Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [S:1]1[CH2:7][C:5](=[O:6])[NH:4][C:2]1=[S:3].[C:8]([C:12]1[CH:13]=[C:14]([CH:20]=[C:21]([C:24]([CH3:27])([CH3:26])[CH3:25])[C:22]=1[OH:23])[CH:15]=CC(=O)C)([CH3:11])([CH3:10])[CH3:9].C([O-])(=O)C.[NH4+].[C:33]1(C)[CH:38]=CC=C[CH:34]=1>>[CH3:34][C:33](=[CH:15][C:14]1[CH:13]=[C:12]([C:8]([CH3:9])([CH3:11])[CH3:10])[C:22]([OH:23])=[C:21]([C:24]([CH3:26])([CH3:25])[CH3:27])[CH:20]=1)[CH:38]=[C:7]1[S:1][C:2](=[S:3])[NH:4][C:5]1=[O:6]
Reactant: Cc1ccccc1
Reactant: CC(=O)C=Cc1cc(C(C)(C)C)c(O)c(C(C)(C)C)c1
Reactant: O=C1CSC(=S)N1
Agent: CC(=O)[O-]
Agent: [NH4+]
Product: CC(=Cc1cc(C(C)(C)C)c(O)c(C(C)(C)C)c1)C=C1SC(=S)NC1=O

Procedure:
A mixture of 1.20 g (0.009 mol) of rhodanine, 1.64 g (0.006 mol) of 3,5-di-t-butyl-4-hydroxybenzalacetone, 0.23 g (0.003 mol) of ammonium acetate and 5 of toluene was heated under reflux for 7 hours. After cooling, the precipitated crystals were recovered by filtration, washed with water and further methanol to give 0.18 g of the desired 5-(α-methyl-3,5-di-t-butyl-4-hydroxycinnamylidene)-4-oxo-2-thioxothiazolidine.
Reaction SMILES: C(Cl)(=O)C(Cl)=O.CS(C)=O.[CH2:11]([C:13]1[CH:18]=[CH:17][C:16](/[CH:19]=[CH:20]/[CH2:21][OH:22])=[CH:15][CH:14]=1)[CH3:12].C(N(CC)CC)C>C(Cl)Cl>[CH2:11]([C:13]1[CH:18]=[CH:17][C:16](/[CH:19]=[CH:20]/[CH:21]=[O:22])=[CH:15][CH:14]=1)[CH3:12]
Reactant: CCc1ccc(/C=C/CO)cc1
Agent: O=C(Cl)C(=O)Cl
Solvent: CCN(CC)CC
Solvent: ClCCl
Solvent: CS(C)=O
Product: CCc1ccc(/C=C/C=O)cc1
Reaction time: 1 h

Procedure:
General Procedure H. To a solution of oxalyl chloride (5.9 ml, 11.8 mmol, 2 M in CH2Cl2) in CH2Cl2 (20 ml) was added a solution of DMSO (1.1 ml, 15.7 mmol) in CH2Cl2 (3 ml) dropwise at −60° C. A solution of (E)-3-(4-ethylphenyl)prop-2-en-1-ol (Compound 40, 1.3 g, 7.8 mmol) in CH2Cl2 (5 ml) was cannulated slowly into the above mixture at −60° C. After the reaction was stirred at the same temperature for 1 hour, a solution of triethylamine (4.4 ml, 31.4 mmol) in CH2Cl2 (5 ml) was added into the reaction, which was stirred an additional 1 hour at −60° C. The reaction was quenched with water, and the products were extracted with CH2Cl2. The organic layer was washed with 5% aqueous NaHCO3, and brine, and dried over MgSO4. The filtered solution was concentrated in vacuo, and the residue was purified by column chromatography (silica gel, 15% ethyl acetate in hexane) to obtain the title compound as a clear oil.
Reaction SMILES: [C:1]1([N:7]2[C:12](=[O:13])[C:11]3[S:14][CH:15]=[C:16]([C:17]4[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=4)[C:10]=3[N:9]=[CH:8]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.N[C:24]1[C:28]([C:29]2C=CC3C(=CC=CC=3)C=2)=CS[C:25]=1C(OC)=O.C(OCC)(OCC)OCC.[Cl:53]C1C=CC(N)=CC=1>C(O)(=O)C>[Cl:53][C:4]1[CH:5]=[CH:6][C:1]([N:7]2[C:12](=[O:13])[C:11]3[S:14][CH:15]=[C:16]([C:17]4[CH:18]=[CH:19][C:20]5[C:21](=[CH:25][CH:24]=[CH:28][CH:29]=5)[CH:22]=4)[C:10]=3[N:9]=[CH:8]2)=[CH:2][CH:3]=1
Reactant: COC(=O)c1scc(-c2ccc3ccccc3c2)c1N
Reactant: Nc1ccc(Cl)cc1
Reactant: O=c1c2scc(-c3ccccc3)c2ncn1-c1ccccc1
Solvent: CCOC(OCC)OCC
Solvent: CC(=O)O
Product: O=c1c2scc(-c3ccc4ccccc4c3)c2ncn1-c1ccc(Cl)cc1
Yield: 92 %

