Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [OH-].[K+].[CH2:3]([O:13][C:14]1[CH:19]=[CH:18][C:17]([C:20]2[O:21][C:22]3[CH:28]=[CH:27][C:26]([O:29]C(=O)C)=[CH:25][C:23]=3[N:24]=2)=[CH:16][CH:15]=1)[CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH3:12]>C(O)C>[CH2:3]([O:13][C:14]1[CH:19]=[CH:18][C:17]([C:20]2[O:21][C:22]3[CH:28]=[CH:27][C:26]([OH:29])=[CH:25][C:23]=3[N:24]=2)=[CH:16][CH:15]=1)[CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH3:12]
Reactant: CCCCCCCCCCOc1ccc(-c2nc3cc(OC(C)=O)ccc3o2)cc1
Agent: [K+]
Agent: [OH-]
Solvent: CCO
Product: CCCCCCCCCCOc1ccc(-c2nc3cc(O)ccc3o2)cc1
Temperature: 60 °C
Reaction time: 0.5 h
Yield: 19.3 %

Procedure:
In a 50 ml-round-bottomed flask, 1.50 g of (3.81 mM) of 2-(4-decyloxyphenyl)-5-acetylbenzoxazole was dissolved in 10 ml of dichloromethane, followed by successive addition of 0.66 g of (3.82 mM) of m-chloroperbenzoic acid and 0.40 g (4.00 mM) of potassium hydrogencarbonate and heat-refluxing for 7 hours and 40 minutes under stirring. After cooling to room temperature, 0.33 g (1.91 mM) of m-chloroperbenzoic acid and 0.20 g (2.00 mM) of potassium hydrogencarbonate was successively added, followed by heat-refluxing for 12 hours under stirring. After the reaction, the insoluble was filtered off and the filtrate was subjected to reduced pressure distillation to obtain a residue. The residue was purified by silica gel column chromatography (eluent: toluene/ethyl acetate=100/1) to obtain 2-(4-decyloxyphenyl)-5-acetoxybenzoxazole. Then, 0.51 g (7.73 mM) of potassium hydroxide was dissolved in 50 ml of ethanol under heating. To the solution, the above-prepared 2-(4-decyloxyphenyl)-5-acetoxybenzoxazole was added, followed by stirring for 30 minutes at about 60° C. After the reaction, ethanol in the reaction mixture was distilled off under reduced pressure. To the resultant residue, 50 ml of water was added, followed by addition of 0.7 ml of hydrochloric acid under stirring on an ice bath to precipitate a crystal. The crystal was recovered by filtration and washed with water, followed by recrystallization from methanol to obtain 0.27 g of 2-(4-decyloxyphenyl)-5-hydroxybenzoxazole (Yield: 19.3%).
Reaction SMILES: O[CH2:2][CH2:3][CH2:4][CH2:5][CH:6]1[C:11](=[O:12])[NH:10][C:9]2[CH:13]=[CH:14][CH:15]=[CH:16][C:8]=2[S:7]1.S(Cl)([Cl:19])=O>>[Cl:19][CH2:2][CH2:3][CH2:4][CH2:5][CH:6]1[C:11](=[O:12])[NH:10][C:9]2[CH:13]=[CH:14][CH:15]=[CH:16][C:8]=2[S:7]1
Reactant: O=S(Cl)Cl
Reactant: O=C1Nc2ccccc2SC1CCCCO
Product: O=C1Nc2ccccc2SC1CCCCCl
Yield: 59 %

Procedure:
By a process similar to that in Reference Example 13-(2), 2-(4-hydroxybutyl)-2H-1,4-benzothiazin-3(4H)-one was allowed to react with thionyl chloride to obtain 2-(4-chlorobutyl)-2H-1,4-benzothiazin-3(4H)-one. The yield was 59.0%. m.p. 111°-112° C. (recrystallized from ethyl acetate-hexane).
Reaction SMILES: [CH2:1]([C:8]1[CH:9]=[N:10][C:11]2[C:16]([C:17]=1[C:18]1[CH:19]=[C:20]([NH2:24])[CH:21]=[CH:22][CH:23]=1)=[CH:15][CH:14]=[CH:13][C:12]=2[C:25]([F:28])([F:27])[F:26])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[O:29]([C:31]1[CH:32]=[C:33]([CH:36]=[C:37]([O:39][CH3:40])[CH:38]=1)[CH:34]=O)[CH3:30]>>[CH2:1]([C:8]1[CH:9]=[N:10][C:11]2[C:16]([C:17]=1[C:18]1[CH:19]=[C:20]([NH:24][CH2:34][C:33]3[CH:36]=[C:37]([O:39][CH3:40])[CH:38]=[C:31]([O:29][CH3:30])[CH:32]=3)[CH:21]=[CH:22][CH:23]=1)=[CH:15][CH:14]=[CH:13][C:12]=2[C:25]([F:28])([F:26])[F:27])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: Nc1cccc(-c2c(Cc3ccccc3)cnc3c(C(F)(F)F)cccc23)c1
Reactant: COc1cc(C=O)cc(OC)c1
Product: COc1cc(CNc2cccc(-c3c(Cc4ccccc4)cnc4c(C(F)(F)F)cccc34)c2)cc(OC)c1

