Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH:1]1([NH:6][C:7]2[N:16]=[CH:15][C:14]3[CH2:13][CH2:12][C:11]4[C:17]([C:21]([O-])=[O:22])=[N:18][N:19]([CH3:20])[C:10]=4[C:9]=3[N:8]=2)[CH2:5][CH2:4][CH2:3][CH2:2]1.[K+].C(Cl)(=O)C(Cl)=O.Cl.[CH3:32][NH:33][OH:34].C(N(CC)CC)C>ClCCl.CN(C)C=O>[CH:1]1([NH:6][C:7]2[N:16]=[CH:15][C:14]3[CH2:13][CH2:12][C:11]4[C:17]([C:21]([N:33]([OH:34])[CH3:32])=[O:22])=[N:18][N:19]([CH3:20])[C:10]=4[C:9]=3[N:8]=2)[CH2:2][CH2:3][CH2:4][CH2:5]1
Reactant: Cn1nc(C(=O)[O-])c2c1-c1nc(NC3CCCC3)ncc1CC2
Reactant: CNO
Agent: Cl
Agent: O=C(Cl)C(=O)Cl
Agent: [K+]
Solvent: CCN(CC)CC
Solvent: CN(C)C=O
Solvent: ClCCl
Product: CN(O)C(=O)c1nn(C)c2c1CCc1cnc(NC3CCCC3)nc1-2
Temperature: 25 °C
Reaction time: 6 h
Yield: 199.8 %

Procedure:
To a suspension of 400 mg (1.14 mmol) of potassium 8-(cyclopentylamino)-1-methyl-4,5-dihydro-1H-pyrazolo[4,3-h]quinazoline-3-carboxylate in 80 mL of dichloromethane and a few drops of dimethylformamide 0.11 mL (0.13 mmol) of oxalyl chloride were added at 0° C. The mixture was stirred at room temperature for 6 hours and then evaporated, redissolved in anhydrous dichloromethane and dropped into a solution of 344 mg (2.28 mmol) of N-methylhydroxylamine hydrochloride and 0.33 mL of triethylamine in 20 mL of the same solvent, cooled to 0° C. After 4 hours the mixture was washed with a saturated solution of sodium hydrogenocarbonate, dried over sodium sulfate and evaporated to dryness. The residue was triturated with diethylether and filtered to give 780 mg (60% yield) of the title compound.
Reaction SMILES: [C:1]1([CH:7]2[CH:12]([C:13]([OH:15])=O)[O:11][C:10]3[CH:16]=[CH:17][CH:18]=[CH:19][C:9]=3[O:8]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.P(Cl)(Cl)(Cl)(Cl)Cl.[CH:26]([NH2:29])([CH3:28])[CH3:27]>C1C=CC=CC=1>[CH:26]([NH:29][C:13]([CH:12]1[O:11][C:10]2[CH:16]=[CH:17][CH:18]=[CH:19][C:9]=2[O:8][CH:7]1[C:1]1[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1)=[O:15])([CH3:28])[CH3:27]
Reactant: O=C(O)C1Oc2ccccc2OC1c1ccccc1
Reactant: CC(C)N
Agent: ClP(Cl)(Cl)(Cl)Cl
Solvent: c1ccccc1
Product: CC(C)NC(=O)C1Oc2ccccc2OC1c1ccccc1
Reaction time: 2 h

Procedure:
To 22 g of (3-phenyl-1,4-benzodioxan-2-yl)-carboxylic acid in 300 cc of anhydrous benzene are added 18.1 g of PCl5 in portions with cooling. After 2 hours the reaction mixture is added to a cold solution of isopropylamine in anhydrous benzene. After stirring for 2 hours, the product is poured onto ice. The organic phase is separated, washed with H2O and finally dried over Na2SO4. The solvent is removed under vacuum. The residue is crystallised from isopropyl alcohol, m.p. = 196°-8°.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[C:6](I)[CH:5]=[C:4]([Cl:9])[C:3]=1[NH:10][C:11]1[C:20]2[CH:21]=[CH:22][NH:23][C:24](=[O:25])[C:19]=2[C:18]2[C:13](=[CH:14][CH:15]=[N:16][CH:17]=2)[N:12]=1.C(N(CC)CC)C.[CH3:33][C:34]([OH:38])([C:36]#[CH:37])[CH3:35]>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>[Cl:1][C:2]1[CH:7]=[C:6]([C:37]#[C:36][C:34]([OH:38])([CH3:35])[CH3:33])[CH:5]=[C:4]([Cl:9])[C:3]=1[NH:10][C:11]1[C:20]2[CH:21]=[CH:22][NH:23][C:24](=[O:25])[C:19]=2[C:18]2[C:13](=[CH:14][CH:15]=[N:16][CH:17]=2)[N:12]=1
Reactant: C#CC(C)(C)O
Reactant: O=c1[nH]ccc2c(Nc3c(Cl)cc(I)cc3Cl)nc3ccncc3c12
Agent: [Cu]I
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Solvent: CCN(CC)CC
Solvent: CN(C)C=O
Product: CC(C)(O)C#Cc1cc(Cl)c(Nc2nc3ccncc3c3c(=O)[nH]ccc23)c(Cl)c1
Temperature: 80 °C