Procedure:
In the same manner as the synthesis of Compound 1, methyl 3-amino-4-(naphthalen-2-yl)thiophene-2-carboxylate (43.8 mg, 0.15 mmol), triethyl orthoformate (0.32 ml), 4-chloroaniline (36.7 mg, 0.28 mmol), and acetic acid (0.04 ml) were used to give 100 mg (0.26 mmol, 92% yield) of the title compound.
Reaction SMILES: [F:1][CH:2]([F:39])[O:3][C:4]1[CH:9]=[CH:8][C:7]([NH:10][C:11]2[N:15]=[C:14]([CH:16]3[CH2:18][CH:17]3[C:19]3[CH:20]=[C:21]4[C:26](=[CH:27][CH:28]=3)[N:25](COCC[Si](C)(C)C)[C:24](=[O:37])[CH:23]=[CH:22]4)[O:13][N:12]=2)=[CH:6][C:5]=1[CH3:38].[C:40]([OH:46])([C:42]([F:45])([F:44])[F:43])=[O:41]>C(Cl)Cl>[C:40]([OH:46])([C:42]([F:45])([F:44])[F:43])=[O:41].[F:39][CH:2]([F:1])[O:3][C:4]1[CH:9]=[CH:8][C:7]([NH:10][C:11]2[N:15]=[C:14]([C@@H:16]3[CH2:18][C@H:17]3[C:19]3[CH:20]=[C:21]4[C:26](=[CH:27][CH:28]=3)[NH:25][C:24](=[O:37])[CH:23]=[CH:22]4)[O:13][N:12]=2)=[CH:6][C:5]=1[CH3:38]
Reactant: Cc1cc(Nc2noc(C3CC3c3ccc4c(ccc(=O)n4COCC[Si](C)(C)C)c3)n2)ccc1OC(F)F
Solvent: ClCCl
Solvent: O=C(O)C(F)(F)F
Product: Cc1cc(Nc2noc([C@@H]3C[C@H]3c3ccc4[nH]c(=O)ccc4c3)n2)ccc1OC(F)F
Temperature: 25 °C
Reaction time: 4 h

Procedure:
To a solution of 6-(2-(3-((4-(difluoromethoxy)-3-methylphenyl)amino)-1,2,4-oxadiazol-5-yl)cyclopropyl)-1-((2-(trimethylsilyl)ethoxy)methyl)quinolin-2(1H)-one (60 mg, 0.108 mmol) in DCM (2 mL) was added TFA (0.042 mL, 0.541 mmol) at 0° C. and the mixture was stirred at room temperature for 4 h. The reaction mixture was diluted with DCM and washed with sat. NaHCO3 solution. The organic layer was dried Na2SO4, and concentrated. The crude product which was purified by preparative HPLC on a Sunfire C18 column (150×19, 5μ) using a buffer of mobile phase A: 0.1% TFA/Mobile Phase-B: ACN to give trans-6-(2-(3-((4-(difluoromethoxy)-3-methylphenyl)amino)-1,2,4-oxadiazol-5-yl)cyclopropyl)quinolin-2(1H)-one as an off white solid (12 mg, 11%). 1H NMR (400 MHz, DMSO-d6) δ ppm 1.70-1.83 (m, 2H) 2.22 (s, 3H) 2.56-2.64 (m, 1H) 2.72-2.78 (m, 1H) 6.51 (dd, J=9.54, 2.01 Hz, 1H) 6.84-7.15 (m, 2H) 7.24 (d, J=3.01 Hz, 1H) 7.29-7.35 (m, 2H) 7.43 (dd, J=8.66, 1.88 Hz, 1H) 7.58 (d, J=1.76 Hz, 1H) 7.84 (d, J=9.54 Hz, 1H) 9.83 (s, 1H) 11.72 (s, 1H). LCMS, RT 2.23 min; LCMS (ES-API), m/z 425.2.
Reaction SMILES: [C:1]([C:3]1[C:7]([CH3:8])=[CH:6][N:5]([C:9]2[C:14]([CH3:15])=[CH:13][C:12]([CH3:16])=[CH:11][C:10]=2[CH3:17])[C:4]=1[NH:18][C:19](=O)[CH3:20])#[N:2].P(=O)(O)(O)[OH:23]>>[CH3:20][C:19]1[NH:2][C:1](=[O:23])[C:3]2[C:7]([CH3:8])=[CH:6][N:5]([C:9]3[C:14]([CH3:15])=[CH:13][C:12]([CH3:16])=[CH:11][C:10]=3[CH3:17])[C:4]=2[N:18]=1
Reactant: O=P(O)(O)O
Reactant: CC(=O)Nc1c(C#N)c(C)cn1-c1c(C)cc(C)cc1C
Product: Cc1cc(C)c(-n2cc(C)c3c(=O)[nH]c(C)nc32)c(C)c1
Reaction time: 0.5 h

