Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [C:1]([C:3]1[CH:10]=[CH:9][C:6]([CH:7]=O)=[CH:5][CH:4]=1)#[N:2].[NH2:11][C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=1[SH:18]>CS(C)=O>[C:1]([C:3]1[CH:10]=[CH:9][C:6]([C:7]2[S:18][C:13]3[CH:14]=[CH:15][CH:16]=[CH:17][C:12]=3[N:11]=2)=[CH:5][CH:4]=1)#[N:2]
Reactant: N#Cc1ccc(C=O)cc1
Reactant: Nc1ccccc1S
Solvent: CS(C)=O
Product: N#Cc1ccc(-c2nc3ccccc3s2)cc1
Temperature: 140 °C

Procedure:
44.6 g (0.34 mol) of 4-cyanobenzaldehyde and 54.4 g (0.64 mol) of o-aminobenzenethiol were dissolved in 300 ml of dimethyl sulfoxide, and the temperature of the solution was raised to 140° C. The produced water and the dimethyl sulfoxide were distilled off. After heating for one hr, the residue was cooled, water was added thereto, and the resultant precipitate was collected by filtration and washed with ethanol. The crude crystal thus obtained was recrystallized from ethyl acetate to give 2-(4'-cyanophenyl)benzothiazole. 22.4 g (0.095 mol) of the compound was dissolved in 250 ml of acetic acid, and 18.6 g (0.116 mol) of bromine was dropwise added thereto. As soon as bromine was added, a yellow bromine adduct was produced. Subsequently, 150 ml of water was added, and the mixture was stirred at 80° C. for 2 hr. It was then cooled, and the resultant precipitate was collected by filtration and washed with ethanol. The crude product thus obtained was recrystallized from ethyl acetate.
Reaction SMILES: [F:1][C:2]([F:24])([F:23])[C:3]1[CH:4]=[C:5]([C:13]2[N:17]=[CH:16][N:15](/[CH:18]=[CH:19]\[C:20](O)=[O:21])[N:14]=2)[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1.[N:25]1[CH:30]=[CH:29][N:28]=[CH:27][C:26]=1[C:31]([NH:33][NH2:34])=[O:32].C(P1(=O)OP(CCC)(=O)OP(CCC)(=O)O1)CC.CCN(C(C)C)C(C)C>ClCCl>[F:23][C:2]([F:24])([F:1])[C:3]1[CH:4]=[C:5]([C:13]2[N:17]=[CH:16][N:15](/[CH:18]=[CH:19]\[C:20]([NH:34][NH:33][C:31]([C:26]3[CH:27]=[N:28][CH:29]=[CH:30][N:25]=3)=[O:32])=[O:21])[N:14]=2)[CH:6]=[C:7]([C:9]([F:12])([F:10])[F:11])[CH:8]=1
Reactant: O=C(O)/C=C\n1cnc(-c2cc(C(F)(F)F)cc(C(F)(F)F)c2)n1
Reactant: NNC(=O)c1cnccn1
Agent: CCCP1(=O)OP(=O)(CCC)OP(=O)(CCC)O1
Solvent: ClCCl
Solvent: CCN(C(C)C)C(C)C
Product: O=C(/C=C\n1cnc(-c2cc(C(F)(F)F)cc(C(F)(F)F)c2)n1)NNC(=O)c1cnccn1
Temperature: -60 °C
Reaction time: 1 h
Yield: 19.4 %