Procedure:
This compound was prepared according to the procedure of example 66, substituting 3-(3-benzyl-8-trifluoromethyl-quinolin-4-yl)-phenylamine and 3,5 dimethoxylbenzaldehyde. MS (ESI) m/z 522.
Reaction SMILES: C([O:3][C:4](=[O:27])[CH2:5][N:6]1[C:14]2[C:9](=[CH:10][CH:11]=[CH:12][CH:13]=2)[C:8]2([C:18]3=[CH:19][C:20]4[O:24][CH2:23][O:22][C:21]=4[CH:25]=[C:17]3[O:16][CH2:15]2)[C:7]1=[O:26])C.O.[OH-].[Li+].Cl>C1COCC1.O>[O:26]=[C:7]1[C:8]2([C:18]3=[CH:19][C:20]4[O:24][CH2:23][O:22][C:21]=4[CH:25]=[C:17]3[O:16][CH2:15]2)[C:9]2[C:14](=[CH:13][CH:12]=[CH:11][CH:10]=2)[N:6]1[CH2:5][C:4]([OH:27])=[O:3]
Reactant: CCOC(=O)CN1C(=O)C2(COc3cc4c(cc32)OCO4)c2ccccc21
Agent: Cl
Agent: [Li+]
Agent: [OH-]
Solvent: C1CCOC1
Solvent: O
Product: O=C(O)CN1C(=O)C2(COc3cc4c(cc32)OCO4)c2ccccc21
Temperature: 0 °C
Reaction time: 17 h
Yield: 102 %

Procedure:
To a suspension of ethyl(2′-oxospiro[furo[2,3-f][1,3]benzodioxole-7,3′-indol]-1′(2′H)-yl)acetate (10.5 g, 24.5 mmol) in THF (200 mL) and water (100 mL) was added lithium hydroxide monohydrate (3.98 g, 95.0 mmol) at 0° C. The reaction mixture was stirred at 0° C. for 30 min and at ambient temperature for 17 h. The mixture was neutralized with of 4 M HCl (15.0 mL). The residue obtained upon removing the solvent was acidified by the addition of 4 M HCl (6.2 mL) to pH 3. The solid was filtered, washed with water and hexane, and dried under the reduced pressure to give the title compound (8.48 g, 87%) as a white solid: 1H NMR (300 MHz, CDCl3) δ 7.32-7.06 (m, 4H), 6.79 (d, 1H), 6.49 (s, 1H), 6.23 (s, 1H), 5.84 (m, 2H), 4.92 (m, 1H), 4.69-4.63 (m, 2H), 4.45 (m, 1H); 13C NMR (75 MHz, CDCl3) δ 177.8, 171.8, 155.8, 149.0, 142.4, 141.2, 132.0, 129.0, 124.1, 124.0, 119.2, 108.3, 103.4, 101.5, 93.5, 80.2, 58.2, 41.1; MS (ES−) m/z 338.2 (M−1).
Reaction SMILES: [CH:1]1([C:6]2([CH2:14][CH2:15][C:16]3[CH:21]=[CH:20][C:19]([CH2:22][C:23]#[N:24])=[C:18]([CH2:25][CH3:26])[CH:17]=3)[CH2:11][C:10](=[O:12])[CH2:9][C:8](=[O:13])[O:7]2)[CH2:5][CH2:4][CH2:3][CH2:2]1.[CH3:27][C:28]1[CH:33]=[C:32]([CH3:34])[N:31]2[N:35]=[C:36]([CH:38]=O)[N:37]=[C:30]2[N:29]=1>CO>[CH:1]1([C:6]2([CH2:14][CH2:15][C:16]3[CH:21]=[CH:20][C:19]([CH2:22][C:23]#[N:24])=[C:18]([CH2:25][CH3:26])[CH:17]=3)[CH2:11][C:10]([OH:12])=[C:9]([CH2:38][C:36]3[N:37]=[C:30]4[N:29]=[C:28]([CH3:27])[CH:33]=[C:32]([CH3:34])[N:31]4[N:35]=3)[C:8](=[O:13])[O:7]2)[CH2:5][CH2:4][CH2:3][CH2:2]1
Reactant: CCc1cc(CCC2(C3CCCC3)CC(=O)CC(=O)O2)ccc1CC#N
Reactant: Cc1cc(C)n2nc(C=O)nc2n1
Solvent: CO
Product: CCc1cc(CCC2(C3CCCC3)CC(O)=C(Cc3nc4nc(C)cc(C)n4n3)C(=O)O2)ccc1CC#N
Reaction time: 0.08 h
Yield: 20.5 %