Procedure:
A suspension of the compound of step B (3.200 g, 11.38 mmol) in 3 ml of 85% phosphoric acid was immersed in an oil bath preheated to 130° C. for 30 minutes. The reaction mixtures was cooled and poured onto crushed ice and stirred until solid formed and ice melted. The solid was filtered, washed with water to give a tan solid, the title compound, which was purified through silica gel column chromatography to give a tan solid. 1H NMR (CDCl3) δ 1.92(s, 6H), 2.32(s, 3H), 2.41(s, 3H), 2.45(s, 3H), 2.46(s, 3H), 6.42(d, 1H), 6.95(s, 2H) ppm.
Reaction SMILES: N.[Li].[CH:3]#[CH:4].[Si](O[CH2:13][CH:14]1[CH2:19][CH2:18][CH:17]([CH2:20][O:21]S(C2C=CC(C)=CC=2)(=O)=O)[CH2:16][CH2:15]1)(C(C)(C)C)(C)C>CS(C)=O.C1COCC1>[CH2:13]([CH:14]1[CH2:15][CH2:16][CH:17]([CH2:20][OH:21])[CH2:18][CH2:19]1)[C:3]#[CH:4]
Reactant: Cc1ccc(S(=O)(=O)OCC2CCC(CO[Si](C)(C)C(C)(C)C)CC2)cc1
Reactant: C#C
Agent: N
Agent: [Li]
Solvent: CS(C)=O
Solvent: C1CCOC1
Product: C#CCC1CCC(CO)CC1
Temperature: -78 °C
Reaction time: 1 h
Yield: 93 %

Procedure:
A 3-neck 250 mL-flask equipped with a gas inlet tube and dry-ice condenser was cooled to −78° C. and charged with liquid ammonia (40 mL). To the reaction mixture was added lithium wire (600 mg, 86.4 mmol) generating a deep blue solution. The mixture was allowed to stir for 1 hour. Acetylene, passed through a charcoal drying tube, was added to the ammonia until all the lithium had reacted and the solution turned colorless, at which time the flow of acetylene was stopped, the acetylene-inlet tube and condenser removed and the flask outfitted with a thermometer. DMSO (20 mL) was added and the ammonia evaporated with a warm water bath until the mixture reached a temperature of 30° C. The solution was stirred at this temperature for 2 hours until the solution stopped bubbling. The mixture was cooled to 5° C. and compound 84 (11.25 g, 27.3 mmol), in DMSO (10 mL), was added. The temperature was maintained at 5° C. The mixture was allowed to stir at 5° C. for 0.5 hours. Then the solution was gradually warmed to room temperature and stirred for an additional 18 hours. The brown/black reaction mixture was poured slowly over ice (300 g) and extracted with ether (4×100 mL), dried with anhydrous sodium sulfate, and concentrated in vacuo to yield a yellow oil. The oil was subsequently dissolved in THF (200 mL) and changed to a brownish color upon addition of TBAF hydrate (11.20 g, 35.5 mmol). The solution was allowed to stir for 24 hours 2 under N2 atmosphere. After stirring, the reaction was quenched with water (200 mL) and extracted with ether (3×100 mL). The ether extracts were combined and concentrated in vacuo. The crude product was purified by chromatography, on a silica gel column, eluting with 1:1 ether/petroleum ether to yield 86 (3.91 g, 93%) as a yellow oil. 1H NMR (CDCl3) δ 3.45 (d, J=6.2, 2H), 2.10 (d, J=6.2, 2H), 1.9 (s, 1H), 1.94-1.69 (m, 4H), 1.52-1.34 (m, 2H), 1.16-0.83 (m, 4H); 13C NMR (CDCl3) δ 83.8, 69.5, 69.0, 40.8, 37.7, 32.3, 29.7, 26.5.
Reaction SMILES: [CH:1]1([C:5]2[N:9]3[CH:10]=[CH:11][N:12]=[C:13]([NH2:14])[C:8]3=[C:7]([C:15]3[CH2:16][CH2:17][NH:18][CH2:19][CH:20]=3)[N:6]=2)[CH2:4][CH2:3][CH2:2]1.[C:21](O)(=[O:28])[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.CCN(C(C)C)C(C)C.CN(C=O)C>>[NH2:14][C:13]1[C:8]2[N:9]([C:5]([CH:1]3[CH2:4][CH2:3][CH2:2]3)=[N:6][C:7]=2[C:15]2[CH2:16][CH2:17][N:18]([C:21]([C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=3)=[O:28])[CH2:19][CH:20]=2)[CH:10]=[CH:11][N:12]=1
Reactant: O=C(O)c1ccccc1
Reactant: Nc1nccn2c(C3CCC3)nc(C3=CCNCC3)c12
Agent: CN(C)C(On1nnc2ccccc21)=[N+](C)C
Agent: F[B-](F)(F)F
Solvent: CN(C)C=O
Solvent: CCN(C(C)C)C(C)C
Product: Nc1nccn2c(C3CCC3)nc(C3=CCN(C(=O)c4ccccc4)CC3)c12
Temperature: 25 °C
Reaction time: 0.17 h