Procedure:
In a 25 mL, 3-neck round-bottom flask, (Z)-3-(3-(3,5-bis(trifluoromethyl)phenyl)-1H-1,2,4-triazol-1-yl)acrylic acid (Example 1, Step 4; 0.5 g, 1.0 eq.) was dissolved in dichloromethane (5 mL) and cooled to −60° C. where pyrazine-2-carbohydrazide (0.216 g, 1.1 eq.) was introduced. T3P (50% in EtOAc) (3.39 mL, 4 eq.) was added dropwise followed by DIPEA (0.5 mL, 2 eq.) and the reaction mixture was stirred for 1 h at −60° C. The reaction mixture was concentrated under reduced pressure (25° C., 20 mm Hg) to afford the crude product that was purified by column chromatography (60/120 silica gel) using methanol/dichloromethane gradient (the column was packed in dichloromethane and the desired compound started eluting from 3% methanol/dichloromethane). Fractions containing the desired compounds were combined to afford (Z)—N′-(3-(3-(3,5-bis(trifluoromethyl)phenyl)-1H-1,2,4-triazol-1-yl)acryloyl)pyrazine-2-carbohydrazide (0.13 g, yield: 19.4%).
Reaction SMILES: C([C@H]1[O:9][C:8](=[O:10])[C@@:7]([C@H:17]2[CH2:21][CH2:20][C:19](=[O:22])[CH2:18]2)([C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)[O:6]1)(C)(C)C.[BH4-].[Na+]>CO.C(OCC)C>[OH:22][CH:19]1[CH2:20][CH2:21][C@H:17]([C@@:7]([OH:6])([C:11]2[CH:12]=[CH:13][CH:14]=[CH:15][CH:16]=2)[C:8]([OH:10])=[O:9])[CH2:18]1
Reactant: CC(C)(C)[C@H]1OC(=O)[C@](c2ccccc2)([C@H]2CCC(=O)C2)O1
Agent: [BH4-]
Agent: [Na+]
Solvent: CO
Solvent: CCOCC
Product: O=C(O)[C@](O)(c1ccccc1)[C@H]1CCC(O)C1
Reaction time: 0.5 h
Yield: 118.9 %

Procedure:
To a solution of 169 mg of (2R,5R)-2-(t-butyl)-5-[(1S)-3-oxocyclopentyl]-5-phenyl-1,3-dioxolan-4-one in 2 ml of methanol, 71 mg of sodium borohydride was added under cooling with ice, followed by stirring for 30 minutes at the same temperature. The reaction mixture was diluted with diethyl ether, washed with water and then brine, and dried over anhydrous magnesium sulfate. Distilling the solvent off under reduced pressure, 157 mg of the title compound was obtained as a colorless oil.
Reaction SMILES: [OH:1][C:2]1[C:3]([CH3:18])=[C:4]2[C:12](=[CH:13][C:14]=1[CH3:15])[O:11][C:7]1([CH2:10][CH2:9][CH2:8]1)[CH2:6][C:5]2=[N:16][OH:17].Cl.O1CCOCC1.C([O-])(O)=O.[Na+]>C1COCC1>[OH:17][NH:16][CH:5]1[C:4]2[C:12](=[CH:13][C:14]([CH3:15])=[C:2]([OH:1])[C:3]=2[CH3:18])[O:11][C:7]2([CH2:10][CH2:9][CH2:8]2)[CH2:6]1
Reactant: Cc1cc2c(c(C)c1O)C(=NO)CC1(CCC1)O2
Agent: Cl
Agent: O=C([O-])O
Agent: [Na+]
Solvent: C1COCCO1
Solvent: C1CCOC1
Product: Cc1cc2c(c(C)c1O)C(NO)CC1(CCC1)O2
Temperature: 0 °C
Reaction time: 0.75 h
Yield: 69.3 %

Procedure:
1.0 g of 6-hydroxy-5,7-dimethylspiro[chromene-2,1′-cyclobutan]-4(3H)-one oxime was dissolved in 20 mL of THF and cooled to 0° C. under nitrogen. 3 mL of (8M) borane-pyridine complex was added via syringe followed by 12 mL of (4 M) HCl-dioxane via a syringe pump over 45 min. After complete addition, the ice bath was removed and the reaction slowly warmed to room temperature then stirred overnight. The next day, the solution was added to sat. NaHCO3, extracted with EtOAc, washed with additional sat. NaHCO3, brine and dried over Na2SO4. The crude material was purified on a silica column eluting with 1:8 EtOAc/Hexanes to yield 699 mg of 4-(hydroxyamino)-5,7-dimethyl-3,4-dihydrospiro[chromene-2,1′-cyclobutan]-6-ol.
Reaction SMILES: [CH:1]1[C:6](=[O:7])[C:5]([OH:8])=[CH:4][O:3][C:2]=1[CH2:9][OH:10].C([O-])([O-])=O.[Cs+].[Cs+].[Br:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22]Br>CN(C=O)C>[Br:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][O:8][C:5]1[C:6](=[O:7])[CH:1]=[C:2]([CH2:9][OH:10])[O:3][CH:4]=1
Reactant: O=c1cc(CO)occ1O
Reactant: BrCCCCCBr
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: CN(C)C=O
Product: O=c1cc(CO)occ1OCCCCCBr
Temperature: 110 °C
Reaction time: 2 h
Yield: 46.3 %