Procedure:
To a solution of {4-[2-(2-cyclopentyl-4,6-dioxotetrahydro-2H-pyran-2-yl)ethyl]-2-ethylphenyl}acetonitrile (200 mg, 0.57 mmol, example A(102)) in anhydrous MeOH (6 mL) at room temperature was added 5,7-dimethyl[1,2,4]triazolo[1,5-a]pyrimidine-2-carbaldehyde (120 mg, 0.68 mmol). The mixture was stirred for 5 min before borane-dimethylamine complex (37 mg, 0.62 mmol) was added. The reaction was stirred at that temperature for 15 hours before it was quenched by the addition of 1.0 N HCl. The solvent was removed and the residue was purified by HPLC to obtain the desired product (60 mg, 21% yield). 1H NMR (300 MHz, DMSO-d6): δ 1.03 (t, J=7.5 Hz, 3 H), 1.32–1.64 (m, 8 H), 2.06 (m, 2 H), 2.36–2.55 (m, 12 H), 2.73 (d, J=17.9 Hz, 1 H), 3.64 (d, J=16.1 Hz, 1 H), 3.77 (d, J=16.4 Hz, 1 H), 3.89 (s, 2 H), 6.95 (s, 1 H), 7.00 (s, 1 H), 7.04 (d, J=7.7 Hz, 1 H), 7.17 (d, J=7.7 Hz, 1 H), 10.81 (s, 1 H).
Reaction SMILES: [CH3:1][C:2]1[CH:3]=[C:4]([O:15][C:16]2[C:25]3[C:20](=[CH:21][C:22]([OH:28])=[C:23]([O:26][CH3:27])[CH:24]=3)[N:19]=[CH:18][CH:17]=2)[C:5]([C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)=[N:6][C:7]=1[CH3:8].C(=O)([O-])[O-].[K+].[K+].Br[CH2:36][CH2:37][OH:38]>CN(C)C=O>[CH3:1][C:2]1[CH:3]=[C:4]([O:15][C:16]2[C:25]3[C:20](=[CH:21][C:22]([O:28][CH2:36][CH2:37][OH:38])=[C:23]([O:26][CH3:27])[CH:24]=3)[N:19]=[CH:18][CH:17]=2)[C:5]([C:9]2[CH:10]=[CH:11][CH:12]=[CH:13][CH:14]=2)=[N:6][C:7]=1[CH3:8]
Reactant: COc1cc2c(Oc3cc(C)c(C)nc3-c3ccccc3)ccnc2cc1O
Reactant: OCCBr
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: COc1cc2c(Oc3cc(C)c(C)nc3-c3ccccc3)ccnc2cc1OCCO
Temperature: 70 °C
Reaction time: 8 h
Yield: 76 %

Procedure:
4-(5,6-Dimethyl-2-phenyl-pyridin-3-yloxy)-6-methoxy-quinolin-7-ol (compound 332) (162 mg) was dissolved in N,N-dimethylformamide (3 ml) to prepare a solution. Potassium carbonate (180 mg) and 2-bromoethanol (0.1 ml) were added to the solution, and the mixture was stirred at 70° C. overnight. The solvent was removed by distillation under the reduced pressure, water was then added to the residue, and the mixture was extracted with chloroform. The chloroform layer was washed with saturated brine and was dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure, and the residue was purified by thin layer chromatography using chloroform-acetone to give the title compound (135 mg, yield 76%).
Reaction SMILES: [C:1]12([NH:11][C:12]3[N:17]=[C:16]([NH:18][C:19]45[CH2:28][CH:23]6[CH2:24][CH:25]([CH2:27][CH:21]([CH2:22]6)[CH2:20]4)[CH2:26]5)[CH:15]=[C:14](Cl)[N:13]=3)[CH2:10][CH:5]3[CH2:6][CH:7]([CH2:9][CH:3]([CH2:4]3)[CH2:2]1)[CH2:8]2.[NH:30]1[CH2:35][CH2:34][NH:33][CH2:32][CH2:31]1>>[C:1]12([NH:11][C:12]3[N:17]=[C:16]([NH:18][C:19]45[CH2:28][CH:23]6[CH2:24][CH:25]([CH2:27][CH:21]([CH2:22]6)[CH2:20]4)[CH2:26]5)[CH:15]=[C:14]([N:30]4[CH2:35][CH2:34][NH:33][CH2:32][CH2:31]4)[N:13]=3)[CH2:10][CH:5]3[CH2:6][CH:7]([CH2:9][CH:3]([CH2:4]3)[CH2:2]1)[CH2:8]2
Reactant: Clc1cc(NC23CC4CC(CC(C4)C2)C3)nc(NC23CC4CC(CC(C4)C2)C3)n1
Reactant: C1CNCCN1
Product: c1c(NC23CC4CC(CC(C4)C2)C3)nc(NC23CC4CC(CC(C4)C2)C3)nc1N1CCNCC1
Yield: 83.36 %