Procedure:
A mixture of 3-cyclobutyl-1-(1,2,3,6-tetrahydropyridin-4-yl)-imidazo[1,5-a]pyrazin-8-ylamine (20.0 mg, 0.0742 mmol), benzoic acid (9.97 mg, 0.0817 mmol), TBTU (47.7 mg, 0.148 mmol), DIEA (0.0647 mL, 0.371 mmol) and DMF (1 mL, 0.01 mol) was stirred at rt for 10 min. The reaction mixture was directly given for Gilson HPLC purification. The fractions containing the pure product were collected and concentrated in vacuo to afford the title compound as a yellow solid. 1H NMR (400 MHz, CDCl3): δ=1.96-2.06 (m, 1H) 2.09-2.23 (m, 1H) 2.40-2.63 (m, 4H) 2.72-2.93 (m, 2H) 3.57-3.88 (m, 3H) 3.98-4.34 (m, 1H) 4.47 (br. s., 1H) 5.13-5.45 (m, 2H) 5.72-6.14 (m, 1H) 7.04-7.08 (m, 2H) 7.42-7.51 (m, 5H). MS (ES+): m/z 374.07 (100) [MH+]. HPLC: tR=2.13 min (polar—5 min).
Reaction SMILES: [CH3:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:16]=[C:15]3[C:11]([CH:12]=[C:13]([C:17]([O:19]CC)=[O:18])[NH:14]3)=[CH:10][CH:9]=2)=[CH:4][CH:3]=1.[OH-].[Na+].Cl>C(O)C.C1COCC1>[CH3:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2[CH:16]=[C:15]3[C:11]([CH:12]=[C:13]([C:17]([OH:19])=[O:18])[NH:14]3)=[CH:10][CH:9]=2)=[CH:6][CH:7]=1
Reactant: CCOC(=O)c1cc2ccc(-c3ccc(C)cc3)cc2[nH]1
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: C1CCOC1
Solvent: CCO
Product: Cc1ccc(-c2ccc3cc(C(=O)O)[nH]c3c2)cc1
Reaction time: 64 h
Yield: 94.3 %

Procedure:
Into a mixed solution of ethyl 6-(4-methylphenyl)-1H-indole-2-carboxylate (0.6 g) in ethanol/THF (10/10 ml) was added at room temperature a 2 N aqueous solution of sodium hydroxide (5 ml), and the resulting mixture was stirred for 64 hours. After addition of 1 N hydrochloric acid (15 ml), the reaction mixture was concentrated under reduced pressure. Water was added to the residue, and the resulting mixture was extracted with ethyl acetate. The organic layer was washed with an aqueous saturated solution of sodium chloride and was dried with magnesium sulfate. After concentration of the organic layer under reduced pressure, the precipitated crystals were collected by filtration. The crystals were washed with hexane to obtain 6-(4-methylphenyl)-1H-indole-2-carboxylic acid (509 mg) as colorless crystals.
Reaction SMILES: [C:1]([O:6]C)(=O)[C:2]([CH3:4])=[CH2:3].CC(C)(O)C#[N:11].[S:14](=[O:18])(=[O:17])([OH:16])[OH:15]>>[S:14]([OH:18])([OH:17])(=[O:16])=[O:15].[C:1]([NH2:11])(=[O:6])[C:2]([CH3:4])=[CH2:3]
Reactant: C=C(C)C(=O)OC
Reactant: CC(C)(O)C#N
Agent: O=S(=O)(O)O
Product: C=C(C)C(N)=O