Procedure:
Kojic acid (2 g, 14.1 mmol), Cs2CO3 (4.6 g, 14.1 mmol) and DMF (12 mL) were charged in a 100 ml round-bottomed flask equipped with a magnetic stirrer. 1,5-Dibromopentane (8.1 g, 35.2 mmol) was added and the reaction mixture was stirred for 2 h at 110° C. After evaporation of DMF, the reaction mixture was poured in 50 mL of H2O, extracted with CH2Cl2 (2×100 mL). The organic layer was washed with brine (2×20 mL), dried over MgSO4, filtered and evaporated to dryness. The crude compound was purified by column chromatography (SiO2; CH2Cl2:MeOH 99:1 to 95:5) to give after evaporation 5-(5-bromopentyloxy)-2-(hydroxymethyl)-4H-pyran-4-one 10 (1.9 g, 46% yield) as a brown oil.
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]([CH:8]=[CH:9][C:10]=1[C:11]([OH:14])([CH3:13])[CH3:12])[C:5]([OH:7])=[O:6].C(=O)([O-])[O-].[Cs+].[Cs+].[CH2:21](Br)[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1>CN(C=O)C>[F:1][C:2]1[CH:3]=[C:4]([CH:8]=[CH:9][C:10]=1[C:11]([OH:14])([CH3:12])[CH3:13])[C:5]([O:7][CH2:21][C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1)=[O:6]
Reactant: BrCc1ccccc1
Reactant: CC(C)(O)c1ccc(C(=O)O)cc1F
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: CN(C)C=O
Product: CC(C)(O)c1ccc(C(=O)OCc2ccccc2)cc1F
Temperature: 25 °C
Reaction time: 16 h
Yield: 21.3 %

Procedure:
To a solution of 3-fluoro-4-(1-hydroxy-1-methyl-ethyl)benzoic acid (9.1 g, 45.7 mmol) in DMF (40 mL) was added cesium carbonate (22.3 g, 68.5 mmol) followed by benzyl bromide (11.7 g, 8.1 mL, 68.5 mmol) and reaction mixture was stirred at room temperature for 16 hours. The reaction mixture was partitioned between EtOAc and H2O. The aqueous layer was extracted with EtOAc (3×20 mL). The combined organic layers were washed sequentially with H2O (3×10 mL), brine solution. The organics were separated and dried over MgSO4, filtered and concentrated in vacuo. The resulting residue was purified by silica gel column chromatography eluting with 10-20% EtOAc-hexanes to provide benzyl 3-fluoro-4-(1-hydroxy-1-methyl-ethyl)benzoate (2.8 g, 21%) ESI-MS m/z calc. 288.2. found 289.3 (M+1)+; Retention time: 1.79 min (3 min run). To a solution of benzyl 3-fluoro-4-(1-hydroxy-1-methyl-ethyl)benzoate (2.8 g, 9.71 mmol) in MeOH (50 mL) was added palladium on carbon (100 mg, 0.09 mmol) and the reaction mixture was subjected to an atmosphere of hydrogen for 16 hours. The catalyst was removed via filtration over Celite® and the solvent removed in vacuo to provide 3-fluoro-4-(1-hydroxy-1-methyl-ethyl)benzoic acid (1.8 g, 96%) as a white solid. ESI-MS m/z calc. 198.2. found 199.9 (M+1)+; Retention time: 0.91 minutes (3 min run).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[C:7]([O:9][CH3:10])[CH:6]=[C:5]([O:11][CH3:12])[C:4]=1[N:13]=[C:14]=[O:15].[CH3:16][C:17]([CH3:28])([CH3:27])[CH2:18][C:19]1[CH:26]=[CH:25][C:22]([CH2:23][NH2:24])=[CH:21][CH:20]=1>C(Cl)Cl>[CH3:12][O:11][C:5]1[CH:6]=[C:7]([O:9][CH3:10])[CH:8]=[C:3]([O:2][CH3:1])[C:4]=1[N:13]([CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH3:22])[C:14]([NH:24][CH2:23][C:22]1[CH:21]=[CH:20][C:19]([CH2:18][C:17]([CH3:28])([CH3:27])[CH3:16])=[CH:26][CH:25]=1)=[O:15]
Reactant: CC(C)(C)Cc1ccc(CN)cc1
Reactant: COc1cc(OC)c(N=C=O)c(OC)c1
Solvent: ClCCl
Product: CCCCCCCN(C(=O)NCc1ccc(CC(C)(C)C)cc1)c1c(OC)cc(OC)cc1OC
Yield: 71 %