Procedure:
2,4-bis(1-adamantylamino)-6-chloropyrimidine is reacted with piperazine as described in Example 17 to give the title compound in a yield of 83.36%, m.p. 168°-175° C.
Reaction SMILES: [F:1][C:2]1[C:10]([F:11])=[C:9]([F:12])[C:8]([F:13])=[C:7]([F:14])[C:3]=1[CH:4]1[O:6][CH2:5]1.[CH3:15][Al](C)C.Cl>ClCCl.CCCCCC>[F:1][C:2]1[C:3]([CH:4]([CH3:15])[CH2:5][OH:6])=[C:7]([F:14])[C:8]([F:13])=[C:9]([F:12])[C:10]=1[F:11]
Reactant: C[Al](C)C
Reactant: Fc1c(F)c(F)c(C2CO2)c(F)c1F
Agent: Cl
Solvent: CCCCCC
Solvent: ClCCl
Product: CC(CO)c1c(F)c(F)c(F)c(F)c1F

Procedure:
A solution of 10.5 g of (+)-2,3,4,5,6-pentafluorostyrene oxide (over 95%ee) in 50 ml of dichloromethane was added dropwise to 100 ml of a 1.0M solution of trimethylaluminum in hexane, and was reacted for 40 hours at room temperature. This reaction mixture was poured into 100 ml of 1N hydrochloric acid. After the aqueous layer was extracted with ether, the total organic solution was dried over magnesium sulfate. The solvent was distilled out under reduced pressure, and the subsequent distillation under reduced pressure gave 10.6 g of (+)-2-(pentafluorophenyl)-1-propanol having the aforementioned physical properties.
Reaction SMILES: I[C:2]1[CH:3]=[C:4]([CH:14]=[CH:15][CH:16]=1)[O:5][CH2:6][C:7]([O:9][C:10]([CH3:13])([CH3:12])[CH3:11])=[O:8].[CH2:17]([OH:20])[C:18]#[CH:19].C(OCC)(=O)C>C(N(CC)CC)C.[Cu]I.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[OH:20][CH2:17][C:18]#[C:19][C:2]1[CH:3]=[C:4]([CH:14]=[CH:15][CH:16]=1)[O:5][CH2:6][C:7]([O:9][C:10]([CH3:13])([CH3:12])[CH3:11])=[O:8]
Reactant: C#CCO
Reactant: CC(C)(C)OC(=O)COc1cccc(I)c1
Agent: Cl[Pd](Cl)([P](c1ccccc1)(c1ccccc1)c1ccccc1)[P](c1ccccc1)(c1ccccc1)c1ccccc1
Agent: [Cu]I
Solvent: CCN(CC)CC
Solvent: CCOC(C)=O
Product: CC(C)(C)OC(=O)COc1cccc(C#CCO)c1
Temperature: 70 °C
Reaction time: 1 h
Yield: 68.2 %

Procedure:
The compound (1.00 g, 3.00 mmol) of Example 22-1 was dissolved in triethylamine (30 ml) under an atmosphere of nitrogen. Thereto were added propargyl alcohol (0.35 ml, 6.00 mmol), copper(I) iodide (6.00 mg, 30.0 μmol) and dichlorobis(triphenylphosphine)palladium (II) (42.0 mg, 60.0 μmol) and the mixture was stirred for 1 hour at 70° C. The mixture was cooled and thereto was added ethyl acetate. The mixture was washed with 10% aqueous citric acid solution, water, an aqueous saturated sodium hydrogencarbonate solution and an aqueous saturated sodium chloride solution in the order and dried over sodium sulfate. The solvent was removed and purified with silica gel chromatography (hexane:ethyl acetate, 3:1–2:1) to give the subject compound as a yellow oil(537 mg, 68%).
Reaction SMILES: O[CH:2]1[C:8]2[CH:9]=[CH:10][CH:11]=[CH:12][C:7]=2[CH2:6][O:5][C:4]2[CH:13]=[CH:14][C:15]([C:17]([O:19][CH3:20])=[O:18])=[CH:16][C:3]1=2.[S:21]([Cl:24])([Cl:23])=[O:22]>C1C=CC=CC=1>[S:21]([Cl:24])([Cl:23])=[O:22].[Cl:23][CH:2]1[C:8]2[CH:9]=[CH:10][CH:11]=[CH:12][C:7]=2[CH2:6][O:5][C:4]2[CH:13]=[CH:14][C:15]([C:17]([O:19][CH3:20])=[O:18])=[CH:16][C:3]1=2
Reactant: COC(=O)c1ccc2c(c1)C(O)c1ccccc1CO2
Solvent: O=S(Cl)Cl
Solvent: c1ccccc1
Product: COC(=O)c1ccc2c(c1)C(Cl)c1ccccc1CO2
Yield: 100 %