Procedure:
A process for producing the α,β-unsaturated carboxylic acid esters, for example, methyl methacrylate on a commercial scale, comprises reacting acetone cyanohydrin with concentrated sulfuric acid to form methacrylamide sulfate and thereafter esterifying this with methanol.
Reaction SMILES: [CH2:1]([N:3]1[C:7]([C:8]2[CH:9]=[C:10]([C:14]([NH:17][S:18]([CH2:21][C:22]([F:25])([F:24])[F:23])(=[O:20])=[O:19])([CH3:16])[CH3:15])[CH:11]=[CH:12][CH:13]=2)=[CH:6][C:5]([CH:26]([OH:28])[CH3:27])=[N:4]1)[CH3:2].[F:29][C:30]1[CH:35]=[CH:34][C:33](O)=[CH:32][CH:31]=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.CC(OC(/N=N/C(OC(C)C)=O)=O)C>>[F:29][C:30]1[CH:35]=[CH:34][C:33]([O:28][CH:26]([C:5]2[CH:6]=[C:7]([C:8]3[CH:9]=[C:10]([C:14]([NH:17][S:18]([CH2:21][C:22]([F:23])([F:24])[F:25])(=[O:20])=[O:19])([CH3:16])[CH3:15])[CH:11]=[CH:12][CH:13]=3)[N:3]([CH2:1][CH3:2])[N:4]=2)[CH3:27])=[CH:32][CH:31]=1
Reactant: CCn1nc(C(C)O)cc1-c1cccc(C(C)(C)NS(=O)(=O)CC(F)(F)F)c1
Reactant: Oc1ccc(F)cc1
Agent: CC(C)OC(=O)/N=N/C(=O)OC(C)C
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Product: CCn1nc(C(C)Oc2ccc(F)cc2)cc1-c1cccc(C(C)(C)NS(=O)(=O)CC(F)(F)F)c1

Procedure:
prepared following the procedure of Example 1 step 6 using the alcohol from Step 2 (121 mg, 0.29 mmol), 4-fluorophenol (49 mg, 0.44 mmol), PPh3 (113 mg, 0.44 mmol), and DIAD (85 mg, 0.44 mmol). The crude mixture was purified by column chromatography on silica eluting with 70% Et2O/iso-hexane and then by normal phase preparative HPLC to yield the ether (2.0 mg, 1%). 1H NMR (CDCl3, 500 MHz) δ 7.60-7.45 (3H, m), 7.36-7.30 (1H, m), 7.00-6.90 (4H, m), 6.28 (1H, s), 5.40 (1H, q, J=6.6 Hz), 4.90 (1H, s), 3.53-3.42 (4H, m), 1.82 (6H, s), 1.69 (3H, d, J=6.5 Hz), 1.40 (3H, t, J=7.2 Hz). MS (ES+) C24H27F4N3O3S requires: 513, found: 514 (M+H+, 100%).
Reaction SMILES: [C:1]1([CH3:10])[C:2]([S:7]([O-])=[O:8])=[CH:3][CH:4]=[CH:5][CH:6]=1.[Na+].S(Cl)([Cl:14])=O.N1C2C(=CC=CC=2)C=C1.C(=O)(O)[O-].[Na+]>ClCCl>[C:1]1([CH3:10])[C:2]([S:7]([Cl:14])=[O:8])=[CH:3][CH:4]=[CH:5][CH:6]=1
Reactant: O=S(Cl)Cl
Reactant: Cc1ccccc1S(=O)[O-]
Agent: O=C([O-])O
Agent: [Na+]
Agent: c1ccc2[nH]ccc2c1
Solvent: ClCCl
Product: Cc1ccccc1S(=O)Cl
Reaction time: 0.5 h