Procedure:
The title compound was prepared according to the procedure of Example 97, but using 760 mg (3.63 mmole) 2,4,6-trimethoxyphenylisocyanate, 1.0 g (3.63 mmole) 4-(2,2-dimethylpropyl)benzylamine, and 20 ml methylene chloride. There was obtained 1.25 g product.
Reaction SMILES: [P:1]([Cl:15])(Cl)([O:3][C:4]1[C:13]2[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=2)[CH:7]=[CH:6][CH:5]=1)=[O:2].[Cl-].[CH2:17]([O:21][C:22](=[O:26])[C@@H:23]([NH3+:25])[CH3:24])[CH2:18][CH2:19][CH3:20].CCN(CC)CC>C(Cl)Cl>[Cl:15][P:1]([NH:25][C@H:23]([C:22]([O:21][CH2:17][CH2:18][CH2:19][CH3:20])=[O:26])[CH3:24])([O:3][C:4]1[C:13]2[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=2)[CH:7]=[CH:6][CH:5]=1)=[O:2]
Reactant: O=P(Cl)(Cl)Oc1cccc2ccccc12
Reactant: CCCCOC(=O)[C@H](C)[NH3+]
Agent: [Cl-]
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: CCCCOC(=O)[C@H](C)NP(=O)(Cl)Oc1cccc2ccccc12
Temperature: -78 °C

Procedure:
To 1-naphthyl dichlorophosphate in DCM (0.086 M) was added (25)-1-butoxy-1-oxopropan-2-aminium chloride (1.0 eq.). After cooling to −78° C., neat Et3N (2.0 eq.) was added and the reaction was left to warm to RT overnight. All volatiles were removed and the resulting white solid was washed with Et2O, filtered and evaporated in vacuo to obtain a colorless oil as a 1:1 mixture of diastereoisomers. 31P NMR (400 MHz, CDCl3): δ 8.39 and 8.11 ppm.
Reaction SMILES: [CH2:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[CH2:3][NH:2]1.[CH2:10]([Cl:19])[CH:11]=[CH:12][C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1.C(N(CC)CC)C.Cl>C(O)C>[ClH:19].[CH2:10]([N:2]1[CH2:3][C:4]2[C:9](=[CH:8][CH:7]=[CH:6][CH:5]=2)[CH2:1]1)[CH:11]=[CH:12][C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1
Reactant: c1ccc2c(c1)CNC2
Reactant: ClCC=Cc1ccccc1
Agent: Cl
Solvent: CCN(CC)CC
Solvent: CCO
Product: C(=Cc1ccccc1)CN1Cc2ccccc2C1
Temperature: 25 °C
Reaction time: 4 h
Yield: 34.1 %

Procedure:
The process for preparing this compound and its physical properties will be shown below. A mixture of 1.8 grams of isoindoline, 2.5 grams of cinnamyl chloride, 4 milliliters of triethylamine and 40 milliliters of ethanol is stirred for 4 hours at room temperature. After completion of the reaction, the solvent is distilled off, after which water is added to the residue and extracted with ether. The ether layer is collected and dried followed by distilling the ether off. The so obtained oily product is converted to a hydrochloride in a customary manner and then recrystallized from methyl ethyl ketone to obtain 1.4 grams (yield 34.6%) of N-cinnamylisoindoline hydrochloride as crystals having a melting point of 180°-182° C. (decomposition).
Reaction SMILES: [OH:1][C:2]1([C:15]2[CH:24]=[C:23]([CH2:25][OH:26])[C:22]3[C:17](=[CH:18][CH:19]=[CH:20][CH:21]=3)[CH:16]=2)[CH2:7][CH2:6][N:5]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[CH2:4][CH2:3]1.N1C=CC=CC=1.CC(OI1(OC(C)=O)(OC(C)=O)OC(=O)C2C=CC=CC1=2)=O>ClCCl.C(=O)(O)[O-].[Na+]>[CH:25]([C:23]1[C:22]2[C:17](=[CH:18][CH:19]=[CH:20][CH:21]=2)[CH:16]=[C:15]([C:2]2([OH:1])[CH2:7][CH2:6][N:5]([C:8]([O:10][C:11]([CH3:13])([CH3:12])[CH3:14])=[O:9])[CH2:4][CH2:3]2)[CH:24]=1)=[O:26]
Reactant: CC(C)(C)OC(=O)N1CCC(O)(c2cc(CO)c3ccccc3c2)CC1
Agent: CC(=O)OI1(OC(C)=O)(OC(C)=O)OC(=O)c2ccccc21
Agent: O=C([O-])O
Agent: [Na+]
Solvent: c1ccncc1
Solvent: ClCCl
Product: CC(C)(C)OC(=O)N1CCC(O)(c2cc(C=O)c3ccccc3c2)CC1

