Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [O:1]1[CH2:6][CH2:5][C:4](=O)[CH2:3][CH2:2]1.[NH:8]([C:10]([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11])[NH2:9].C([BH3-])#N.[Na+]>CO>[O:1]1[CH2:6][CH2:5][CH:4]([NH:9][NH:8][C:10]([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11])[CH2:3][CH2:2]1
Reactant: CC(C)(C)OC(=O)NN
Reactant: O=C1CCOCC1
Agent: [BH3-]C#N
Agent: [Na+]
Solvent: CO
Product: CC(C)(C)OC(=O)NNC1CCOCC1
Temperature: 25 °C
Reaction time: 3 h

Procedure:
Tetrahydro-4H-pyran-4-one (9.69 g, 97 mmol) was added to a solution of 1,1-dimethylethyl hydrazinecarboxylate (14.07 g, 106 mmol) in methanol (100 mL) and stirred at room temperature for 3 h. The solvent was removed in vacuo, and the crude residue was suspended in acetic acid (140 mL). Next added sodium cyanoborohydride (6.69 g, 106 mmol) in portions over 3 minutes. The contents were stirred at room temperature for 60 h. The solvent was removed in vacuo, and the crude residue was suspended in DCM (100 mL). The reaction mixture was adjusted to pH 7 with 6N NaOH. The layers were separated, and the aq. layer extracted with DCM. The combined organic layers were washed with saturated NaHCO3, and brine. The organic layer was dried over MgSO4, filtered, and concentrated in vacuo to afford the product as a solid, 18.4 g (88%). 1H NMR (400 MHz, DMSO-d6) δ ppm 1.22 (m, 2 H), 1.39 (s, 9 H), 1.43-1.48 (m, 1 H), 1.59-1.69 (m, 2 H), 2.82-2.98 (m, 1 H), 3.20-3.32 (m, 2 H), 3.80 (d, J=11.62 Hz, 2 H), 4.36 (br. s., 1 H), 8.07-8.34 (m, 1 H).
Reaction SMILES: C[N:2]([CH3:13])[C:3]1[CH:12]=[CH:11][C:6]([C:7]([NH:9]N)=[O:8])=[CH:5]C=1.[N:14]#N.C(Cl)(=O)C1C=CC=C(C(Cl)=O)C=1.[N:28]1[CH:33]=CC=CC=1>>[CH2:12]1[CH:11]2[CH:6]([C:7]3[O:8][N:14]=[C:33]([NH2:28])[N:9]=3)[CH2:5][N:2]([CH2:13]2)[CH2:3]1
Reactant: c1ccncc1
Reactant: CN(C)c1ccc(C(=O)NN)cc1
Reactant: N#N
Agent: O=C(Cl)c1cccc(C(=O)Cl)c1
Product: Nc1noc(C2CN3CCC2C3)n1

Procedure:
First, 10.31 g (57.53 mmol) of 4-Dimethylaminobenzhydrazide and then 100 ml of dehydrated pyridine are put in a three neck flask (capacity: 500 ml). Next, a cooling tube is attached to the mouth of the flask and N2 gas is installed inside. 4-Dimethylaminobenzhydrazide was dissolved in the pyridine by mixing at a room temperature. Further, 6.26 g (30.83 mmol) of Isophthaloyl Chloride was added to the system of reaction from a side tube of the three neck flask, and for 8 hours the pyridine was refluxed. After the reaction is done, pyridine is removed from the system of reaction by distillation. The reactant is washed well and is vacuum dried in a vacuum desiccator. Consequently an oxadiazole precursor is formed. The above reaction is expressed by the chemical formula 19 below. ##STR13## 2. The synthesis of an oxadiazole compound.
Reaction SMILES: [CH2:1]([C:4]1([O:10][Si:11]([CH3:14])([CH3:13])[CH3:12])[CH2:9][CH2:8][CH2:7][CH2:6][CH2:5]1)[C:2]#[CH:3].N(C(C)(C)C#N)=NC(C)(C)C#N.[CH2:27]([SnH:31]([CH2:36][CH2:37][CH2:38][CH3:39])[CH2:32][CH2:33][CH2:34][CH3:35])[CH2:28][CH2:29][CH3:30]>>[CH2:36]([Sn:31]([CH2:27][CH2:28][CH2:29][CH3:30])([CH2:32][CH2:33][CH2:34][CH3:35])[CH2:3]/[CH:2]=[CH:1]/[C:4]1([O:10][Si:11]([CH3:14])([CH3:13])[CH3:12])[CH2:5][CH2:6][CH2:7][CH2:8][CH2:9]1)[CH2:37][CH2:38][CH3:39]
Reactant: C#CCC1(O[Si](C)(C)C)CCCCC1
Reactant: CCCC[SnH](CCCC)CCCC
Agent: CC(C)(C#N)N=NC(C)(C)C#N
Product: CCCC[Sn](C/C=C/C1(O[Si](C)(C)C)CCCCC1)(CCCC)CCCC
Temperature: 80 °C

