Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[C:6]([NH2:8])[CH:5]=[CH:4][C:3]=1[CH2:9][CH2:10][C:11]([O:13]CC)=O>CCO>[NH2:8][C:6]1[CH:7]=[C:2]2[C:3]([CH2:9][CH2:10][C:11](=[O:13])[NH:1]2)=[CH:4][CH:5]=1
Reactant: CCOC(=O)CCc1ccc(N)cc1N
Solvent: CCO
Product: Nc1ccc2c(c1)NC(=O)CC2
Temperature: 25 °C
Yield: 86.6 %

Procedure:
A suspension of Pd(OH)2/C (10%, 3.0 g) and (E)-ethyl 3-(2,4-dinitrophenyl)acrylate (12.0 g, 45.1 mmol) in MeOH (80 mL) was stirred at 25° C. under an atmosphere of H2 (45 psi) for 15 h. The mixture was filtered and the filtrate was concentrated in vacuo to give 3-(2,4-diamino-phenyl)-propionic acid ethyl ester (8.6 g, 98%), which was used directly in the next step without further purification. A solution of ethyl 3-(2,4-diaminophenyl)propanoate (8.6 g, 41.3 mmol) in EtOH (50 mL) was stirred at 85-100° C. for 48 h. The reaction mixture was cooled to ambient temperature and the solvent was removed in vacuo. EtOAc (10 mL) was added to the residue and the precipitate was collected by filtration to give 7-amino-3,4-dihydro-1H-quinolin-2-one (5.8 g, 87%). 1H NMR (DMSO-d6, 400 MHz): δ 9.83 (brs, 1H), 6.76 (d, J=7.6 Hz, 1H), 6.12 (m, 2H), 4.95 (brs, 2H), 2.65 (t, J=7.2 Hz, 2H), 2.36 (t, J=7.2 Hz, 2H).
Reaction SMILES: C(OC([N:8]1[CH2:17][CH2:16][C:15]2[C:11](=[C:12](OS(C(F)(F)F)(=O)=O)[N:13]([CH:18]3[CH2:22][CH2:21][CH2:20][CH2:19]3)[N:14]=2)[CH2:10][CH2:9]1)=O)(C)(C)C.[S:31]1[CH:35]=[CH:34][CH:33]=[C:32]1B(O)O>>[CH:18]1([N:13]2[C:12]([C:32]3[S:31][CH:35]=[CH:34][CH:33]=3)=[C:11]3[C:15]([CH2:16][CH2:17][NH:8][CH2:9][CH2:10]3)=[N:14]2)[CH2:19][CH2:20][CH2:21][CH2:22]1
Reactant: OB(O)c1cccs1
Reactant: CC(C)(C)OC(=O)N1CCc2nn(C3CCCC3)c(OS(=O)(=O)C(F)(F)F)c2CC1
Product: c1csc(-c2c3c(nn2C2CCCC2)CCNCC3)c1
Yield: 65.5 %

Procedure:
The title compound (83 mg) was prepared according to Example 180 using 200 mg of 2-cyclopentyl-3-trifluoromethanesulfonyloxy-4,5,7,8-tetrahydro-2H-1,2,6-triaza-azulene-6-carboxylic acid tert-butyl ester (Example 180, Step A) and 282 mg of 2-thiopheneboronic acid. MS (ESI): exact mass calculated for C16H21N3S, 287.15. found, m/z 288.4 [M+H]+. 1H NMR (500 MHz, CD3OD): 7.70-7.68 (m, 1H), 7.24-7.22 (m, 1H), 7.15-7.14 (m, 1H), 4.64 (m, 1H), 3.41-3.39 (m, 2H), 3.16-3.15 (m, 2H), 2.85-2.83 (m, 2H), 2.01-1.88 (m, 6H), 1.64-1.60 (m, 2H).
Reaction SMILES: C(=O)([O-])[O-].[K+].[K+].[CH3:7][CH:8]([SH:10])[CH3:9].Cl[C:12]1[N:16]([CH3:17])[N:15]=[C:14]([C:18]([F:21])([F:20])[F:19])[C:13]=1[CH:22]=[O:23]>CN(C=O)C>[CH:8]([S:10][C:12]1[N:16]([CH3:17])[N:15]=[C:14]([C:18]([F:20])([F:19])[F:21])[C:13]=1[CH:22]=[O:23])([CH3:9])[CH3:7]
Reactant: CC(C)S
Reactant: Cn1nc(C(F)(F)F)c(C=O)c1Cl
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: CC(C)Sc1c(C=O)c(C(F)(F)F)nn1C
Temperature: 25 °C
Reaction time: 16 h
Yield: 102.4 %