Procedure:
To a solution of 1.0 g (2.8 mmol) of tert-butyl 4-hydroxy-4-[4-(hydroxymethyl)-2-naphthyl]piperidine-1-carboxylate in 10 mL of anhydrous dichloromethane under an atmosphere of nitrogen was added 0.34 mL (4.2 mmol) of pyridine then 1.9 g (4.5 mmol) of Dess-Martin periodinane and the resulting solution was stirred at ambient temperature for 2 h. The mixture was diluted with a saturated aqueous sodium bicarbonate solution (5 mL), the layers were separated and the aqueous phase extracted with dichloromethane (3×10 mL). The combined organic layers were washed with brine (25 mL), dried over magnesium sulfate, filtered and evaporated in vacuo to yield the crude title compound as a colorless oil.
Reaction SMILES: [O:1]=[S:2]1[C:8]2[CH:9]=[CH:10][CH:11]=[CH:12][C:7]=2[CH2:6][N:5]([C:13]2[NH:14][C:15](=O)[C:16]3[S:21][C:20]([CH3:22])=[CH:19][C:17]=3[N:18]=2)[CH2:4][CH2:3]1.[CH2:24]([O:31][C:32]([N:34]1[CH2:38][CH2:37][CH:36]([NH2:39])[CH2:35]1)=[O:33])[C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1>>[O:1]=[S:2]1[C:8]2[CH:9]=[CH:10][CH:11]=[CH:12][C:7]=2[CH2:6][N:5]([C:13]2[N:14]=[C:15]([NH:39][CH:36]3[CH2:37][CH2:38][N:34]([C:32]([O:31][CH2:24][C:25]4[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=4)=[O:33])[CH2:35]3)[C:16]3[S:21][C:20]([CH3:22])=[CH:19][C:17]=3[N:18]=2)[CH2:4][CH2:3]1
Reactant: NC1CCN(C(=O)OCc2ccccc2)C1
Reactant: Cc1cc2nc(N3CCS(=O)c4ccccc4C3)[nH]c(=O)c2s1
Product: Cc1cc2nc(N3CCS(=O)c4ccccc4C3)nc(NC3CCN(C(=O)OCc4ccccc4)C3)c2s1

Procedure:
The title compound was prepared in analogy to Example 3-1 in Scheme 3 by using 2-(1-oxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-6-methylthieno[3,2-d]pyrimidin-4(3H)-one and benzyl-3-amino-1-pyrrolidinecarboxylate. MS obsd. (ESI+) [(M+H)+] 548.
Reaction SMILES: [F-].C([N+](CCCC)(CCCC)CCCC)CCC.[CH2:19]([CH:21]([CH2:36][CH2:37][CH2:38][CH3:39])[CH2:22][O:23][C:24]1[CH:29]=[CH:28][C:27]([C:30]#[C:31][Si](C)(C)C)=[CH:26][CH:25]=1)[CH3:20]>O1CCCC1>[CH2:19]([CH:21]([CH2:36][CH2:37][CH2:38][CH3:39])[CH2:22][O:23][C:24]1[CH:25]=[CH:26][C:27]([C:30]#[CH:31])=[CH:28][CH:29]=1)[CH3:20]
Reactant: CCCCC(CC)COc1ccc(C#C[Si](C)(C)C)cc1
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: [F-]
Solvent: C1CCOC1
Product: C#Cc1ccc(OCC(CC)CCCC)cc1
Temperature: 25 °C
Reaction time: 1.67 h
Yield: 64.5 %