Procedure:
To a solution of 6-[(2,6-dichloro-4-iodophenyl)amino]pyrido[4,3-c]-1,6-naphthyridin-10(9H)-one (50 mg, 0.10 mmol) in DMF (4 mL) were added CuI (3.94 mg, 0.02 mmol), triethylamine (30 uL, 0.20 mmol), tetrakis(triphenylphosphine)palladium (0) (12 mg, 10.4 umol), and 2-methylbut-3-yn-2-ol (17.4 mg, 0.21 mmol). The mixture was degassed by bubbling nitrogen gas and heated to 80° C. overnight. After cooling to room temperature, the mixture was diluted with water and extracted with EtOAc. The organic layers were combined, dried with MgSO4, filtered, and concentrated under reduced pressure. Purification by column chromatography on silica gel (100% CH2Cl2 to 70% CH2Cl2/30% MeOH) afforded the title compound.
Reaction SMILES: [C:1](Cl)(=[O:4])[CH:2]=[CH2:3].[CH2:6]([NH:10][C:11]1[CH:16]=[CH:15][C:14]([O:17][C:18]([F:21])([F:20])[F:19])=[CH:13][CH:12]=1)[CH2:7][CH:8]=[CH2:9].CCN(CC)CC>>[CH2:6]([N:10]([C:11]1[CH:16]=[CH:15][C:14]([O:17][C:18]([F:19])([F:20])[F:21])=[CH:13][CH:12]=1)[C:1](=[O:4])[CH:2]=[CH2:3])[CH2:7][CH:8]=[CH2:9]
Reactant: C=CCCNc1ccc(OC(F)(F)F)cc1
Reactant: C=CC(=O)Cl
Solvent: CCN(CC)CC
Product: C=CCCN(C(=O)C=C)c1ccc(OC(F)(F)F)cc1
Temperature: 25 °C
Reaction time: 8 h
Yield: 53.9 %

Procedure:
Acryloyl chloride (0.7 g, 7.8 mmol) was added dropwise to a solution of But-3-enyl-(4-trifluoromethoxy-phenyl)-amine (1.2 g, 5.2 mmol) and Et3N (1.1 g, 10.4 mmol). The mixture was stirred at ambient temperature overnight. The mixture was extracted with DCM, washed with brine, dried over anhydrous Na2SO4. The solvent was removed by reduced pressure and the residue was purified by silica gel column chromatography (eluting with petroleum ether/ethyl acetate=10/1) to give N-But-3-enyl-N-(4-trifluoromethoxy-phenyl)-acrylamide (0.8 g, 54%). 1H NMR (300 MHz, CDCl3): δ 7.35-7.18 (m, 4H), 6.38-6.35 (m, 1H), 5.96-5.93 (m, 1H), 5.78-5.74 (m, 1H), 5.68-5.64 (m, 1H), 5.08-5.01 (m, 2H), 3.84 (t, 2H, J=7.5 Hz), 2.31-2.27 (m, 2H). LC-MS: [M+1]+ 286.1.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[C:7]([O:9][CH3:10])[CH:6]=[CH:5][C:4]=1[NH:11][C:12]1[N:23]=[CH:22][CH:21]=[CH:20][C:13]=1[C:14]([NH:16][CH2:17][C:18]#[CH:19])=[O:15].[N:24]([CH2:27][C:28]1[CH:33]=[CH:32][CH:31]=[C:30](OC2C=CC=CC=2)[CH:29]=1)=[N+:25]=[N-:26].O.[O:42]=[C:43]1O[C@H]([C@H](CO)O)C([O-])=C1O.[Na+]>S([O-])([O-])(=O)=O.[Cu+2].C(O)(C)(C)C>[CH3:1][O:2][C:3]1[CH:8]=[C:7]([O:9][CH3:10])[CH:6]=[CH:5][C:4]=1[NH:11][C:12]1[N:23]=[CH:22][CH:21]=[CH:20][C:13]=1[C:14]([NH:16][CH2:17][C:18]1[N:26]=[N:25][N:24]([CH2:27][C:28]2[CH:29]=[CH:30][C:31]([O:42][CH3:43])=[CH:32][CH:33]=2)[CH:19]=1)=[O:15]
Reactant: [N-]=[N+]=NCc1cccc(Oc2ccccc2)c1
Reactant: O=C1O[C@H]([C@@H](O)CO)C([O-])=C1O
Reactant: C#CCNC(=O)c1cccnc1Nc1ccc(OC)cc1OC
Agent: [Cu+2]
Agent: O=S(=O)([O-])[O-]
Agent: [Na+]
Solvent: O
Solvent: CC(C)(C)O
Product: COc1ccc(Cn2cc(CNC(=O)c3cccnc3Nc3ccc(OC)cc3OC)nn2)cc1
Temperature: 25 °C
Reaction time: 10 h
Yield: 632.2 %