Procedure:
Potassium carbonate (1.68 g, 12 mmol) was suspended in DMF (50 ml) and isopropylthiol (1 ml, 11 mmol) added. The suspension was stirred at room temperature for 15 minutes before a solution of 5-chloro-1-methyl-3-trifluoromethyl-1H-pyrazole-4-carbaldehyde (2.12 g, 10 mmol) in DMF (5 ml) was added. The reaction was stirred at room temperature for 16 hours. The reaction was partitioned between aqueous ammonium chloride solution and diethyl ether and the two phases were separated. The organic phase was washed with water and brine, dried over sodium sulfate and concentrated to give the product (2.584 g, 100% yield) which was used without further purification. 1H NMR (400 MHz, CDCl3): 1.29 (3H, s, Me), 1.31 (3H, s, Me), 3.52 (1H, heptet, CH), 4.02 (3H, s, Me), 10.03 (1H, s, CH).
Reaction SMILES: [CH3:1][O:2][CH2:3][O:4][C:5]1[C:6](B(O)O)=[CH:7][C:8]([CH3:11])=[N:9][CH:10]=1.OO.S(OOS([O-])(=O)=O)([O-])(=O)=[O:18].[Na+].[Na+]>O1CCCC1>[CH3:1][O:2][CH2:3][O:4][C:5]1[C:6](=[O:18])[CH:7]=[C:8]([CH3:11])[NH:9][CH:10]=1
Reactant: COCOc1cnc(C)cc1B(O)O
Reactant: O=S(=O)([O-])OOS(=O)(=O)[O-]
Agent: OO
Agent: [Na+]
Solvent: C1CCOC1
Product: COCOc1c[nH]c(C)cc1=O
Temperature: 25 °C
Reaction time: 4 h
Yield: 100 %

Procedure:
To a solution of 5-(methoxymethoxy)-2-methylpyridin-4-ylboronic acid (500 mg, 2.54 mmol) in tetrahydrofuran (12.7 mL), an aqueous solution of hydrogen peroxide (purity 30%) (2.9 mL, 25.4 mmol) was added at room temperature, and the mixture was stirred at room temperature for 4 hours. The reaction solution was added a saturated aqueous solution of sodium persulfate, and concentrated in vacuo. The obtained residue was washed and filtered with chloroform/methanol, and the title compound (440 mg (yield >100%)) was obtained as a yellow amorphous.
Reaction SMILES: Cl[C:2]1[C:3]2[N:4]([C:13]([CH3:16])=[CH:14][N:15]=2)[C:5]2[C:10]([N:11]=1)=[CH:9][CH:8]=[C:7]([Cl:12])[CH:6]=2.[CH:17]1([NH2:22])[CH2:21][CH2:20][CH2:19][CH2:18]1>>[CH:17]1([NH:22][C:2]2[C:3]3[N:4]([C:13]([CH3:16])=[CH:14][N:15]=3)[C:5]3[C:10]([N:11]=2)=[CH:9][CH:8]=[C:7]([Cl:12])[CH:6]=3)[CH2:21][CH2:20][CH2:19][CH2:18]1
Reactant: NC1CCCC1
Reactant: Cc1cnc2c(Cl)nc3ccc(Cl)cc3n12
Product: Cc1cnc2c(NC3CCCC3)nc3ccc(Cl)cc3n12

Procedure:
By reaction of 2,3,6-trichloroquinoxaline with propargylamine, following a procedure that is similar to that described in example 2, there is obtained 8-chloro-1-methylimidazo[1,2-a]quinoxaline-4(5H)-one (m.p. >300° C.) and, subsequently, 4,8-dichloro-1-methylimidazo[1,2-a] quinoxaline. By reacting this product with cyclopentylamine according to the method described in example 3, there is obtained 4-cyclopentylamino-8chloro-1-methylimidazo[1,2-a]quinoxaline. m.p. (DSC)=130.5° C.(onset); IR (KBr): 3421, 2954, 1555 cm-1 ; 1H-NMR (CDCl3): δ7.95 (1H,d, J=2 Hz), 7.6 (1H,d, J=9 Hz), 7.35÷7.15 (2H,m), 6.1 (1H,d), 4.5 (1H,s), 2.8 (3H,s), 2.4÷2.05 (4H,m), 2.0÷1.3 (4H,m); UV (EtOH): λmax =227, 251, 276, 305, 336 nm. Elementary analysis for C16H17ClN4 (m.w. 300.79): calcd. C 63.89, H 5.70, N 18.63%; found C 63.79, H 5.79, N 18.58%.
Reaction SMILES: Br[CH2:2][CH2:3][CH2:4][CH2:5][C:6]([CH2:14][CH3:15])([CH2:12][CH3:13])[C:7]([O:9][CH2:10][CH3:11])=[O:8].[S-:16][C:17]#[N:18].[K+]>>[CH2:12]([C:6]([CH2:14][CH3:15])([CH2:5][CH2:4][CH2:3][CH2:2][S:16][C:17]#[N:18])[C:7]([O:9][CH2:10][CH3:11])=[O:8])[CH3:13]
Reactant: N#C[S-]
Reactant: CCOC(=O)C(CC)(CC)CCCCBr
Agent: [K+]
Product: CCOC(=O)C(CC)(CC)CCCCSC#N