Procedure:
Tetrabutylammonium fluoride (1.0 M in tetrahydrofuran, 13.2 mL, 13.2 mmol) was added to a stirred solution of [4-(2-ethylhexyloxy)phenylethynyl]trimethylsilane (3) (2.59 g, 13.2 mmol) in tetrahydrofuran (70 mL) and the solution stirred under nitrogen at room temperature for 100 min. The solvent was removed and the residue passed through a plug of silica with dichloromethane-light petroleum (1:9) as eluent to give 1-(2-ethylhexyloxy)-4-ethynylbenzene (4) (1.96 g, 99%) as a pale yellow-brown oil. (Found: C, 83.4; H, 9.85; C19H30OSi requires C, 83.4; H, 9.6%); νmax(film)/cm−1 3294 and 3317 (C≡C—H) and 2107 (C≡C); δH(400 MHz, CDCl3) 0.94 (6 H, m, CH3), 1.28-1.57 (8 H, m, CHCH2CH2CH2CH3 and CHCH2CH3), 1.74 (1 H, m, OCH2CH), 3.01 (1 H, s, CCH), 3.85 (2 H, d, J 5, OCH2CH), and 6.85 and 7.43 (4 H, AA′BB′, phenyl H); δH(100.6 MHz, CDCl3) 11.1, 14.1, 23.0, 23.8, 29.0, 30.4, 39.3, 70.5, 75.6, 83.8, 113.7, 114.4, 133.5, 159.8.
Reaction SMILES: [NH2:1][C:2]1[S:6][C:5]2[CH2:7][CH2:8][CH2:9][CH2:10][C:4]=2[C:3]=1[C:11]#[N:12].[C:13]([N:21]=[C:22]=[S:23])(=[O:20])[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1>>[C:11]([C:3]1[C:4]2[CH2:10][CH2:9][CH2:8][CH2:7][C:5]=2[S:6][C:2]=1[NH:1][C:22]([NH:21][C:13](=[O:20])[C:14]1[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=1)=[S:23])#[N:12]
Reactant: O=C(N=C=S)c1ccccc1
Reactant: N#Cc1c(N)sc2c1CCCC2
Product: N#Cc1c(NC(=S)NC(=O)c2ccccc2)sc2c1CCCC2

Procedure:
Prepared as in example 1a from 2-amino-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carbonitrile (example 5b) and benzoylisothiocyanate as a pale-yellow solid. MS 342 (MH+).
Reaction SMILES: [CH2:1]([C:3]1([CH2:6][CH3:7])[CH2:5][O:4]1)[CH3:2].[NH2:8][C:9]1[CH:10]=[C:11]([CH2:15][CH2:16][CH2:17][N:18]2[C:26](=[O:27])[C:25]3[C:20](=[CH:21][CH:22]=[CH:23][CH:24]=3)[C:19]2=[O:28])[CH:12]=[CH:13][CH:14]=1>>[CH2:1]([C:3]([OH:4])([CH2:6][CH3:7])[CH2:5][NH:8][C:9]1[CH:10]=[C:11]([CH2:15][CH2:16][CH2:17][N:18]2[C:26](=[O:27])[C:25]3[C:20](=[CH:21][CH:22]=[CH:23][CH:24]=3)[C:19]2=[O:28])[CH:12]=[CH:13][CH:14]=1)[CH3:2]
Reactant: CCC1(CC)CO1
Reactant: Nc1cccc(CCCN2C(=O)c3ccccc3C2=O)c1
Product: CCC(O)(CC)CNc1cccc(CCCN2C(=O)c3ccccc3C2=O)c1