Procedure:
Compound 8 (194 mg, 1 mmol) and 2,4-dimethoxyaniline (9e, 153 mg, 1 mmol) were taken in ethylene glycol and heated at 140° C. for 6 h. Then the reaction mixture was cooled and extracted with ethyl acetate from the aqueous layer and concentrated in vacuum. The compound was further purified by column chromatography using 60-120 silica gel to obtain 2-(2,4-dimethoxyphenylamino)-N-(prop-2-ynyl)nicotinamide 10g as pure product. To a solution of 2-(2,4-dimethoxyphenylamino)-N-(prop-2-ynyl)nicotinamide (10 g, 150 mg, 0.48 mmol) and 1-(azidomethyl)-4-methoxybenzene (12c, 86 mg, 0.53 mmol) in 2:1 mixture of water and tert-butyl alcohol, sodium ascorbate (0.06 mmol) and copper (II) sulphate (0.005 mmol) were added sequentially. The reaction was stirred at room temperature for 10 h, TLC analysis indicated completion of reaction. The reaction mixture was concentrated under vacuum and extracted with EtOAc to give crude product. The crude was purified by column chromatography to afford pure product 5g (180 mg, 79%); mp: 178-180° C.; 1H NMR (500 MHz, CDCl3) δ 10.30 (s, 1H), 8.23 (m, 2H), 7.74 (dd, J=6.0, 2.0 Hz, 2H), 7.51 (s, 1H), 7.34 (brs, 1H), 7.20 (d, J=9.0 Hz, 2H), 6.86 (d, J=9.0 Hz, 2H), 6.56-6.48 (m, 3H), 5.45 (s, 2H), 4.64 (d, J=6.0 Hz, 2H), 3.87 (s, 3H), 3.79 (s, 3H), 3.79 (s, 3H); MS (ESI m/z): 475 [M+H]+. Yield: 79%
Reaction SMILES: [C:1]([C:5]1[S:6][C:7]2[CH:14]=[CH:13][CH:12]=[CH:11][C:8]=2[C:9]=1[NH2:10])(OC)=[O:2].CC(C)([O-])C.[K+].[CH:21]([NH2:23])=O.O>CS(C)=O.C(O)(=O)C>[OH:2][C:1]1[C:5]2[S:6][C:7]3[CH:14]=[CH:13][CH:12]=[CH:11][C:8]=3[C:9]=2[N:10]=[CH:21][N:23]=1
Reactant: COC(=O)c1sc2ccccc2c1N
Reactant: NC=O
Agent: CC(C)(C)[O-]
Agent: [K+]
Solvent: CC(=O)O
Solvent: CS(C)=O
Solvent: O
Product: Oc1ncnc2c1sc1ccccc12
Temperature: 90 °C