Procedure:
Using ethyl 6-bromo-2,2-diethylhexanate as obtained in Reference Example 10and potassium thiocyanate, the title compound was produced in the same manner as in Reference Example 11.
Reaction SMILES: [Br-].Br[CH2:3][C:4]([C:6]1[C:11]([C:12]([O:14][CH3:15])=[O:13])=[CH:10][CH:9]=[CH:8][NH+:7]=1)=O.CN(C=O)C.[F:21][C:22]1[CH:30]=[CH:29][C:25]([C:26](=[S:28])[NH2:27])=[CH:24][CH:23]=1>>[F:21][C:22]1[CH:30]=[CH:29][C:25]([C:26]2[S:28][CH:3]=[C:4]([C:6]3[N:7]=[CH:8][CH:9]=[CH:10][C:11]=3[C:12]([O:14][CH3:15])=[O:13])[N:27]=2)=[CH:24][CH:23]=1
Reactant: NC(=S)c1ccc(F)cc1
Reactant: COC(=O)c1ccc[nH+]c1C(=O)CBr
Agent: [Br-]
Solvent: CN(C)C=O
Product: COC(=O)c1cccnc1-c1csc(-c2ccc(F)cc2)n1
Temperature: 25 °C
Yield: 79.8 %

Procedure:
To a solution of 2-(2-bromoacetyl)-3-(methoxycarbonyl)pyridinium bromide (1.17 g, 3.45 mmol) in 10 ml of DMF 4-fluorobenzothioamide (0.7 g, 4.51 mmol) were added and stirred at room temperature over night. For work up the reaction mixture was evaporated to dryness and the obtained crude oil purified by chromatography on silica gel (eluent: CH2CL2+0.2% methanol) to give 865 mg of the thiazole as yellow oil.
Reaction SMILES: ClCCl.[CH2:4]([OH:9])[CH2:5][C@@H:6]([OH:8])[CH3:7].[C:10]([Si:14](Cl)([C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1)[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)([CH3:13])([CH3:12])[CH3:11].[Cl-].[NH4+]>C(N(CC)CC)C>[Si:14]([O:9][CH2:4][CH2:5][C@@H:6]([OH:8])[CH3:7])([C:10]([CH3:13])([CH3:12])[CH3:11])([C:21]1[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=1)[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1
Reactant: C[C@H](O)CCO
Reactant: CC(C)(C)[Si](Cl)(c1ccccc1)c1ccccc1
Agent: [Cl-]
Agent: [NH4+]
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: C[C@H](O)CCO[Si](c1ccccc1)(c1ccccc1)C(C)(C)C
Temperature: 25 °C
Reaction time: 8 h

Procedure:
Under ice cooling, to a dichloromethane solution (20.0 ml) of (S)-1,3-butanediol (519 mg) were added triethylamine (1.04 ml) and tert-butylchlorodiphenylsilane (1.63 ml), followed by stirring at room temperature overnight. The reaction solution was poured into a saturated aqueous ammonium chloride solution, and extracted with ethyl acetate. The organic layer was washed with saturated sodium chloride solution, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The resulting residue was purified by silica gel chromatography to afford (2S)-4-{[tert-butyl(diphenyl)silyl]oxy}butan-2-ol (1.69 g).
Reaction SMILES: [CH:1]1[C:6]([CH:7]=O)=[CH:5][C:4]2[O:9][CH2:10][O:11][C:3]=2[CH:2]=1.[CH3:12][C:13]([C:15]1[CH:20]=[C:19]([O:21][CH3:22])[CH:18]=[CH:17][C:16]=1[O:23][CH3:24])=[O:14].[OH-].[Na+]>CO>[CH2:10]1[O:11][C:3]2[CH:2]=[CH:1][C:6](/[CH:7]=[CH:12]/[C:13]([C:15]3[CH:20]=[C:19]([O:21][CH3:22])[CH:18]=[CH:17][C:16]=3[O:23][CH3:24])=[O:14])=[CH:5][C:4]=2[O:9]1
Reactant: O=Cc1ccc2c(c1)OCO2
Reactant: COc1ccc(OC)c(C(C)=O)c1
Agent: [Na+]
Agent: [OH-]
Solvent: CO
Product: COc1ccc(OC)c(C(=O)/C=C/c2ccc3c(c2)OCO3)c1
Reaction time: 2 h