Procedure:
Toluenesulfinyl chloride was prepared according to Org. Syn., IV, 937 on half the scale described (that is, on 0.1 mole sodium toluenesulfinate). The crude sulfinyl chloride (15.2 g) was added dropwise to 11 g of indole dissolved in dichloromethane (200 ml) at 0° C. in the presence of 20 g of sodium bicarbonate. After 30 min at room temperature, the reaction mixture was washed well with saturated sodium bicarbonate solution, the phases separated and the organic phase dried and evaporated. The crude material was applied to a short silica gel column. Elution with dichloromethane removed a large amount of non-polar material. The product was removed with ethyl acetate. Upon recrystallization from ethyl acetate, the compound had melting point 120.5-121.5 (dec.) (corr.).
Reaction SMILES: [C:1]([CH2:3][C:4]1[CH:5]=[C:6]([CH:10]=[CH:11][CH:12]=1)[C:7]([NH2:9])=[O:8])#[N:2].Cl[CH2:14][C:15](=O)[CH3:16]>>[CH3:16][C:15]1[N:9]=[C:7]([C:6]2[CH:5]=[C:4]([CH2:3][C:1]#[N:2])[CH:12]=[CH:11][CH:10]=2)[O:8][CH:14]=1
Reactant: N#CCc1cccc(C(N)=O)c1
Reactant: CC(=O)CCl
Product: Cc1coc(-c2cccc(CC#N)c2)n1

Procedure:
A solution of 3-(cyanomethyl)benzamide (200 mg, 1.25 mmol) in 1-chloropropan-2-one (2 mL) was microwave irradiated at 120 for 20 min in a sealed tube. The mixture was concentrated to give crude product (110 mg), which was directly used to the next reaction without purification. LCMS MH+ 199.
Reaction SMILES: [CH2:1]([O:3][C:4](=[O:30])[C:5](=P(C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[CH2:6][C:7]([F:10])([F:9])[F:8])[CH3:2].O.[F:32][C:33]([F:37])([F:36])[CH:34]=O>C1COCC1>[CH2:1]([O:3][C:4](=[O:30])[C:5]([CH2:6][C:7]([F:8])([F:9])[F:10])=[CH:34][C:33]([F:37])([F:36])[F:32])[CH3:2]
Reactant: O=CC(F)(F)F
Reactant: CCOC(=O)C(CC(F)(F)F)=P(c1ccccc1)(c1ccccc1)c1ccccc1
Solvent: O
Solvent: C1CCOC1
Product: CCOC(=O)C(=CC(F)(F)F)CC(F)(F)F
Temperature: 100 °C
Yield: 86 %

Procedure:
To a solution of 4,4,4-trifluoro-2-(triphenyl-λ5-phosphanylidene)-butyric acid ethyl ester (2.0 g, 4.65 mmol) in THF (5 mL) was added 1 mL of trifluoroacetaldehyde hydrate (tech.). The mixture was sealed in a pressure tube and heated at 100° C. for 3.5 h. After cooling to 23° C., the reaction mixture was eluted through a pad of silica gel (100 g) and Na2SO4 with Et2O (100 mL) to remove the by-products triphenylphosphine oxide and water. The eluent was distilled to remove Et2O and to afford the product as a colorless liquid (1.0 g, 86%).
Reaction SMILES: [P:1]([O:16][C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)([O:9][C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1)[O:2]C1C=CC=CC=1.[CH:23](=O)[CH3:24].[O:26]1[CH2:31][CH2:30][N:29]([S:32]([NH2:35])(=[O:34])=[O:33])[CH2:28][CH2:27]1.ClC1C=CC=CC=1>CCOCC>[O:26]1[CH2:31][CH2:30][N:29]([S:32]([NH:35][CH:23]([P:1](=[O:2])([O:9][C:10]2[CH:11]=[CH:12][CH:13]=[CH:14][CH:15]=2)[O:16][C:17]2[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=2)[CH3:24])(=[O:34])=[O:33])[CH2:28][CH2:27]1
Reactant: c1ccc(OP(Oc2ccccc2)Oc2ccccc2)cc1
Reactant: NS(=O)(=O)N1CCOCC1
Reactant: CC=O
Solvent: Clc1ccccc1
Solvent: CCOCC
Product: CC(NS(=O)(=O)N1CCOCC1)P(=O)(Oc1ccccc1)Oc1ccccc1
Temperature: 100 °C