Procedure:
To a stirred mixture of 31.5 g of 1-propargyl-1-trimethylsilyloxycyclohexane and 150 mg of azobisisobutyronitrile is added 41 ml of tri-n-butyltin hydride. The stirred mixture is heated to about 80° C. The initial exothermic maintained at 130°-135° C. for one hour.
Reaction SMILES: Br[C:2]1[C:7](=[O:8])[N:6]([CH2:9][C:10]2[CH:15]=[CH:14][C:13]([C:16]3[C:17]([C:22]#[N:23])=[CH:18][CH:19]=[CH:20][CH:21]=3)=[CH:12][CH:11]=2)[C:5]([CH2:24][CH2:25][CH3:26])=[N:4][C:3]=1[CH3:27].[C:28]1([OH:34])[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1.[OH-].[K+].CS(C)=O>C(OCC)(=O)C>[CH3:27][C:3]1[N:4]=[C:5]([CH2:24][CH2:25][CH3:26])[N:6]([CH2:9][C:10]2[CH:15]=[CH:14][C:13]([C:16]3[C:17]([C:22]#[N:23])=[CH:18][CH:19]=[CH:20][CH:21]=3)=[CH:12][CH:11]=2)[C:7](=[O:8])[C:2]=1[O:34][C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1
Reactant: CCCc1nc(C)c(Br)c(=O)n1Cc1ccc(-c2ccccc2C#N)cc1
Reactant: Oc1ccccc1
Agent: [K+]
Agent: [OH-]
Solvent: CS(C)=O
Solvent: CCOC(C)=O
Product: CCCc1nc(C)c(Oc2ccccc2)c(=O)n1Cc1ccc(-c2ccccc2C#N)cc1
Temperature: 150 °C
Reaction time: 12 h
Yield: 13.6 %

Procedure:
A mixture of 4′-[(5-bromo-4-methyl-6-oxo-2-propylpyrimidin-1(6H)-yl)methyl]biphenyl-2-carbonitrile (0.5 g), phenol (0.16 g), 8 M potassium hydroxide solution (0.2 mL) and dimethyl sulfoxide (5 mL) was stirred at 150° C. for 12 hr. The reaction mixture was diluted with ethyl acetate, washed with water and then with saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure and the residue was purified by silica gel column chromatography to give the title compound as a colorless amorphous solid (0.07 g, 13%).
Reaction SMILES: [Br:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[S:8](CC(N)=O)(=[O:10])=[O:9].Cl[CH2:16][C:17]([N:19]([CH2:22][CH3:23])[CH2:20][CH3:21])=[O:18]>>[Br:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[S:8]([CH2:16][C:17]([N:19]([CH2:22][CH3:23])[CH2:20][CH3:21])=[O:18])(=[O:10])=[O:9]
Reactant: CCN(CC)C(=O)CCl
Reactant: NC(=O)CS(=O)(=O)c1ccccc1Br
Product: CCN(CC)C(=O)CS(=O)(=O)c1ccccc1Br