Procedure:
Reflux 3.14 gm. of methyl 6,11-dihydro-11-hydroxydibenz[b,e]oxepin-2-carboxylate and 15 cc. of thionyl chloride for 10 minutes. Evaporate excess thionylchloride. Remove traces of thionyl chloride by co-distillation with benzene to obtain the title product (yield 3.35 gm., 100%).
Reaction SMILES: [CH3:1][C:2](=[O:5])[CH2:3][CH3:4].[CH:6]12[CH2:12][CH:9]([CH:10]=[CH:11]1)[CH2:8][CH:7]2[CH:13]=O.[OH-].[Na+].C1(C)C(S(O)(=O)=O)=CC=CC=1>O>[CH:9]12[CH2:12][CH:6]([CH:7]([CH:13]=[C:3]([CH3:4])[C:2](=[O:5])[CH3:1])[CH2:8]1)[CH:11]=[CH:10]2
Reactant: O=CC1CC2C=CC1C2
Reactant: CCC(C)=O
Agent: Cc1ccccc1S(=O)(=O)O
Agent: [Na+]
Agent: [OH-]
Solvent: O
Product: CC(=O)C(C)=CC1CC2C=CC1C2
Temperature: 70 °C
Reaction time: 0.5 h

Procedure:
A mixture of 80 ml. of 2-butanone (1.1 moles), 61.1 grams (0.5 moles) of 5-norbornene-2-carboxaldehyde, and 250 ml. of water containing 6 ml. of 40% sodium hydroxide solution was stirred rapidly at 50°C. for 2 hours when most of the aldehyde had been consumed (as determined by infrared analysis) and an aldol had formed. Stirring was continued and the temperature was slowly raised to 70°C. and kept there for 30 minutes causing dehydration of 75% of the aldol. A small amount of toluene sulfonic acid was added which catalyzed the dehydration of the remaining aldol. 90.8 grams of crude material which was a viscous liquid was distilled through a short Vigreux-column to give 4-(5-norbornenyl)-3-methyl-but-3-en-2-one which had a boiling point of 121°-122°C. at 10 mm., nD 25 = 1.5156.
Reaction SMILES: C(OC(=O)[NH:7][C@H:8]([CH2:13][N:14]([C:26]([C@H:28]1[CH2:30][C@@H:29]1[C:31]1[CH:36]=[CH:35][CH:34]=[C:33]([F:37])[N:32]=1)=[O:27])[C:15]1[CH:20]=[CH:19][C:18]([C:21]#[C:22][CH2:23][CH2:24][CH3:25])=[CH:17][CH:16]=1)[C@@H:9]([CH3:12])[CH2:10][CH3:11])(C)(C)C.FC(F)(F)C(O)=O>ClCCl>[NH2:7][C@@H:8]([C@@H:9]([CH3:12])[CH2:10][CH3:11])[CH2:13][N:14]([C:15]1[CH:20]=[CH:19][C:18]([C:21]#[C:22][CH2:23][CH2:24][CH3:25])=[CH:17][CH:16]=1)[C:26]([C@H:28]1[CH2:30][C@@H:29]1[C:31]1[CH:36]=[CH:35][CH:34]=[C:33]([F:37])[N:32]=1)=[O:27]
Reactant: CCCC#Cc1ccc(N(C[C@@H](NC(=O)OC(C)(C)C)[C@@H](C)CC)C(=O)[C@H]2C[C@@H]2c2cccc(F)n2)cc1
Solvent: O=C(O)C(F)(F)F
Solvent: ClCCl
Product: CCCC#Cc1ccc(N(C[C@@H](N)[C@@H](C)CC)C(=O)[C@H]2C[C@@H]2c2cccc(F)n2)cc1
Temperature: 25 °C
Reaction time: 1 h
Yield: 52.2 %