Procedure:
To a stirred solution of piperonal (1 g, 6.7 mmol) and 2,5-dimethoxyacetophenone (1.21 g, 6.7 mmol) in methanol (30 ml) was added 15 equivalents of aqueous sodium hydroxide (˜8 ml, 50% w/v) and the mixture stirred for 2 h. The resultant solid was collected by filtration and then recrystallised from methanol as fine, needle-like pale yellow crystals (1.70 g, 81%): mp 101° C.; 1H NMR δ (CDCl3) 3.78 (3H, s, OCH3), 3.85 (3H, s, OCH3), 6.00 (2H, s, CH2O), 6.83 (1H, d, ArH), 6.90 (1H, d, ArH), 7.00 (3H, m, ArH), 7.15 (1H, d, ArH), 7.23 (1H, d, J=15.7 Hz, ArH), 7.52 (1H, d, J=15.8 Hz, ArH); Infra red νmax (KBr)/cm−1 1652.9 (C═O); MS (rel intensity) m/z 313 ([M+H]+, 100%); Anal.
Reaction SMILES: [C:1]1([O:7][C:8](=[O:22])[NH:9][C@H:10]([C:14]2[C:19]([F:20])=[C:18]([Cl:21])[CH:17]=[CH:16][N:15]=2)[CH2:11][CH:12]=C)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.Cl.ClC(OC1C=CC=CC=1)=[O:26]>CO.O1CCOCC1.C(#N)C.CCOC(C)=O>[C:1]1([O:7][C:8](=[O:22])[NH:9][C@H:10]([C:14]2[C:19]([F:20])=[C:18]([Cl:21])[CH:17]=[CH:16][N:15]=2)[CH2:11][CH:12]=[O:26])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: C=CC[C@H](NC(=O)Oc1ccccc1)c1nccc(Cl)c1F
Reactant: O=C(Cl)Oc1ccccc1
Agent: Cl
Solvent: CC#N
Solvent: C1COCCO1
Solvent: CCOC(C)=O
Product: O=CC[C@H](NC(=O)Oc1ccccc1)c1nccc(Cl)c1F
Temperature: 25 °C
Reaction time: 1 h
Yield: 74 %

Procedure:
(S)-Phenyl(1-(4-chloro-3-fluoropyridin-2-yl)but-3-en-1-yl)carbamate: To solution of Intermediate 15B (0.710 g, 1.329 mmol) in MeOH (10 mL) was added 4 M of HCl in dioxane (10 mL) and stirred at rt for 1 h. The reaction mixture was then concentrated and dried under vacuum. The crude product was then re-dissolved in TEA (1.623 mL, 11.65 mmol) and ACN (20 mL). To the above solution was then added phenyl chloroformate (0.321 mL, 2.56 mmol) dropwise and stirred at rt for 10 min. The reaction mixture was diluted with EtOAc and washed with water. The organic layer was concentrated and the residue was purified by silica gel chromatography to yield the desired product (0.550 g, 74%). MS (ESI) m/z: 321.0 (M+H)+.
Reaction SMILES: [C:1]([C:10]1[C:18]2[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=2)[N:12]([CH2:19][CH2:20][CH2:21][C:22]([O:24]CC)=[O:23])[CH:11]=1)(=[O:9])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH3:8].C(C1C2C(=CC=CC=2)N(CCCC(OCC)=O)C=1)(=O)CCCCCC>>[C:1]([C:10]1[C:18]2[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=2)[N:12]([CH2:19][CH2:20][CH2:21][C:22]([OH:24])=[O:23])[CH:11]=1)(=[O:9])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH3:8]
Reactant: CCCCCCCC(=O)c1cn(CCCC(=O)OCC)c2ccccc12
Agent: CCCCCCC(=O)c1cn(CCCC(=O)OCC)c2ccccc12
Product: CCCCCCCC(=O)c1cn(CCCC(=O)O)c2ccccc12