Procedure:
Reaction between 2,2-diethyloxirane and 2-(3-(3-aminophenyl)propyl)isoindoline-1,3-dione gives 2-(3-(3-((2-ethyl-2-hydroxybutyl)amino)phenyl)propyl)isoindoline-1,3-dione.
Reaction SMILES: Cl[C:2]([O:4][CH2:5][C:6]([Cl:9])([Cl:8])[Cl:7])=[O:3].[NH2:10][C@@H:11]1[CH2:30][C@@:29]2([CH3:31])[C@@H:22]([CH2:23][CH2:24][C@@H:25]2[C:26](=[O:28])[CH3:27])[C@H:21]2[C@H:12]1[C@:13]1([CH3:36])[C@@H:18]([CH2:19][CH2:20]2)[CH2:17][C@H:16]([OH:32])[C@@H:15]([O:33][CH2:34][CH3:35])[CH2:14]1>N1C=CC=CC=1.O>[CH2:34]([O:33][C@H:15]1[CH2:14][C@@:13]2([CH3:36])[C@@H:18]([CH2:19][CH2:20][C@@H:21]3[C@@H:12]2[C@H:11]([NH:10][C:2]([O:4][CH2:5][C:6]([Cl:9])([Cl:8])[Cl:7])=[O:3])[CH2:30][C@@:29]2([CH3:31])[C@H:22]3[CH2:23][CH2:24][C@@H:25]2[C:26](=[O:28])[CH3:27])[CH2:17][C@@H:16]1[O:32][C:2]([O:4][CH2:5][C:6]([Cl:9])([Cl:8])[Cl:7])=[O:3])[CH3:35]
Reactant: CCO[C@H]1C[C@@]2(C)[C@@H](CC[C@@H]3[C@@H]2[C@H](N)C[C@]2(C)[C@@H](C(C)=O)CC[C@@H]32)C[C@@H]1O
Reactant: O=C(Cl)OCC(Cl)(Cl)Cl
Solvent: c1ccncc1
Solvent: O
Product: CCO[C@H]1C[C@@]2(C)[C@@H](CC[C@@H]3[C@@H]2[C@H](NC(=O)OCC(Cl)(Cl)Cl)C[C@]2(C)[C@@H](C(C)=O)CC[C@@H]32)C[C@@H]1OC(=O)OCC(Cl)(Cl)Cl

Procedure:
2,2,2-Trichloroethyl chloroformate (1 ml) was added to a stirred solution of 11α-amino-2β-ethoxy-3α-hydroxy-5α-pregnan-20-one (2 g) in pyridine (20 ml). After 16 hours complete reaction was not obtained. A further quantity of 2,2,2-trichloroethyl chloroformate (1 ml) was added and after 30 minutes the mixture was diluted with water (30 ml). The mixture was extracted with ether (x 2) and the extracts were washed with 2 M-HCl (x 4) and water (x 2) and dried. Evaporation of the solution left a yellow froth which was purified by column chromatography on silica eluted with ethyl acetate:petrol (1:3) to give a solid (2.5 g). A portion was crystallised from ether/petrol to give the title compound m.p. 147°-149° C., [α]D +48°.
Reaction SMILES: [C:1]1([CH2:7][CH2:8][NH:9][C:10]2[CH:15]=[CH:14][CH:13]=[C:12](B3OC(C)(C)C(C)(C)O3)[CH:11]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[NH2:25][C:26]1[C:27]([C:33]([NH:35][CH3:36])=[O:34])=[N:28][C:29](Br)=[CH:30][N:31]=1>>[NH2:25][C:26]1[C:27]([C:33]([NH:35][CH3:36])=[O:34])=[N:28][C:29]([C:12]2[CH:13]=[CH:14][CH:15]=[C:10]([NH:9][CH2:8][CH2:7][C:1]3[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=3)[CH:11]=2)=[CH:30][N:31]=1
Reactant: CNC(=O)c1nc(Br)cnc1N
Reactant: CC1(C)OB(c2cccc(NCCc3ccccc3)c2)OC1(C)C
Product: CNC(=O)c1nc(-c2cccc(NCCc3ccccc3)c2)cnc1N
Yield: 39 %