Procedure:
((1S,2S)-1-{[[(1S,2S)-2-(6-Fluoro-pyridin-2-yl)-cyclopropanecarbonyl]-(4-pent-1-ynyl-phenyl)-amino]-methyl}-2-methyl-butyl)-carbamic acid t-butyl ester (0.0657 g, 0.126 mmol), trifluoroacetic acid (1 mL) and dichloromethane (2 mL) were mixed at 0° C., then stirred at room temperature for 1 hr. The excessive solvent was removed in vacuum. The residue was purified by preparatory HPLC to give a white solid (0.0277 g, 34%): 1H NMR (400 MHz, MeOD) δ ppm 7.66 (m, 1H), 7.24 (m, 4H), 7.07 (td, J=7.1, 2.3 Hz, 1H), 6.66 (m, 1H), 4.16 (m, 1H), 3.58 (m, 1H), 3.21 (dt, J=3.3, 1.6 Hz, 1H), 2.47 (br. s., 1H), 2.29 (td, J=7.0, 3.2 Hz, 2H), 1.81 (dd, J=5.3, 3.5 Hz, 1H), 1.62 (m, 1H), 1.53 (m, 3H), 1.29 (m, 2H), 1.10 (m, 1H), 0.95 (td, J=7.3, 2.5 Hz, 3H), 0.86 (dd, J=7.1, 4.8 Hz, 3H), 0.73 (m, 3H); LCMS (ESI) m/e 422.3 [(M+H)+, calcd for C26H33FN3O 422.6].
Reaction SMILES: Cl[CH2:2][CH2:3][CH2:4][C:5]([C:7]1[CH:12]=[CH:11][C:10]([CH3:13])=[C:9]([CH3:14])[CH:8]=1)=[O:6].[CH3:15][CH:16]([CH3:32])[C:17]([NH:19][C:20]1[CH:25]=[CH:24][CH:23]=[C:22]([CH:26]2[CH2:31][CH2:30][NH:29][CH2:28][CH2:27]2)[N:21]=1)=[O:18]>>[CH3:14][C:9]1[CH:8]=[C:7]([C:5](=[O:6])[CH2:4][CH2:3][CH2:2][N:29]2[CH2:30][CH2:31][CH:26]([C:22]3[N:21]=[C:20]([NH:19][C:17](=[O:18])[CH:16]([CH3:15])[CH3:32])[CH:25]=[CH:24][CH:23]=3)[CH2:27][CH2:28]2)[CH:12]=[CH:11][C:10]=1[CH3:13]
Reactant: CC(C)C(=O)Nc1cccc(C2CCNCC2)n1
Reactant: Cc1ccc(C(=O)CCCCl)cc1C
Product: Cc1ccc(C(=O)CCCN2CCC(c3cccc(NC(=O)C(C)C)n3)CC2)cc1C

Procedure:
Prepared by Procedure G and Scheme AI using 4-chloro-1-(3,4-dimethylphenyl)-1-butanone and 2-methyl-N-[6-(4-piperidinyl)-2-pyridinyl]propanamide: ESMS m/e: 422.1 (M+H)+.
Reaction SMILES: [CH3:1][O:2][C:3]1[C:4]([NH2:9])=[CH:5][CH:6]=[CH:7][CH:8]=1.[CH2:10]=[CH:11][C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1>C(OCC)(=O)C.CCCCCC>[C:12]1([CH2:11][CH2:10][NH:9][C:4]2[CH:5]=[CH:6][CH:7]=[CH:8][C:3]=2[O:2][CH3:1])[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1
Reactant: C=Cc1ccccc1
Reactant: COc1ccccc1N
Solvent: CCOC(C)=O
Solvent: CCCCCC
Product: COc1ccccc1NCCc1ccccc1
Yield: 85 %

Procedure:
According to GWM, 0.011 mol (=1.25 ml) of o-anisidine and 0.011 mol (=1.25 ml) of styrene are reacted with one another. The product is isolated by column chromatography using ethyl acetate/n-hexane (1:5) as eluent, the product N-(2-phenylethyl)-(o-methoxy)aniline being obtained as a slightly pink liquid.
Reaction SMILES: [N:1]1([CH2:7][CH2:8][NH:9][C:10]([C:12]2[NH:13][C:14]([CH:18]=[C:19]3[C:27]4[C:22](=[N:23][CH:24]=[CH:25][C:26]=4Cl)[NH:21][C:20]3=[O:29])=[C:15]([CH3:17])[CH:16]=2)=[O:11])[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1.[Cl:30][C:31]1[CH:32]=[C:33]([NH2:38])[CH:34]=[CH:35][C:36]=1[F:37].O.C1(C)C=CC(S(O)(=O)=O)=CC=1>COCCOCCOC>[N:1]1([CH2:7][CH2:8][NH:9][C:10]([C:12]2[NH:13][C:14]([CH:18]=[C:19]3[C:27]4[C:22](=[N:23][CH:24]=[CH:25][C:26]=4[NH:38][C:33]4[CH:34]=[CH:35][C:36]([F:37])=[C:31]([Cl:30])[CH:32]=4)[NH:21][C:20]3=[O:29])=[C:15]([CH3:17])[CH:16]=2)=[O:11])[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1
Reactant: Cc1cc(C(=O)NCCN2CCOCC2)[nH]c1C=C1C(=O)Nc2nccc(Cl)c21
Reactant: Nc1ccc(F)c(Cl)c1
Agent: Cc1ccc(S(=O)(=O)O)cc1
Solvent: COCCOCCOC
Solvent: O
Product: Cc1cc(C(=O)NCCN2CCOCC2)[nH]c1C=C1C(=O)Nc2nccc(Nc3ccc(F)c(Cl)c3)c21
Temperature: 185 °C
Yield: 28 %