Procedure:
The procedure of Ex. 2 was repeated except that ethyl 4-(3-octanoyl-1-indolyl)butyrate obtained in Ex. 3 was used in place of ethyl 4-(3-heptanoyl-1-indolyl)butyrate to give 4-(3-octanoyl-1-indolyl)butyric acid.
Reaction SMILES: [Cl:1][C:2]1[N:7]=[C:6]([Cl:8])[C:5]([C:9](Cl)=[O:10])=[CH:4][N:3]=1.C1C[O:15]CC1>O>[Cl:1][C:2]1[N:7]=[C:6]([Cl:8])[C:5]([C:9]([OH:10])=[O:15])=[CH:4][N:3]=1
Reactant: C1CCOC1
Reactant: O=C(Cl)c1cnc(Cl)nc1Cl
Solvent: O
Product: O=C(O)c1cnc(Cl)nc1Cl
Temperature: 25 °C
Reaction time: 0.83 h

Procedure:
To a solution of the 2,4-dichloropyrimidine-5-carbonyl chloride (24 mmol) in THF (24 mL) is added H2O (0.64 mL) at room temperature. The reaction mixture is stirred at room temperature for 0.83 h and then diluted with H2O. The mixture is extracted with AcOEt. The organic extracts are washed with brine, dried over Na2SO4, filtered, and concentrated in vacuo to give the crude titled compound; 1H NMR (CDCl3) δ 6.80 (brs, 1H), 9.18 (s, 1H).
Reaction SMILES: I[C:2]1[C:10]2[C:5](=[CH:6][CH:7]=[C:8]([C:11]3[S:15][N:14]=[C:13]([NH:16][CH2:17][C:18]4[CH:23]=[CH:22][C:21]([O:24][CH3:25])=[CH:20][CH:19]=4)[N:12]=3)[CH:9]=2)[N:4]([S:26]([C:29]2[CH:35]=[CH:34][C:32]([CH3:33])=[CH:31][CH:30]=2)(=[O:28])=[O:27])[CH:3]=1.[CH:36]([NH:39][C:40]1[CH:45]=[N:44][CH:43]=[C:42]([Sn](CCCC)(CCCC)CCCC)[N:41]=1)([CH3:38])[CH3:37]>CN(C=O)C.[Cu]I.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH:36]([NH:39][C:40]1[N:41]=[C:42]([C:2]2[C:10]3[C:5](=[CH:6][CH:7]=[C:8]([C:11]4[S:15][N:14]=[C:13]([NH:16][CH2:17][C:18]5[CH:23]=[CH:22][C:21]([O:24][CH3:25])=[CH:20][CH:19]=5)[N:12]=4)[CH:9]=3)[N:4]([S:26]([C:29]3[CH:30]=[CH:31][C:32]([CH3:33])=[CH:34][CH:35]=3)(=[O:27])=[O:28])[CH:3]=2)[CH:43]=[N:44][CH:45]=1)([CH3:38])[CH3:37]
Reactant: CCCC[Sn](CCCC)(CCCC)c1cncc(NC(C)C)n1
Reactant: COc1ccc(CNc2nsc(-c3ccc4c(c3)c(I)cn4S(=O)(=O)c3ccc(C)cc3)n2)cc1
Agent: [Cu]I
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Solvent: CN(C)C=O
Product: COc1ccc(CNc2nsc(-c3ccc4c(c3)c(-c3cncc(NC(C)C)n3)cn4S(=O)(=O)c3ccc(C)cc3)n2)cc1
Temperature: 90 °C
Yield: 63.5 %