Procedure:
A mixture of 0.15 mole each of triphenyl phosphite, acetaldehyde, and morpholinosulfonylamine in 100g of chlorobenzene is warmed at 100°C. for 1.25 hrs, and the reaction mixture is stripped to 110°/0.15mm. The cooled residue is diluted with 100ml of ether, causing separation of 34.5g of crude solid product. Recrystallization of a portion from isopropyl alcohol gives a white solid, mp 104.5°-108°, 31 p nmr(DMSO-d6) -18.1 ppm.
Reaction SMILES: [C:1](=[O:20])([O:18][CH3:19])[O:2][C:3]1[CH:8]=[C:7]([N+:9]([O-:11])=[O:10])[C:6](Br)=[CH:5][C:4]=1[CH:13]1[CH2:17][CH2:16][CH2:15][CH2:14]1.[CH2:21]([N:23]1[CH2:28][CH2:27][NH:26][CH2:25][CH2:24]1)[CH3:22].C(N(CC)CC)C.ClC(OC)=O>C(O)C.ClCCl>[C:1](=[O:20])([O:18][CH3:19])[O:2][C:3]1[CH:8]=[C:7]([N+:9]([O-:11])=[O:10])[C:6]([N:26]2[CH2:27][CH2:28][N:23]([CH2:21][CH3:22])[CH2:24][CH2:25]2)=[CH:5][C:4]=1[CH:13]1[CH2:17][CH2:16][CH2:15][CH2:14]1
Reactant: CCN1CCNCC1
Reactant: COC(=O)Oc1cc([N+](=O)[O-])c(Br)cc1C1CCCC1
Agent: COC(=O)Cl
Solvent: ClCCl
Solvent: CCN(CC)CC
Solvent: CCO
Product: CCN1CCN(c2cc(C3CCCC3)c(OC(=O)OC)cc2[N+](=O)[O-])CC1
Temperature: 25 °C
Reaction time: 2 h
Yield: 76.4 %

Procedure:
A solution of (4-bromo-2-cyclopentyl-5-nitro-phenyl) methyl carbonate (800 mg, 2.33 mmol) and 1-ethylpiperazine (266 mg, 2.33 mmol) in ethanol (2.4 mL) was heated under microwave irradiation at 150° C. for 6 h, resulting in product formation with loss of the carbonate group. The reaction was concentrated in vacuo and the residue was redissolved in dichloromethane, washed with water, dried over Na2SO4, filtered and reconcentrated. The crude product was dissolved in triethylamine (648 μL, 4.65 mmol) and dichloromethane (2 mL), cooled to 0° C. and methyl chloroformate (180 μL, 2.32 mmol) was added dropwise. The reaction was warmed to room temperature and stirred for 2 h. The reaction was quenched with water and the aqueous layer was extracted with dichloromethane. The combined organics were dried over MgSO4, filtered and concentrated. Purification by silica gel chromatography (0-10% ethyl acetate/hexanes) provided 2-cyclopentyl-4-(4-ethylpiperazin-1-yl)-5-nitrophenyl methyl carbonate (672 mg, 76% yield). 1H NMR (400.0 MHz, DMSO-d6) δ 7.66 (d, J=8.6 Hz, 1H), 7.30 (d, J=8.6 Hz, 1H), 3.88 (s, 3H), 3.08-3.06 (m, 1H), 2.88 (s, 4H), 2.34-2.30 (m, 5H), 1.93-1.90 (m, 3H), 1.75-1.72 (m, 2H), 1.65-1.63 (m, 2H), 1.54-1.51 (m, 2H), 1.00 (t, J=7.1 Hz, 3H).
Reaction SMILES: [Cl:1][C:2]1[C:7]2[C:8](=[O:21])[N:9]3[CH2:20][CH2:19][CH2:18][C@H:10]3[C:11]3[N:12]([CH:13]=[N:14][C:15]=3[C:16]#[CH:17])[C:6]=2[CH:5]=[CH:4][CH:3]=1.[H-].[Na+].[CH3:24]I.O>CN(C)C=O.CCCCCC>[Cl:1][C:2]1[C:7]2[C:8](=[O:21])[N:9]3[CH2:20][CH2:19][CH2:18][C@H:10]3[C:11]3[N:12]([CH:13]=[N:14][C:15]=3[C:16]#[C:17][CH3:24])[C:6]=2[CH:5]=[CH:4][CH:3]=1
Reactant: C#Cc1ncn2c1[C@@H]1CCCN1C(=O)c1c(Cl)cccc1-2
Reactant: CI
Agent: [H-]
Agent: [Na+]
Solvent: O
Solvent: CCCCCC
Solvent: CN(C)C=O
Product: CC#Cc1ncn2c1[C@@H]1CCCN1C(=O)c1c(Cl)cccc1-2
Temperature: 25 °C
Reaction time: 4.5 h