Procedure:
To a solution of 2-carbomethoxy-3-aminobenzothiophene (2.07 g.; 0.02 mole) and potassium t-butoxide (2.24 g.; 0.02 mole) in dimethylsulfoxide (30 ml.) is added an excess of formamide (ca 5 ml./g. of 2-carbomethoxy-3-aminobenzothiophene). This is heated to 90° C. until the reaction is complete as evidenced by thin layer chromatography (~30 minutes). The solution is cooled, poured into water, acidified with glacial acetic acid and the resultant solid is filtered. Washing with isopropyl alcohol and then ether yields a white solid, 1.76 g., m.p. 300°-301° C.
Reaction SMILES: Cl.[NH:2]1[CH2:7][CH2:6][CH:5]([C:8]2[C:12]3[CH:13]=[CH:14][CH:15]=[CH:16][C:11]=3[O:10][N:9]=2)[CH2:4][CH2:3]1.[C:17]([O-])([O-])=[O:18].[K+].[K+].Cl[CH2:24][CH2:25][CH2:26][O:27][C:28]1[CH:33]=[CH:32][C:31]([C:34](=[O:36])[CH3:35])=[CH:30][C:29]=1OC.CN(C)C=O>O>[O:10]1[C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=2[C:8]([CH:5]2[CH2:4][CH2:3][N:2]([CH2:24][CH2:25][CH2:26][O:27][C:28]3[CH:29]=[CH:30][C:31]([C:34](=[O:36])[CH3:35])([O:18][CH3:17])[CH2:32][CH:33]=3)[CH2:7][CH2:6]2)=[N:9]1
Reactant: O=C([O-])[O-]
Reactant: c1ccc2c(C3CCNCC3)noc2c1
Reactant: COc1cc(C(C)=O)ccc1OCCCCl
Agent: Cl
Agent: [K+]
Solvent: CN(C)C=O
Solvent: O
Product: COC1(C(C)=O)C=CC(OCCCN2CCC(c3noc4ccccc34)CC2)=CC1
Reaction time: 16 h
Yield: 47.5 %

Procedure:
A mixture of 3-(4-piperidinyl)-1,2-benzisoxazole hydrochloride (4.8 g, 20 mmol), K2CO3 (5.2 g, 40 mmol), 1-[4-(3-chloropropoxy)-3-methyoxyphenyl]ethanone (5.3 g, 22 mmol), a few crystals of KI and dimethylformamide (60 ml) was stirred at 90 C. for 16 hours. The reaction was poured into water and the aqueous mixture was extracted with ethyl acetate. The extract was washed (water), dried (MgSO4) and concentrated to afford a brown oil. The oil was chromatographed on a Waters Prep 500 utilizing silica gel columns and ethyl acetate-diethylamine (2%), as eluent. Concentration of the appropriate fractions afforded 3.9 g of product as an off-white solid. Recrystallization from absolute ethyl alcohol afforded 2.6 g (33%) of 1-[4-[3-[4-(1,2-benzisoxazol-3-yl)-1-piperidinyl]propoxy]-3-methoxypehenyl]ethanone, m.p.=102°-104° C., as colorless needles.
Reaction SMILES: Cl.[O:2]1[C:6]2[CH2:7][NH:8][CH2:9][CH2:10][C:5]=2[CH:4]=[CH:3]1.[CH2:11]([O:18][C:19]1[CH:24]=[CH:23][C:22]([CH2:25][C:26](O)=[O:27])=[CH:21][C:20]=1[O:29][CH3:30])[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1.C(N(CC)CC)C.C(P(=O)(OCC)OCC)#N>ClCCl.O>[CH2:11]([O:18][C:19]1[CH:24]=[CH:23][C:22]([CH2:25][C:26]([N:8]2[CH2:9][CH2:10][C:5]3[CH:4]=[CH:3][O:2][C:6]=3[CH2:7]2)=[O:27])=[CH:21][C:20]=1[O:29][CH3:30])[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1
Reactant: COc1cc(CC(=O)O)ccc1OCc1ccccc1
Reactant: c1cc2c(o1)CNCC2
Agent: CCOP(=O)(C#N)OCC
Agent: Cl
Solvent: O
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: COc1cc(CC(=O)N2CCc3ccoc3C2)ccc1OCc1ccccc1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
To a solution of 0.160 g (1.000 mmol) of 4,5,6,7-tetrahydrofuro[2,3-c]pyridine hydrochloride, 0.33 g (1.2 mmol) of 4-benzyloxy-3-methoxyphenylacetic acid and 0.55 ml (4.0 mmol) of triethylamine in 30 ml of dichloromethane, 0.24 g (1.5 mmol) of diethyl cyanophosphonate was added dropwise under ice-cooling, followed by overnight stirring at room temperature. The reaction mixture was poured into water and extracted with dichloromethane 2 times. The combined organic layer was washed with water and dried over anhydrous sodium sulfate; the solvent was distilled off under reduced pressure. The resulting crude product was purified by silica gel column chromatography (hexane/ethyl acetate=3/1 to 2/1) to yield the desired product.
Reaction SMILES: [NH2:1][C:2]1[CH:10]=[CH:9][C:8]([O:11][CH3:12])=[C:7]([O:13][CH3:14])[C:3]=1[C:4]([OH:6])=O.[O-:15][C:16]#[N:17].[K+].[OH-].[Na+].C(O)(C)C>C(O)(=O)C.O>[OH:15][C:16]1[N:17]=[C:4]([OH:6])[C:3]2[C:2](=[CH:10][CH:9]=[C:8]([O:11][CH3:12])[C:7]=2[O:13][CH3:14])[N:1]=1
Reactant: N#C[O-]
Reactant: COc1ccc(N)c(C(=O)O)c1OC
Agent: [K+]
Agent: [Na+]
Agent: [OH-]
Solvent: O
Solvent: CC(C)O
Solvent: CC(=O)O
Product: COc1ccc2nc(O)nc(O)c2c1OC
Temperature: 60 °C
Reaction time: 2 h
Yield: 60.8 %

