phenyl)-5-(4-nitro-phenyl)-1H-pyrazole (intermediate G) (100 mg, 353 μmol) and commercially available 2-(4-chloro-phenyl)-acetonitrile.
Reaction SMILES: [CH3:1][O:2][C@H:3]1[CH2:8][CH2:7][C@H:6]2[C@H:9]3[C@H:19]([CH2:20][CH2:21][C@:4]12[CH3:5])[C@:17]1([CH3:18])[C@H:12]([CH2:13][C:14](=[O:22])[CH2:15][CH2:16]1)[CH2:11][CH2:10]3.[C:23](O)(=[O:30])[C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1.C(OC(=O)C1C=CC=CC=1)(=O)C1C=CC=CC=1.C(OC(=O)C)(=O)C>>[C:23]([CH:15]1[CH2:16][C@@:17]2([CH3:18])[C@@H:12]([CH2:11][CH2:10][C@@H:9]3[C@@H:19]2[CH2:20][CH2:21][C@@:4]2([CH3:5])[C@H:6]3[CH2:7][CH2:8][C@@H:3]2[O:2][CH3:1])[CH2:13][C:14]1=[O:22])(=[O:30])[C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1
Reactant: CO[C@H]1CC[C@H]2[C@@H]3CC[C@H]4CC(=O)CC[C@]4(C)[C@H]3CC[C@]12C
Reactant: O=C(O)c1ccccc1
Agent: O=C(OC(=O)c1ccccc1)c1ccccc1
Solvent: CC(=O)OC(C)=O
Product: CO[C@H]1CC[C@H]2[C@@H]3CC[C@H]4CC(=O)C(C(=O)c5ccccc5)C[C@]4(C)[C@H]3CC[C@]12C

Procedure:
Following the general procedure of U.S. Pat. No. 3,135,743, Example 12, but starting with 17β-methoxy-5α-androstan-3-one and using benzoic acid and benzoic acid anhydride in place of acetic acid and acetic anhydride, 2-benzoyl-17β-methoxy-5α-androstan-3-one is obtained.
Reaction SMILES: [CH2:1]=[CH:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1>C1C=CC=CC=1>[C:3]1([CH:2]([C:3]2[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=2)[CH3:1])[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1
Reactant: C=Cc1ccccc1
Solvent: c1ccccc1
Product: CC(c1ccccc1)c1ccccc1
Yield: 25 %

Procedure:
One known synthesis of this odorant is based on the Friedel-Crafts reaction of styrene with benzene (see Spilker and Schade, Chem. Berichte, 65 (1932), 1686. The product 1,1-diphenylethane was obtained in only 25% yield. Other procedures described in the literature, for example the reaction of benzyl chloride with toluene and cupric chlorides as catalysts (U.S. Pat. No. 3,679,760) or the oxidative coupling of ethylbenzene and benzene with a catalyst consisting of aluminum and cupric chlorides (U.S. Pat. No. 3,631,211) produce only low yields and/or require costly starting materials, so that industrial use is not practical.
Reaction SMILES: Br[C:2]1[N:3]=[C:4]([NH2:12])[CH:5]=[C:6]2[C:11]=1[N:10]=[CH:9][CH:8]=[CH:7]2.C([O-])([O-])=O.[K+].[K+].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[F:38][C:39]1[CH:40]=[CH:41][C:42]([O:48][CH3:49])=[C:43](B(O)O)[CH:44]=1>C1(C)C=CC=CC=1.C(OCC)(=O)C.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].CN(C=O)C>[F:38][C:39]1[CH:44]=[CH:43][C:42]([O:48][CH3:49])=[C:41]([C:2]2[N:3]=[C:4]([NH2:12])[CH:5]=[C:6]3[C:11]=2[N:10]=[CH:9][CH:8]=[CH:7]3)[CH:40]=1
Reactant: Nc1cc2cccnc2c(Br)n1
Reactant: COc1ccc(F)cc1B(O)O
Agent: [Pd]
Agent: O=C(/C=C/c1ccccc1)/C=C/c1ccccc1
Agent: O=C([O-])[O-]
Solvent: CCOC(C)=O
Solvent: Cc1ccccc1
Solvent: CN(C)C=O
Product: COc1ccc(F)cc1-c1nc(N)cc2cccnc12
Temperature: 100 °C
Reaction time: 3.5 h