Procedure:
250 mg (0.85 mmol) of (S)-8-chloro-1-ethynyl-11,12,13,13a-tetrahydro-9H-imidazo[1,5-a]pyrrolo[2,1-c][1,4]benzodiazepin-9-one was suspended in 5 ml of N,N-dimethylformamide. 50 mg (1 mmol) of sodium hydride dispersion (55% in oil) was washed with n-hexane and then introduced into the above suspension. After 10 minutes 0.1 ml (1.5 mmol) of methyl iodide was added thereto and the mixture was stirred at room temperature for a further 4.5 hours. The mixture was poured into 50 ml of water and extracted four times with methylene chloride. The organic extracts were washed four times with water, dried over magnesium sulphate and evaporated. After chromatography of the residue on silica gel while eluting with ethyl acetate and recrystallization from ethyl acetate and hexane there was obtained (S)-8-chloro-11,12,13,13a-tetrahydro-1-propynyl-9H-imidazo[1,5-a]pyrrolo[2,1-c][1,4]benzodiazepin-9-one of melting point 205°-20°.
Reaction SMILES: [Cl:1][C:2]1[C:3]([O:13]C)=[CH:4][C:5]2[C:9]([CH3:10])=[CH:8][S:7][C:6]=2[C:11]=1[Cl:12].Cl.N1C=CC=CC=1>O>[Cl:1][C:2]1[C:3]([OH:13])=[CH:4][C:5]2[C:9]([CH3:10])=[CH:8][S:7][C:6]=2[C:11]=1[Cl:12]
Reactant: COc1cc2c(C)csc2c(Cl)c1Cl
Agent: Cl
Solvent: O
Solvent: c1ccncc1
Product: Cc1csc2c(Cl)c(Cl)c(O)cc12
Reaction time: 2 h
Yield: 71.9 %

Procedure:
A mixture of 5.6 g of 6,7-dichloro-5-methoxy-3-methylbenzo[b]-thiophene and 50 g of pyridine hydrochloride is stirred at 190°-195° for 2 hours. The cooled reaction mixture is diluted with water and extracted with three 300 ml-portions of ether. The combined ether extracts are washed, dried and concentrated to give a tan-colored solid, mp 137°-139°. Recrystallization from hexane gives 3.8 g of 6,7-dichloro-5-hydroxy-3-methylbenzo[b]thiophene as silky needles.
Reaction SMILES: [CH:1]([C:3]1([C:6]([O:8][CH2:9][CH3:10])=[O:7])[CH2:5][CH2:4]1)=O.[C:11]1([C@@H:17]([NH2:19])[CH3:18])[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1.[C-:20]#[N:21].[K+].S([O-])(O)=O.[Na+]>C(O)C.O>[C:20]([CH:1]([NH:19][C@H:17]([C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1)[CH3:18])[C:3]1([C:6]([O:8][CH2:9][CH3:10])=[O:7])[CH2:5][CH2:4]1)#[N:21]
Reactant: [C-]#N
Reactant: C[C@H](N)c1ccccc1
Reactant: CCOC(=O)C1(C=O)CC1
Agent: O=S([O-])O
Agent: [K+]
Agent: [Na+]
Solvent: CCO
Solvent: O
Product: CCOC(=O)C1(C(C#N)N[C@@H](C)c2ccccc2)CC1
Temperature: 50 °C
Reaction time: 2 h
Yield: 81.9 %

Procedure:
An eggplant type flask was charged with 10 g of ethyl 1-formylcyclopropane-1-carboxylate to which were further added 12.8 g of (S)-1-phenylethylamine dissolved in 100 ml of ethanol, 6.9 g of potassium cyanide dissolved in 40 ml of water and 22 g of sodium hydrogen sulfite in that order at 0° C. The reaction system was stirred for 2 hours at 50° C. After confirming completion of the reaction, the reaction solution was mixed with ice water and extracted with ethyl acetate. Next, the resulting organic layer was washed with water and saturated brine, and dried over anhydrous magnesium sulfate and, after removing insoluble matter by filtration, the solvent was evaporated under a reduced pressure. Thereafter, the resulting residue was subjected to a silica gel column chromatography (hexane:ethyl acetate=8:1) to obtain 15.7 g (82%) of a diastereomer mixture in the form of colorless oil. Formation ratio of the two diastereomers was calculated under the following analytical conditions. Further, these diastereomers were able to be separated by a thin layer chromatography (hexane:ethyl acetate=4:1).