Procedure:
2-Amino-5,6-dimethoxybenzoic acid (10.5 g, 53.2 mM) was dissolved in glacial acetic acid (100 ml) and potassium cyanate (10.8 g, 133.0 mM) in 120 ml H2O was added gradually and stirred for 2 hours at 60° C. After cooling the reaction mixture to 20° C., sodium hydroxide pellets (78.2 g, 196 mole) were added while maintaining the temperature below 60° C. The reaction mixture was then heated at 90° C. for 45 minutes. Upon cooling in an ice bath, the sodium salt of the product precipitated, was filtered, resuspended in H2O (120 ml), acidified (pH 3) with concentrated HCl, cooled, and filtered to give the crude product. Trituration with warm isopropanol afforded (60.8%) of a white solid, mp 266°-268° C.
Reaction SMILES: CS(O[CH2:6][C:7]([NH:10][C:11]1[CH:16]=[C:15]([Cl:17])[N:14]=[C:13](Cl)[N:12]=1)([CH3:9])[CH3:8])(=O)=O.C(=O)([O-])[O-:20].[K+].[K+]>O1CCOCC1.O>[Cl:17][C:15]1[CH:16]=[C:11]2[NH:10][C:7]([CH3:9])([CH3:8])[CH2:6][N:12]2[C:13](=[O:20])[N:14]=1
Reactant: CC(C)(COS(C)(=O)=O)Nc1cc(Cl)nc(Cl)n1
Reactant: O=C([O-])[O-]
Agent: [K+]
Solvent: C1COCCO1
Solvent: O
Product: CC1(C)Cn2c(cc(Cl)nc2=O)N1
Temperature: 80 °C
Reaction time: 2 h

Procedure:
To a solution of 2-((2,6-dichloropyrimidin-4-yl)amino)-2-methylpropyl methanesulfonate (3.00 g, 9.55 mmol) in 1,4-dioxane (15 mL) and water (15 mL) was added potassium carbonate (4.62 g, 33.4 mmol). The reaction mixture was stirred at 80° C. for 2 h, filtered, extracted with ethyl acetate (5 mL×2), dried over anhydrous Na2SO4, filtered and concentrated to give the crude product, which was used into next step without further purification.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]([C:21]2[CH:26]=[CH:25][C:24]([Cl:27])=[CH:23][CH:22]=2)[N:9]2[CH2:14][CH2:13][N:12]([CH2:15][C:16]([O:18]C)=[O:17])[C:11](=[O:20])[CH2:10]2)=[CH:4][CH:3]=1.O.[OH-].[Li+]>C1COCC1.CO.O>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([CH:8]([C:21]2[CH:22]=[CH:23][C:24]([Cl:27])=[CH:25][CH:26]=2)[N:9]2[CH2:14][CH2:13][N:12]([CH2:15][C:16]([OH:18])=[O:17])[C:11](=[O:20])[CH2:10]2)=[CH:6][CH:7]=1
Reactant: COC(=O)CN1CCN(C(c2ccc(Cl)cc2)c2ccc(Cl)cc2)CC1=O
Agent: [Li+]
Agent: [OH-]
Solvent: O
Solvent: CO
Solvent: C1CCOC1
Product: O=C(O)CN1CCN(C(c2ccc(Cl)cc2)c2ccc(Cl)cc2)CC1=O
Reaction time: 8 h
Yield: 88 %