Procedure:
A solution of 5-(3-iodo-1-tosyl-1H-indol-5-yl)-N-(4-methoxybenzyl)-1,2,4-thiadiazol-3-amine (0.78 g, 1.26 mmol) and N-isopropyl-6-(tributylstannyl)pyrazin-2-amine ((0.65 g, 1.52 mmol) in DMF (8 mL) was purged with argon for 15 min. To the above mixture, CuI (0.289 g, 1.52 mmol) and Pd(PPh3)4 (0.146 g, 0.126 mmol) was added and argon gas was purged for another 15 min. The reaction was heated at 90° C. for 1 h, then cooled to RT. The mixture was treated with ice cold H2O to obtain off brown precipitate. The precipitate was filtered and washed with H2O and dried. The crude was purified by neutral alumina column chromatography (eluent: 20% EtOAc in petroleum ether) to give 5-(3-(6-(isopropylamino)pyrazin-2-yl)-1-tosyl-1H-indol-5-yl)-N-(4-methoxybenzyl)-1,2,4-thiadiazol-3-amine (0.5 g, 63.5%) as an off brown solid. MS (ESI, pos. ion) m/z: 626.2 (M+1); 1H-NMR (300 MHz, DMSO-d6): δ 9.02 (brs, 1H), 8.70 (s, 1H), 8.18-8.16 (m, 1H), 7.99 (m, 2H), 7.65-7.75 (m, 3H), 7.44-7.40 (m, 3H), 7.30-7.28 (m, 2H), 1.70-7.68 (m, 1H), 6.88 (m, 1H), 4.42 (m, 2H), 3.71 (s, 3H), 2.31 (s, 3H), 1.56 (m, 6H).
Reaction SMILES: [CH3:1][N:2](C(C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[CH2:3][CH:4]([C:6]1[N:10](COCC[Si](C)(C)C)[N:9]=[CH:8][CH:7]=1)[OH:5].[ClH:38]>CO.O1CCOCC1>[ClH:38].[ClH:38].[CH3:1][NH:2][CH2:3][CH:4]([C:6]1[NH:10][N:9]=[CH:8][CH:7]=1)[OH:5]
Reactant: CN(CC(O)c1ccnn1COCC[Si](C)(C)C)C(c1ccccc1)(c1ccccc1)c1ccccc1
Agent: Cl
Solvent: CO
Solvent: C1COCCO1
Product: CNCC(O)c1ccn[nH]1
Temperature: 25 °C

Procedure:
A solution of 2-[methyl(trityl)amino]-1-(1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-pyrazol-5-yl)ethanol (0.7 g, 1.36 mmol) in 20 mL of MeOH was treated with a solution of 4N HCl in dioxane (20 mL) and refluxed overnight. After cooling to room temperature, the solvent was removed by evaporation in vacuum and the residue was suspended in EtOAc. The solid was collected by filtration and washed with hot EtOAc. A white solid 0.23 g was obtained after drying under vacuum.
Reaction SMILES: [CH:1]1[C:13]2[CH2:12][C:11]3[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=3)[C:5]=2[CH:4]=[CH:3][CH:2]=1.C(=S)=S.[C:17](Cl)([CH3:20])([CH3:19])[CH3:18].O>CCCCCC>[C:17]([C:9]1[CH:8]=[CH:7][C:6]2[C:5]3[C:13](=[CH:1][C:2]([C:5]([CH3:6])([CH3:13])[CH3:4])=[CH:3][CH:4]=3)[CH2:12][C:11]=2[CH:10]=1)([CH3:20])([CH3:19])[CH3:18]
Reactant: c1ccc2c(c1)Cc1ccccc1-2
Reactant: CC(C)(C)Cl
Solvent: S=C=S
Solvent: O
Solvent: CCCCCC
Product: CC(C)(C)c1ccc2c(c1)Cc1cc(C(C)(C)C)ccc1-2
Yield: 85 %

Procedure:
Fluorene (30.4764 g, 183.5928 mmol), FeCl3 (0.5 eq., 14.7517 g) and CS2 (300 ml) were introduced to a three-neck 1 liter flask fitted with a mechanical stirrer and hydrogen chloride trap which had been flame-dried and filled with nitrogen, and stirred. t-BuCl (2.5 eq., 50 ml) was dripped into this solution during 10 minutes. The reaction solution was stirred at room temperature for 7 hours, then water was added to quench the reaction. Next, the organic layer was extracted twice with methylene chloride, the extracted organic layer was washed with saturated salt solution, and dried using MgSO4. The dried solution was filtered, and was concentrated under reduced pressure to give a crude product (49.4598 g, brown solid). This crude product was refined by silica gel column chromatography (hexane), and the target product 2,7-di-t-butylfluorene (43.6058 g, 85%, white solid) was thus obtained. For the reaction, no further purification was carried out, but for measurement of analysis data, a sample which had been recrystallized from EtOH was used.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH3:14])[N:9]=[CH:8][CH:7]=[C:6]2[O:15][CH2:16][CH2:17][CH2:18][N:19]1C(=O)C2=CC=CC=C2C1=O.O.NN.C(O)C.CO>O1CCCC1>[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH3:14])[N:9]=[CH:8][CH:7]=[C:6]2[O:15][CH2:16][CH2:17][CH2:18][NH2:19]
Reactant: COc1cc2nccc(OCCCN3C(=O)c4ccccc4C3=O)c2cc1OC
Agent: NN
Solvent: O
Solvent: CO
Solvent: CCO
Product: COc1cc2nccc(OCCCN)c2cc1OC