Procedure:
To a stirred solution of 8-bromo-[1,7]naphthyridin-6-ylamine (1.70 g) in a mixture of toluene (7 ml), DMF (11 ml) and aqueous K2CO3 (2.31 g in 5 ml water) is added bis(dibenzylideneacetone)palladium (174 mg), triphenylphosphine (158 mg) and 5-fluoro-2-methoxyphenylboronic acid (1.38 g). The mixture is stirred for 3.5 hours at 100° C., then diluted with ethyl acetate and filtered through Celite. The ethyl acetate solution is washed with 2N NaOH and water, dried over magnesium sulphate, then concentrated to afford the title compound. MS: APCI 270.0 MH+.
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[C:6]([Br:8])[CH:5]=[CH:4][C:3]=1[NH-:9].[O:10]=[C:11]1[C:23]2[CH:22]=[CH:21][CH:20]=[C:19]([C:24](O)=O)[C:18]=2[C:17]2[C:12]1=[CH:13][CH:14]=[CH:15][CH:16]=2>C(O)(=O)C>[Br:8][C:6]1[CH:5]=[CH:4][C:3]2[N:9]=[C:24]([C:19]3[C:18]4[C:17]5[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=5)[C:11](=[O:10])[C:23]=4[CH:22]=[CH:21][CH:20]=3)[NH:1][C:2]=2[CH:7]=1
Reactant: O=C(O)c1cccc2c1-c1ccccc1C2=O
Reactant: [NH-]c1ccc(Br)cc1N
Solvent: CC(=O)O
Product: O=C1c2ccccc2-c2c1cccc2-c1nc2ccc(Br)cc2[nH]1

Procedure:
A mixture of 1.61 g of (2-amino-4-bromophenyl)amide of 9-oxo-9H-fluorene-4-carboxylic acid in 80 ml of glacial acetic acid is refluxed for 2.5 hours. Allow to return to ambient temperature and evaporate the reaction medium to dryness under vacuum. The residue is taken up with 50 ml of dichloromethane, and the organic phase is washed with twice 50 ml of a saturated solution of sodium bicarbonate and 50 ml of a saturated solution of sodium chloride. After drying over magnesium sulphate, the organic phase is evaporated to dryness under vacuum. The residue is chromatographed on silica gel, eluting with a mixture of methanol and dichloromethane (5/95 by volume). In this way, we obtain 1.5 g of 4-(6-bromo-1H-benzimidazol-2-yl)-9H-fluoren-9-one, with the following characteristics:
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][N:5]=[C:4]([NH:8]C(=O)OC(C)(C)C)[C:3]=1[C:16]#[C:17][CH:18]1[CH2:23][CH2:22][CH2:21][CH2:20][CH2:19]1.CC(C)([O-])C.[K+].C1OCCOCCOCCOCCOCCOC1>C1(C)C=CC=CC=1>[Cl:1][C:2]1[CH:7]=[CH:6][N:5]=[C:4]2[NH:8][C:17]([CH:18]3[CH2:23][CH2:22][CH2:21][CH2:20][CH2:19]3)=[CH:16][C:3]=12
Reactant: CC(C)(C)OC(=O)Nc1nccc(Cl)c1C#CC1CCCCC1
Agent: C1COCCOCCOCCOCCOCCO1
Agent: CC(C)(C)[O-]
Agent: [K+]
Solvent: Cc1ccccc1
Product: Clc1ccnc2[nH]c(C3CCCCC3)cc12
Temperature: 85 °C