Procedure:
To a solution of methyl 2-(4-(bis(4-chlorophenyl)methyl)-2-oxopiperazin-1-yl)acetate (160 mg, 393 μmol) in THF/MeOH/H2O=5:5:1 (5.5 mL) was added lithium hydroxide monohydrate (49.5 mg, 1.179 mmol) and the resulting solution was stirred overnight. The solvent was evaporated, diluted with water, adjusted to pH=5 with 10% HCl, extracted with DCM, dried over Na2SO4, filtered and evaporated to dryness under high vacuum. The residue was loaded onto flash column (SiO2, DCM to DCM/MeOH=100:5 to 100:10 to 100:15 to 100:20) to give 2-(4-(bis(4-chlorophenyl)methyl)-2-oxopiperazin-1-yl)acetic acid (136 mg) as a white solid.
Reaction SMILES: [SH:1][CH2:2][C:3]([O:5][CH3:6])=[O:4].[C:7]1([C:13]([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)O)[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1.FC(F)(F)C(O)=O>C(Cl)(Cl)Cl>[CH3:6][O:5][C:3](=[O:4])[CH2:2][S:1][C:13]([C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1)([C:21]1[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=1)[C:15]1[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=1
Reactant: COC(=O)CS
Reactant: OC(c1ccccc1)(c1ccccc1)c1ccccc1
Solvent: ClC(Cl)Cl
Solvent: O=C(O)C(F)(F)F
Product: COC(=O)CSC(c1ccccc1)(c1ccccc1)c1ccccc1
Temperature: 25 °C
Reaction time: 1 h
Yield: 91.3 %

Procedure:
To a mixture of methyl mercaptoacetate (5.30 g, 50 mmol) and triphenylmethanol (13.0 g, 50 mmol) in chloroform (20 mL) was added trifloroacetic acid (5 mL) in 5 min. After stirring at room temperature for 1 h, the volatiles were removed in vacuo. The crude product was purified by recrystallization (dichloromethane/Hexane=½) to provide Tritylsulfanyl-acetic acid methyl ester (15.9 g, 91%). 1H NMR (300 MHz, CDCl3) δ 7.44-7.38 (m, 6H), 7.34-7.18 (m, 9H), 3.58 (s, 3H), 2.98 (s, 2H).
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][C:16]1[CH:22]=[CH:21][C:19]([NH2:20])=[CH:18][CH:17]=1.[C:23]([CH:27]1[CH2:32][CH2:31][C:30](=O)[CH2:29][CH2:28]1)([CH3:26])([CH3:25])[CH3:24].C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].O>CN(C)C=O.C(OCC)(=O)C>[C:23]([CH:27]1[CH2:32][CH2:31][CH:30]([NH:20][C:19]2[CH:21]=[CH:22][C:16]([O:15][C:6]3[C:5]4[C:10](=[CH:11][C:12]([O:13][CH3:14])=[C:3]([O:2][CH3:1])[CH:4]=4)[N:9]=[CH:8][CH:7]=3)=[CH:17][CH:18]=2)[CH2:29][CH2:28]1)([CH3:26])([CH3:25])[CH3:24]
Reactant: CC(C)(C)C1CCC(=O)CC1
Reactant: COc1cc2nccc(Oc3ccc(N)cc3)c2cc1OC
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: [Na+]
Solvent: CCOC(C)=O
Solvent: CN(C)C=O
Solvent: O
Product: COc1cc2nccc(Oc3ccc(NC4CCC(C(C)(C)C)CC4)cc3)c2cc1OC
Temperature: 60 °C
Reaction time: 1 h
Yield: 11.4 %