Procedure:
N-(3-(6,7-Dimethoxyquinolin-4-yloxy)propyl)phthalimide (600 mg, 1.53 mM), hydrazine monohydrate (300 mg, 6.12 mM), ethanol (5 ml), methanol (5 ml) and tetrahydrofuran (5 ml) were stirred for 2 hours under reflux. The solvent was distilled off under reduced pressure, and the residue was purified by silica gel chromatography (Fuji Silysia NH Type Silica Gel, chloroform:methanol=20:1) to obtain the target substance (150 mg) as a brown oil.
Reaction SMILES: [CH2:1]([OH:6])[C:2]([F:5])([F:4])[F:3].C1(=O)O[CH2:10][CH2:9][O:8]1.C(N(CC)CC)C>[Br-].C([N+](CCCC)(CCCC)CCCC)CCC>[F:3][C:2]([F:5])([F:4])[CH2:1][O:6][CH2:10][CH2:9][OH:8]
Reactant: OCC(F)(F)F
Reactant: O=C1OCCO1
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: [Br-]
Solvent: CCN(CC)CC
Product: OCCOCC(F)(F)F

Procedure:
Trifluoroethanol (36 mL, 494 mmol), ethylene carbonate (66.0 g, 741 mmol), triethylamine (70 mL, 494 mmol) and tetrabutylammonium bromide (3.20 g, 9.90 mmol) were combined and the reaction mixture heated to reflux for 24 hours. The reaction mixture was distilled at atmospheric pressure, yielding the title product in the range 132° C. to 142° C.
Reaction SMILES: CS(O[CH2:6][C:7]1([CH2:10][C:11]#[N:12])[CH2:9][CH2:8]1)(=O)=O.S(O)(=O)(=O)C.CS(Cl)(=O)=O.[C:23]([O-:26])(=[S:25])[CH3:24].[K+].C(O)(=S)C>>[C:23]([S:25][CH2:6][C:7]1([CH2:10][C:11]#[N:12])[CH2:8][CH2:9]1)(=[O:26])[CH3:24]
Reactant: CC([O-])=S
Reactant: CS(=O)(=O)OCC1(CC#N)CC1
Agent: CC(O)=S
Agent: CS(=O)(=O)Cl
Agent: CS(=O)(=O)O
Product: CC(=O)SCC1(CC#N)CC1

Procedure:
The first step comprises converting the starting material 1,1-cyclopropanedimethanol II into the corresponding cyclic sulfite III by using thionyl chloride and in the presence of a base such as diisopropylethylamine. The cyclic sulfite III is treated with catalytic amount of sodium iodide and sodium cyanide to obtain the compound 1-(hydroxymethyl)cyclopropaneacetonitrile IV, which is converted into the corresponding mesylate 1-(methanesulfonyloxymethyl)-cyclopropaneacetonitrile V, by using methanesulfonyl chloride in the presence of a base. Compound V is treated with potassium thioacetate or thioacetic acid in the presence of a base to yield the compound 1-(acetylthiomethyl)-cyclopropaneacetonitrile VI. In the last step, compound VI is converted into 1-(mercaptomethyl)cyclopropaneacetic acid VII by reacting compound VI in a biphasic solvent system comprising toluene and aqueous NaOH for 16-18 hours.
Reaction SMILES: [OH:1][C:2]1[C:7]2[C:8]([CH3:11])=[CH:9][O:10][C:6]=2[CH:5]=[CH:4][CH:3]=1.[C:12]([O:16][CH2:17][CH3:18])(=[O:15])[CH:13]=[CH2:14].C(O)(=O)C>O1CCOCC1>[OH:1][C:2]1[C:7]2[C:8]([CH3:11])=[C:9](/[CH:14]=[CH:13]/[C:12]([O:16][CH2:17][CH3:18])=[O:15])[O:10][C:6]=2[CH:5]=[CH:4][CH:3]=1
Reactant: C=CC(=O)OCC
Reactant: Cc1coc2cccc(O)c12
Solvent: C1COCCO1
Solvent: CC(=O)O
Product: CCOC(=O)/C=C/c1oc2cccc(O)c2c1C
Yield: 20.3 %