Procedure:
A solution of Example 98A (870 mg, 2.60 mmol) in 20 mL toluene was treated with potassium tert-butoxide (729 mg, 6.50 mmol) and 18-crown-6 (68.7 mg, 0.260 mmol) and the mixture was heated at 65° C. for 6 hours and at 85° C. overnight. The cooled mixture was partitioned between ethyl acetate and water. The layers were separated and the aqueous layer was extracted with ethyl acetate (twice). The combined organic extracts were rinsed with water (once) and brine (twice), dried over magnesium sulfate, filtered, and concentrated. The residue was suspended in diethyl ether and the solids were collected and rinsed with diethyl ether to afford the title compound. MS (DCI) m/e 235/237 (M+H)+.
Reaction SMILES: [Cl:1][C:2]1[CH:18]=[CH:17][C:5]([O:6][CH2:7][C:8](=[O:16])[C:9]([CH3:15])([CH3:14])[CH:10]([Br:13])[CH2:11][Br:12])=[CH:4][CH:3]=1.[Br:19]Br>C(Cl)(Cl)Cl>[Cl:1][C:2]1[CH:18]=[CH:17][C:5]([O:6][CH:7]([Br:19])[C:8](=[O:16])[C:9]([CH3:14])([CH3:15])[CH:10]([Br:13])[CH2:11][Br:12])=[CH:4][CH:3]=1
Reactant: BrBr
Reactant: CC(C)(C(=O)COc1ccc(Cl)cc1)C(Br)CBr
Solvent: ClC(Cl)Cl
Product: CC(C)(C(=O)C(Br)Oc1ccc(Cl)cc1)C(Br)CBr
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 99.7 %

Procedure:
107 g (0.269 mole) of 1-(4-chlorophenoxy)-4,5-dibromo-3,3-dimethyl-2-pentanone are dissolved in 400 ml of chloroform. 43 g (0.269 mole) of bromine are added dropwise at room temperature such that the solution is always decolorized. The mixture is then subsequently stirred at room temperature for 30 minutes, washed with water, dried over sodium sulphate and concentrated. 128 g (99% of theory) of 1-(4-chlorophenoxy)-3,3-dimethyl-1,4,5-tribromo-2-pentanone of refractive index nD20 1.5472 are obtained. ##STR107##
Reaction SMILES: CN(C)CC[N:5](C)[C:6]1[CH:7]=[C:8]([N:14]2[C:18](S)=NN=[C:15]2[C:20]2C=C(C(C)C)C(O)=C[C:21]=2O)[CH:9]=[CH:10][C:11]=1OC>CO.CCOC(C)=O.[Pd]>[CH3:18][N:14]([CH2:15][CH2:20][CH3:21])[C:8]1[CH:9]=[CH:10][CH:11]=[C:6]([NH2:5])[CH:7]=1
Reactant: COc1ccc(-n2c(S)nnc2-c2cc(C(C)C)c(O)cc2O)cc1N(C)CCN(C)C
Agent: [Pd]
Solvent: CCOC(C)=O
Solvent: CO
Product: CCCN(C)c1cccc(N)c1
Yield: 116.9 %

Procedure:
A solution of 9.0 g (40.1 mmol mmol) of (2-Methoxy-5-nitro-phenyl)-methyl-propyl-amine (4) in 200 mL of MeOH/EtOAc (1:1) containing 5% w/w of Pd—C (10%) was subjected to hydrogenation (1 atm, balloon) overnight. The contents of the flask were passed through a short pad of celite and washed with EtOAc. The filtrate was evaporated under reduced pressure to give 7.7 g (92%) of crude amine 4-Methoxy-N3-methyl-N3-propyl-benzene-1,3-diamine (5) of an oil.
Reaction SMILES: [Br:1][CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][C:11]([OH:13])=[O:12].[CH3:14]O>S(=O)(=O)(O)O>[CH3:14][O:12][C:11](=[O:13])[CH2:10][CH2:9][CH2:8][CH2:7][CH2:6][CH2:5][CH2:4][CH2:3][CH2:2][Br:1]
Reactant: CO
Reactant: O=C(O)CCCCCCCCCBr
Agent: O=S(=O)(O)O
Product: COC(=O)CCCCCCCCCBr

Procedure:
A solution of 10-bromodecanoic acid (5 g) in methanol (60 ml) and concentrated sulphuric acid (3 drops) was refluxed for 20 hours.
Reaction SMILES: [CH3:1][C:2](=[CH2:7])[C:3]#[C:4][CH2:5][OH:6].[CH3:8][SiH:9]([CH3:14])N[SiH](C)C.CC([O-])(C)C.[K+]>>[CH3:8][Si:9]1([CH3:14])[C:3]([C:2]([CH3:1])=[CH2:7])=[CH:4][CH2:5][O:6]1
Reactant: C=C(C)C#CCO
Reactant: C[SiH](C)N[SiH](C)C
Agent: CC(C)(C)[O-]
Agent: [K+]
Product: C=C(C)C1=CCO[Si]1(C)C
Yield: 115.7 %