Procedure:
4-(6,7-Dimethoxy-4-quinolyloxy)aniline (300 mg) was dissolved in N,N-dimethylformamide (10 ml) to prepare a solution. 4-Tert-butylcyclohexanone (200 mg) was then added to the solution, and the mixture was stirred at 60° C. for one hr. The reaction solution was cooled to room temperature before sodium triacetoxy borohydride (400 mg) was added thereto. The mixture was then stirred at room temperature for 3 hr. Water and ethyl acetate were added to the reaction solution, and the mixture was extracted with ethyl acetate. The extract was washed with saturated brine and was dried over sodium sulfate. The solvent was removed by evaporation under the reduced pressure, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (50 mg, yield 11%).
Reaction SMILES: [CH2:1]([C@H:8]1[CH2:12][O:11][C:10](=[O:13])[N:9]1[C:14](=[O:19])[CH2:15][O:16][CH2:17][CH3:18])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(N([CH2:25][CH3:26])CC)C.[O-]S(C(F)(F)F)(=O)=O.C([B+]CCCC)CCC.[CH2:44]([O:51][C:52]1[CH:59]=[CH:58][C:55]([CH:56]=[O:57])=[C:54](C)[CH:53]=1)[C:45]1[CH:50]=[CH:49][CH:48]=[CH:47][CH:46]=1>ClCCl>[CH2:1]([C@H:8]1[CH2:12][O:11][C:10](=[O:13])[N:9]1[C:14](=[O:19])[C@@H:15]([O:16][CH2:17][CH3:18])[C@@H:56]([C:55]1[CH:58]=[CH:59][C:52]([O:51][CH2:44][C:45]2[CH:50]=[CH:49][CH:48]=[CH:47][CH:46]=2)=[CH:53][C:54]=1[CH2:25][CH3:26])[OH:57])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: CCN(CC)CC
Reactant: Cc1cc(OCc2ccccc2)ccc1C=O
Reactant: CCOCC(=O)N1C(=O)OC[C@@H]1Cc1ccccc1
Agent: CCCC[B+]CCCC
Agent: O=S(=O)([O-])C(F)(F)F
Solvent: ClCCl
Product: CCO[C@H](C(=O)N1C(=O)OC[C@@H]1Cc1ccccc1)[C@H](O)c1ccc(OCc2ccccc2)cc1CC
Temperature: -78 °C
Reaction time: 0.83 h
Yield: 57.1 %

Procedure:
(S)-4-Benzyl-3-ethoxyacetyl-oxazolidin-2-one (6.21 g, 24 mmol) (for the preparation of (S)-4-benzyl-3-ethoxyacetyl-oxazolidin-2-one see: D. Haigh, H. C. Birrell, B. C. C. Cantello, D. S. Eggleston, R. C. Haltiwanger, R. M. Hindley, A. Ramaswamy, N. C. Stevens, Tetrahedron: Asymmetry 1999, 10, 1353–1367) was dissolved in dry dichloromethane (135 ml) under an argon atmosphere and the solution was cooled to −78° C. Triethylamine (3.98 ml, 28 mmol) was added, followed by the slow addition, over approximately 20 min, of di-n-butylboron triflate (1 M solution in dichloromethane, 25 ml, 25 mmol) such that the reaction temperature was kept below −70° C. The mixture was stirred at −78° C. for 50 min, the cooling bath was replaced with an ice bath and the mixture stirred at 0° C. for additional 50 min before being recooled to −78° C. A solution of 4-benzyloxy-2-methyl-benzaldehyde (6 g, 24 mmol) in dry dichloromethane (65 ml) was added over ca. 45 min, such that the reaction temperature was maintained below −70° C. The resulting mixture was stirred at −78° C. for 45 min, warmed from −78° C. to 0° C. and stirred at 0° C. for a further 1.5 h. The reaction mixture was poured onto ice water/brine and extracted two times with dichloromethane. The combined extracts were washed with brine and dried over sodium sulfate. The solvent was removed under reduced pressure and the residue purified by column chromatography (silica gel, cyclohexane/AcOEt) to give 6.9 g (13.7 mmol, 58%) of the title compound as yellow foam. According to 1H-NMR spectroscopy, one of the four isomers is strongly predominating. The configuration was tentatively assigned as 2S,3R according to D. Haigh et al., Tetrahedron: Asymmetry 1999, 10, 1353–1367.
Reaction SMILES: Br[CH2:2][C:3]#[N:4].[C:5](=[S:10])([O:7][CH2:8][CH3:9])[S-:6].[K+]>C(O)C.O>[O:7]([CH2:8][CH3:9])[C:5]([S:10][CH2:2][C:3]#[N:4])=[S:6]
Reactant: N#CCBr
Reactant: CCOC(=S)[S-]
Agent: [K+]
Solvent: O
Solvent: CCO
Product: CCOC(=S)SCC#N
Temperature: 25 °C
Reaction time: 16 h
Yield: 90.7 %