Procedure:
A mixture of 4-hydroxy-3-methylbenzofuran (2.9 g, 20 mmoles) palladium III acetate (4.5 g, 20 mmoles), ethyl acrylate (2 g, 20 mmoles), acetic acid (50 ml) and dioxane (200 ml) was refluxed for 3 hours. The mixture was filtered and the filtrate concentrated and chromatographed to obtain 1 g of the title compound after recrystallization from toluene, m.p. 180°-182° C.
Reaction SMILES: [C:1]([C:5]1[CH:11]=[CH:10][C:8]([NH2:9])=[CH:7][CH:6]=1)([CH3:4])([CH3:3])[CH3:2].[F:12][C:13](I)([F:18])[C:14]([F:17])([F:16])[F:15].S(S([O-])=O)([O-])=O.[Na+].[Na+].C(=O)([O-])O.[Na+].S([O-])([O-])(=O)=O.C([N+](CCCC)(CCCC)CCCC)CCC.C([N+](CCCC)(CCCC)CCCC)CCC>C(OCC)(=O)C.O>[C:1]([C:5]1[CH:6]=[CH:7][C:8]([NH2:9])=[C:10]([C:13]([F:18])([F:12])[C:14]([F:17])([F:16])[F:15])[CH:11]=1)([CH3:4])([CH3:2])[CH3:3]
Reactant: CC(C)(C)c1ccc(N)cc1
Reactant: FC(F)(F)C(F)(F)I
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: O=C([O-])O
Agent: O=S(=O)([O-])[O-]
Solvent: O
Solvent: CCOC(C)=O
Product: CC(C)(C)c1ccc(N)c(C(F)(F)C(F)(F)F)c1
Temperature: 25 °C
Reaction time: 15 h
Yield: 17.8 %

Procedure:
To a liquid mixture of 40 ml of water and 40 ml of ethyl acetate were successively added 2.2 g of 4-tert-butylaniline, 5.0 g of perfluoroethyl iodide, 3.1 g of sodium dithionite, 1.5 g of sodium hydrogen carbonate and 0.6 g of tetrabutylammonium sulfate, and the resulting mixture was stirred at room temperature for 15 hours. The organic layer was separated, then the aqueous layer was extracted with 20 ml of ethyl acetate, and the organic layer were combined and washed successively with 2N aqueous hydrochloric acid, 5% aqueous sodium carbonate solution and saturated aqueous sodium chloride solution. The organic layer was dried with magnesium sulfate, then filtered, the organic solvent was distilled off under reduced pressure and the residue was purified by column chromatography to obtain 0.7 g of the intended product. Yield: 18%
Reaction SMILES: [CH2:1]([O:4][C:5]1[CH:12]=[CH:11][C:8]([CH:9]=O)=[CH:7][CH:6]=1)[CH2:2][CH3:3].[Br-].[C:14]([CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][P+](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)([OH:16])=[O:15]>C1COCC1>[CH2:1]([O:4][C:5]1[CH:12]=[CH:11][C:8]([CH:9]=[CH:21][CH2:20][CH2:19][CH2:18][CH2:17][C:14]([OH:16])=[O:15])=[CH:7][CH:6]=1)[CH2:2][CH3:3]
Reactant: O=C(O)CCCCC[P+](c1ccccc1)(c1ccccc1)c1ccccc1
Reactant: CCCOc1ccc(C=O)cc1
Agent: [Br-]
Solvent: C1CCOC1
Product: CCCOc1ccc(C=CCCCCC(=O)O)cc1
Yield: 60 %

Procedure:
This compound was synthesized from p-propoxybenzaldehyde (3.26 g, 20 mmol, prepared from 1-bromopropane and 4-hydroxybenzaldehyde) and 5-carboxypentyltriphenylphosphonium bromide (9.50 g, 20 mmol) in THF (100 mL) by a Wittig reaction. Crystallization (petroleum ether) afforded the product (3.15 g, 60%) as white crystals (mp: 52-53° C.). IR: 3450-2500, 1730 cm-1 ; 1H-NMR: 1.00 (t, 3H), 1.48 (m, 2H), 1.67 (m, 2H), 1.82 (m, 2H), 2.35 (m, 4H), 3.92 (t, 2H), 5.72+6.05 (m, 1H), 6.35 (d, 1H), 7.05 (q, 4H), 10.40 (bs, 1H). Anal. Calcd. for C16H22O3 : C, 73.25, H, 8.45%. Found: C, 73.15, H, 8.45%. Z:E=30:70.