Procedure:
Using 4-methylpent-4-en-2-yn-1-ol (1.792 g, 18.64 mmol), 1,1,3,3-tetramethyldisilazane (1.504 g, 11.28 mmol) and KOtBu (0.217 g, 1.934 mmol) according to the above general procedure resulted a clear brown colored crude reaction mixture which upon purification by column chromatography yielded 10a as a clear colorless oil (2.014 g, 13.05 mmol, 70.0%): Rf 0.68 (pentane/Et2O, 3:1); 1H NMR (500 MHz, CDCl3) δ 6.60 (as, 1H, H-4), 4.99 (s, 1H, H-8′), 4.82 (s, 1H, H-8″), 4.66 (s, 2H, H-5), 1.93 (s, 3H, H-9), 0.33 (as, 6H, H-6); 13C NMR (300 MHz, CDCl3) δ 142.2 (C-3), 141.3 (C-7), 141.2 (C-4), 115.7 (C-8), 71.9 (C-5), 20.4 (C-9), 0.45 (C-6); HRMS calcd for C8H14OSi (M+) 154.0814. found 154.0813.
Reaction SMILES: Br[C:2]1[CH:3]=[C:4]([CH:8]2[O:12][CH2:11][CH2:10][O:9]2)[CH:5]=[CH:6][CH:7]=1.BrCCBr.[Mg].[CH3:18][C:19]1[S:23][C:22]([CH:24]=[O:25])=[CH:21][CH:20]=1>O.C1COCC1>[O:9]1[CH2:10][CH2:11][O:12][CH:8]1[C:4]1[CH:3]=[C:2]([CH:24]([C:22]2[S:23][C:19]([CH3:18])=[CH:20][CH:21]=2)[OH:25])[CH:7]=[CH:6][CH:5]=1
Reactant: Brc1cccc(C2OCCO2)c1
Reactant: Cc1ccc(C=O)s1
Agent: [Mg]
Solvent: O
Solvent: BrCCBr
Solvent: C1CCOC1
Product: Cc1ccc(C(O)c2cccc(C3OCCO3)c2)s1
Temperature: 0 °C
Yield: 50.2 %

Procedure:
To a solution of THF (20 mL), 2-(3-bromophenyl)-1,3-dioxolane (2.7 g) and 1,2-dibromoethane (150 mg) was added magnesium (270 mg), which was heated to reflux for 10 minutes. The reaction mixture was cooled to 0° C., and a solution of 5-methyl-2-thiophencarbaldehyde (1.0 g) and THF (5 mL) was added thereto under stirring. The reaction solution was returned to room temperature and stirred for 10 minutes. Water was added to the reaction solution, which was then extracted with ethyl acetate. The solvent was evaporated from the organic layer under a reduced pressure, and the residue was purified by silica gel chromatography (heptane:ethyl acetate=2:1) to obtain the titled compound (1.1 g).
Reaction SMILES: [CH3:1][C:2]1[C:3]([N+:12]([O-])=O)=[C:4]([CH:6]=[CH:7][C:8]=1[N+:9]([O-:11])=[O:10])[NH2:5].O.O.O.O.O.O.O.O.O.[S-2].[Na+].[Na+]>C(O)C.O>[NH2:12][C:3]1[C:4]([NH2:5])=[CH:6][CH:7]=[C:8]([N+:9]([O-:11])=[O:10])[C:2]=1[CH3:1]
Reactant: Cc1c([N+](=O)[O-])ccc(N)c1[N+](=O)[O-]
Agent: [Na+]
Agent: [S-2]
Solvent: CCO
Solvent: O
Product: Cc1c([N+](=O)[O-])ccc(N)c1N
Temperature: 0 °C

Procedure:
To a solution of 30 g of 3-methyl-2,4-dinitroaniline in 750 mL of boiling ethanol is added dropwise over 90 minutes a solution of 109.6 g of sodium sulfide nonahydrate in 750 mL of water. At the end of the addition, the mixture is heated to reflux for 30 minutes then poured into ice (2000 g) and allowed to stand until all the ice has melted. The mixture is then extracted with methylene chloride and the organic layer is dried over magnesium sulfate and rotary evaporated. The residue is purified by flash column chromatography on silica gel, eluting with methylene chloride to afford 2,3-diamino-6-nitrotoluene as an orange solid.