Procedure:
A mixture of 5-(4-chloro-2-oxo-1,2-dihydro-pyrrolo[2,3-b]pyridin-3-ylidenemethyl)-4-methyl-1H-pyrrole-2-carboxylic acid (2-morpholin-4-yl-ethyl)-amide (10 mg, 0.024 mmol), 3-chloro-4-fluoro-phenylamine (50 mg, 0.34 mmol), p-toluene sulfonic acid monohydrate (5 mg, 0.026 mmol) and 1 mL of 2-methoxyethyl ether was heated to 180-190° C. in a sealed tube for 6 hours, cooled to room temperature and concentrated. The residue was then purified using preparative TLC plates eluting with 10% methanol in dichloromethane to give 5-[4-(3-chloro-4-fluoro-phenylamino)-2-oxo-1,2-dihydro-pyrrolo[2,3-b]pyridin-3-ylidenemethyl]-4-methyl-1H-pyrrole-2-carboxylic acid (2-morpholin-4-yl-ethyl)-amide as an orange solid (yield is about 28%).
Reaction SMILES: [CH3:1][C:2]1([CH3:26])[O:6][C@H:5]([CH2:7][O:8][C:9]2[CH:14]=[CH:13][C:12]([CH2:15][CH2:16][CH2:17]/[CH:18]=[N:19]/[S:20]([C:22]([CH3:25])([CH3:24])[CH3:23])=[O:21])=[CH:11][CH:10]=2)[CH2:4][O:3]1.[CH:27]([Mg]Br)=[CH2:28]>C1COCC1>[CH3:1][C:2]1([CH3:26])[O:6][C@H:5]([CH2:7][O:8][C:9]2[CH:10]=[CH:11][C:12]([CH2:15][CH2:16][CH2:17][CH:18]([NH:19][S:20]([C:22]([CH3:25])([CH3:24])[CH3:23])=[O:21])[CH:27]=[CH2:28])=[CH:13][CH:14]=2)[CH2:4][O:3]1
Reactant: C=C[Mg]Br
Reactant: CC1(C)OC[C@@H](COc2ccc(CCC/C=N/S(=O)C(C)(C)C)cc2)O1
Solvent: C1CCOC1
Product: C=CC(CCCc1ccc(OC[C@@H]2COC(C)(C)O2)cc1)NS(=O)C(C)(C)C
Temperature: 0 °C
Reaction time: 0.5 h

Procedure:
To a solution of 2-Methyl-propane-2-sulfinic acid [4-[4-((R)-2,2-dimethyl-[1,3]dioxolan-4-ylmethoxy)-phenyl]-but-(E)-ylidene]-amide (4.51 g, 11.8 mmol) in THF (120 ml) at 0° C. is added vinylmagnesium bromide (11.8 ml of a 1 M solution in THF, 11.8 mmol) dropwise. After addition is complete, the mixture is stirred at 0° C. for 30 minutes then quenched with sat. aq. NH4Cl solution (20 ml). This mixture is allowed to warm to room temperature and diluted with water (50 ml) and EtOAc (50 ml). The organic phase is separated, dried (MgSO4) and concentrated in vacuo. Purification by chromatography (SiO2, EtOAc/iso-hexane) affords 2-Methyl-propane-2-sulfinic acid {4-[4-((R)-2,2-dimethyl-[1,3]dioxolan-4-ylmethoxy)-phenyl]-1-vinyl-butyl}-amide as a mixture of diastereomers as a gum; [M+H]+ 410.39
Reaction SMILES: [CH3:1][OH:2].[H-].[Na+].[Cl:5][C:6]1[CH:7]=[C:8]2[C:16](=[C:17]([N+:20]([O-:22])=[O:21])[C:18]=1F)[NH:15][C:14]1[CH:13]=[N:12][CH:11]=[CH:10][C:9]2=1.O>CN(C=O)C>[Cl:5][C:6]1[CH:7]=[C:8]2[C:16](=[C:17]([N+:20]([O-:22])=[O:21])[C:18]=1[O:2][CH3:1])[NH:15][C:14]1[CH:13]=[N:12][CH:11]=[CH:10][C:9]2=1
Reactant: O=[N+]([O-])c1c(F)c(Cl)cc2c1[nH]c1cnccc12
Reactant: CO
Agent: [H-]
Agent: [Na+]
Solvent: O
Solvent: CN(C)C=O
Product: COc1c(Cl)cc2c([nH]c3cnccc32)c1[N+](=O)[O-]
Temperature: 25 °C
Reaction time: 0.33 h
Yield: 96.7 %