Procedure:
A solution of bromoacetonitrile (12.4 g) and potassium O-ethyl dithiocarbonate (16.0 g) in ethanol (200 mL) were allowed to stir at room temperature for 16 hours. The reaction was diluted with water (100 mL) and the organics extracted with diethyl ether. The combined organic layers were washed twice with water, then brine and dried over anhydrous magnesium sulfate. The solvent was evaporated and the residue purified by column chromatography (silica-gel 60, 70-230 mesh) eluting with 4:6 ethyl acetate:petroleum spirit 40-60° C. to afford the title compound as a yellow oil (14.6 g, 90.7%). 1H-nmr (CDCl3) δ 1.48 (t, 3H); 3.88 (s, 2H); 4.72 (q, 2H). 13C-nmr (CDCl3) δ 13.7, 21.3, 71.5, 115.7, 209.2.
Reaction SMILES: S(=O)(=O)(O)[OH:2].[CH3:6][C:7]([CH3:16])=[CH:8][CH2:9][C@@H:10]1O[C@@:11]1([CH:14]=[CH2:15])[CH3:13]>>[CH3:6][C:7]([CH3:16])=[CH:8][CH:9]([OH:2])/[CH:10]=[C:11](/[CH:14]=[CH2:15])\[CH3:13]
Reactant: C=C[C@@]1(C)O[C@H]1CC=C(C)C
Reactant: O=S(=O)(O)O
Product: C=C/C(C)=C/C(O)C=C(C)C
Reaction time: 1 h
Yield: 70 %

Procedure:
To 500 ml. of 50% aqueous sulphuric acid acid cooled between -5° and 0° were added dropwise 75 g. of transepoxyocimene prepared according to the description of paragraph (a) above. The mixture was vigorously stirred for one hour wile the temperature was allowed to slowly rise to 20-25°. It was extracted with methylene chloride, the extract was washed several times with water, with a saturated aqueous solution of sodium carbonate and finally with water. The extract was dried, concentrated and distilled. Thus secondary trans-ocimenol was obtained with a yield of 70-80%.
Reaction SMILES: [Cl:1][CH2:2]/[CH:3]=[CH:4]/[CH2:5][O:6][C:7]1[CH:14]=[CH:13][C:12]([N+:15]([O-:17])=[O:16])=[CH:11][C:8]=1[CH:9]=O.[C:18]([O:24][CH3:25])(=[O:23])[CH2:19][C:20]([CH3:22])=O.[NH2:26]/[C:27](/[CH3:33])=[CH:28]\[C:29]([O:31][CH3:32])=[O:30]>C(O)(C)C>[Cl:1][CH2:2]/[CH:3]=[CH:4]/[CH2:5][O:6][C:7]1[CH:14]=[CH:13][C:12]([N+:15]([O-:17])=[O:16])=[CH:11][C:8]=1[CH:9]1[C:19]([C:18]([O:24][CH3:25])=[O:23])=[C:20]([CH3:22])[NH:26][C:27]([CH3:33])=[C:28]1[C:29]([O:31][CH3:32])=[O:30]
Reactant: COC(=O)CC(C)=O
Reactant: COC(=O)/C=C(/C)N
Reactant: O=Cc1cc([N+](=O)[O-])ccc1OC/C=C/CCl
Solvent: CC(C)O
Product: COC(=O)C1=C(C)NC(C)=C(C(=O)OC)C1c1cc([N+](=O)[O-])ccc1OC/C=C/CCl
Yield: 48.8 %

Procedure:
5.2 g of 2-[(E)-4-chloro-2-butenyloxy]-5-nitrobenzaldehyde, 2.4 g of methyl acetoacetate and 2.3 g of methyl 3-aminocrotonate was dissolved in 30 ml of iso-propanol, and the solution obtained was refluxed for 3.5 hours under heating. After cooling, the precipitated crystals were collected by filtration to give 4.4 g of dimethyl 4-[2-[(E)-4-chloro-2-butenyloxy]-5-nitrophenyl]-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate. (mp. 206°-207° C.). The product obtained was used directly for the next process without purification.