Procedure:
3-Amino-N-methyl-6-{3-[(2-phenylethyl)amino]phenyl}pyrazine-2-carboxamide was synthesized according to the procedure described above from N-(2-phenylethyl)-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)aniline and 3-amino-6-bromo-N-methyl-2-pyrazincarboxamide. Yield 39%. 1H NMR (400 MHz, CDCl3): 8.58 (s, 1H), 8.02 (br s, 1H), 7.32 (m, 3H), 7.26 (m, 3H), 7.18 (br d, 1H), 7.02 (br t, 1H), 6.64 (dd, 1H), 3.82 (br s, 1H), 3.51 (t, 2H), 3.02 (d, 3H), 2.94 (t, 2H); MS (EI) for C20H21N5O: 348 (MH+).
Reaction SMILES: [C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([S:14]([CH3:17])(=[O:16])=[O:15])[CH:10]([C:18]([OH:20])=[O:19])[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[C:21]([O-])([O-])=O.[K+].[K+].IC>CN(C=O)C>[CH3:21][O:19][C:18]([CH:10]1[N:11]([S:14]([CH3:17])(=[O:15])=[O:16])[CH2:12][CH2:13][N:8]([C:6]([O:5][C:1]([CH3:4])([CH3:2])[CH3:3])=[O:7])[CH2:9]1)=[O:20]
Reactant: O=C([O-])[O-]
Reactant: CC(C)(C)OC(=O)N1CCN(S(C)(=O)=O)C(C(=O)O)C1
Agent: [K+]
Solvent: CN(C)C=O
Solvent: CI
Product: COC(=O)C1CN(C(=O)OC(C)(C)C)CCN1S(C)(=O)=O
Temperature: 25 °C
Reaction time: 8 h
Yield: 37.2 %

Procedure:
To a solution of 4-methanesulfonyl-piperazine-1,3-dicarboxylic acid 1-tert-butyl ester (8.4 g, crude) in DMF (50 mL) was added K2CO3 (7.5 g) and iodomethane (8.5 mL) The mixture was stirred overnight at R.T. An aqueous work-up followed by purification on silica gave 4-methanesulfonyl-piperazine-1,3-dicarboxylic acid 1-tert-butyl ester 3-methyl ester (3.267 g). A solution of 4-methanesulfonyl-piperazine-1,3-dicarboxylic acid 1-tert-butyl ester 3-methyl ester (3.2 g) in dry THF (20 mL) was added via cannular to a mixture of lithium aluminium hydride (0.75 g) in THF (30 mL) at 0° C. and under N2 atmosphere. The resultant mixture was then warmed to R.T. and stirred for 2.5 h. The reaction was carefully quenched with aqueous ammonium chloride (5 mL) then filtered over Celite. An aqueous work-up followed by purification on silica gave 3-hydroxymethyl-4-methanesulfonyl-piperazine-1-carboxylic acid tert-butyl ester (1.13 g).
Reaction SMILES: Br[C:2]1[CH:9]=[CH:8][C:7]([C:10]([F:13])([F:12])[F:11])=[CH:6][C:3]=1[C:4]#[N:5].[NH2:14][NH2:15]>C(O)C>[NH2:5][C:4]1[C:3]2[C:2](=[CH:9][CH:8]=[C:7]([C:10]([F:13])([F:12])[F:11])[CH:6]=2)[NH:15][N:14]=1
Reactant: NN
Reactant: N#Cc1cc(C(F)(F)F)ccc1Br
Solvent: CCO
Product: Nc1n[nH]c2ccc(C(F)(F)F)cc12
Temperature: 95 °C

Procedure:
A solution of 8.0 g. of 2-bromo-5-trifluoromethylbenzonitrile, 3 ml. of 95% hydrazine and 40 ml. of ethanol is kept at 45°-50° C. for 30 hours. The solution is evaporated to dryness. The residue is treated with 100 ml. of 2 N hydrochloric acid, then stirred and heated to 95° C. On cooling the aqueous layer is decanted off and treated with sodium acetate to near neutrality. The precipitate is isolated by filtration and recrystallized from benzene to yield 3-amino-5-trifluoromethylindazole, M.P. 122°-123° C.
Reaction SMILES: [CH2:1]([NH:3][C:4](=[O:11])[C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1)[CH3:2].[CH3:12][Si:13](Cl)([CH3:15])[CH3:14]>>[CH2:1]([NH:3][C:4](=[O:11])[C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][C:6]=1[Si:13]([CH3:15])([CH3:14])[CH3:12])[CH3:2]
Reactant: C[Si](C)(C)Cl
Reactant: CCNC(=O)c1ccccc1
Product: CCNC(=O)c1ccccc1[Si](C)(C)C
Yield: 68.3 %

Procedure:
N-Ethylbenzamide (74.5 g, 500 mmol) and TMSCl (135.8 g, 1.25 mol) were combined according to General Method C and purified by HPLC with 1:4 ethyl acetate/hexanes to afford 75.59 g of the title compound, as a white solid, a 68% yield. m.p. 64.0°-66.0° C.