Procedure:
Methanol (0.462 ml, 11.4 mmol) was added to a stirring suspension of NaH (684 mg, 17.1 mmol) in DMF (10 ml) under an argon atmosphere. The resulting solution was allowed to stir at RT for 20 min. 6-chloro-7-fluoro-8-nitro-9H-β-carboline (500 mg, 1.9 mmol) was added to the stirring solution and the resulting mixture was allowed to stir at RT. Upon addition of H2O, a brown solid precipitated out which was filtered to give the desired 6-chloro-7-methoxy-8-nitro-9H-β-carboline (510 mg, 97% yield). 1H-NMR (300 MHz, DMSO-d6): δ 4.02 (s, 3H), 8.52 (d, 1H), 8.60 (d, 1H), 9.05 (s, 1H), 9.12 (s, 1H), 12.78 (b, 1H). Retention Time (LC, method: ammonium acetate standard): 2.28 min. MS (M+H+): 278.
Reaction SMILES: [CH3:1][N:2]1[C:6]([C:7]([F:10])([F:9])[F:8])=[CH:5][C:4](OS(C2C=CC(C)=CC=2)(=O)=O)=[N:3]1.[C:22]([C:24]1[CH2:29][CH2:28][CH2:27][CH2:26][CH:25]=1)#[CH:23]>CCCCCCC.C(Cl)Cl>[C:24]1([C:22]#[C:23][C:4]2[CH:5]=[C:6]([C:7]([F:8])([F:9])[F:10])[N:2]([CH3:1])[N:3]=2)[CH2:29][CH2:28][CH2:27][CH2:26][CH:25]=1
Reactant: Cc1ccc(S(=O)(=O)Oc2cc(C(F)(F)F)n(C)n2)cc1
Reactant: C#CC1=CCCCC1
Solvent: CCCCCCC
Solvent: ClCCl
Product: Cn1nc(C#CC2=CCCCC2)cc1C(F)(F)F

Procedure:
This product was prepared from toluene-4-sulfonic acid 1-methyl-5-trifluoromethyl-1H-pyrazol-3-yl ester and 1-ethynyl-cyclohexene following the general procedure for the Sonogashira cross-coupling reaction described above. Chromatography eluent: heptane/DCM 7:3; yield (80 mg, 63%); 1H NMR δ (CDCl3): 6.63 (s, 1H), 6.27-6.29 (m, 1H), 3.96 (s, 3H), 2.14-2.22 (m, 4H), 1.73-1.58 (m, 4H); LCMS m/z: 254.
Reaction SMILES: [N+:1]([C:4]1[CH:9]=[CH:8][C:7]([N:10]2[CH2:15][CH2:14][NH:13][CH2:12][CH2:11]2)=[CH:6][CH:5]=1)([O-:3])=[O:2].[N+:16]([C:19]1[CH:27]=[CH:26][C:22]([CH2:23][CH2:24]Br)=[CH:21][CH:20]=1)([O-:18])=[O:17].C(=O)(O)[O-].[Na+]>C(#N)C>[N+:1]([C:4]1[CH:5]=[CH:6][C:7]([N:10]2[CH2:15][CH2:14][N:13]([CH2:24][CH2:23][C:22]3[CH:21]=[CH:20][C:19]([N+:16]([O-:18])=[O:17])=[CH:27][CH:26]=3)[CH2:12][CH2:11]2)=[CH:8][CH:9]=1)([O-:3])=[O:2]
Reactant: O=[N+]([O-])c1ccc(CCBr)cc1
Reactant: O=[N+]([O-])c1ccc(N2CCNCC2)cc1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CC#N
Product: O=[N+]([O-])c1ccc(CCN2CCN(c3ccc([N+](=O)[O-])cc3)CC2)cc1
Yield: 50.8 %

Procedure:
1-(4-Nitrophenyl)piperazine (4.14 g), 4-nitrophenethyl bromide (4.6 g) and sodium bicarbonate (3.4 g) in acetonitrile (75 ml) were stirred under reflux for 1 day, and then evaporated to dryness. The residue was then triturated with water (300 ml), filtered, washed with water (300 ml), and the resulting solid was crystallized from ethyl acetate, yielding the title compound, (3.62 g), m.p. 143°-5°.