Procedure:
The title compound was prepared in a manner similar to that described for 2-((2-bromophenyl)sulfonyl)acetamide using 2-chloro-N,N-diethylacetamide in Step A. 1H NMR (600 MHz, DMSO-d6) δ 8.01-7.97 (m, 1H), 7.91-7.87 (m, 1H), 7.66-7.60 (m, 2H), 4.75 (s, 2H), 3.47-3.39 (q, J=7.1, 2H), 3.25-3.14 (q, J=7.0, 2H), 1.18-1.09 (t, J=7.1, 3H), 0.99-0.87 (t, J=7.0, 3H).
Reaction SMILES: [CH3:1][N:2]1[CH:6]=[C:5]([C:7]2[CH:8]=[C:9]3[C:15]([C:16]4[N:21]=[C:20]([N:22]5[CH2:27][CH2:26][N:25]([C:28]([O:30][C:31]([CH3:34])([CH3:33])[CH3:32])=[O:29])[CH2:24][CH2:23]5)[CH:19]=[N:18][CH:17]=4)=[CH:14][N:13](S(C4C=CC=CC=4)(=O)=O)[C:10]3=[N:11][CH:12]=2)[CH:4]=[N:3]1.C(=O)([O-])[O-].[K+].[K+]>CO.C(Cl)Cl>[CH3:1][N:2]1[CH:6]=[C:5]([C:7]2[CH:8]=[C:9]3[C:15]([C:16]4[N:21]=[C:20]([N:22]5[CH2:23][CH2:24][N:25]([C:28]([O:30][C:31]([CH3:34])([CH3:33])[CH3:32])=[O:29])[CH2:26][CH2:27]5)[CH:19]=[N:18][CH:17]=4)=[CH:14][NH:13][C:10]3=[N:11][CH:12]=2)[CH:4]=[N:3]1
Reactant: Cn1cc(-c2cnc3c(c2)c(-c2cncc(N4CCN(C(=O)OC(C)(C)C)CC4)n2)cn3S(=O)(=O)c2ccccc2)cn1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: ClCCl
Solvent: CO
Product: Cn1cc(-c2cnc3[nH]cc(-c4cncc(N5CCN(C(=O)OC(C)(C)C)CC5)n4)c3c2)cn1
Temperature: 50 °C
Reaction time: 1 h

Procedure:
To a stirred solution of tert-butyl 4-{6-[5-(1-methyl-1H-pyrazol-4-yl)-1-(phenylsulfonyl)-1H-pyrrolo[2,3-b]pyridin-3-yl]pyrazin-2-yl}piperazine-1-carboxylate (0.077 g, 0.13 mmol) in MeOH (1.3 ml) was added potassium carbonate (0.053 g, 0.34 mmol). The reaction mixture was stirred at 50° C. for 1 hour, then at room temperature for 16 hours. The reaction mixture was diluted with MeOH (10 mL) and DCM (10 mL), silica gel was added, and concentrated to a crude residue. The crude residue was purified by silica gel chromatography (EtOAc/Hexanes gradient, followed by MeOH/DCM gradient) to afford tert-butyl 4-{6-[5-(1-methyl-1H-pyrazol-4-yl)-1H-pyrrolo[2,3-b]pyridin-3-yl]pyrazin-2-yl}piperazine-1-carboxylate as a white solid. LRMS calculated for C24H28N8O2 [M+H]+, 461.2; found 461.2.
Reaction SMILES: [N:1]1([CH2:7][CH2:8][N:9]([CH2:38][CH2:39][N:40]2[CH2:45][CH2:44][CH2:43][CH2:42][CH2:41]2)[C:10]2[C:23]3[O:22][CH2:21][CH2:20][N:19]4[C:15](=[C:16]([CH:32]5[CH2:37][CH2:36][CH2:35][CH2:34][CH2:33]5)[C:17]5[CH:27]=[CH:26][C:25]([C:28]([O:30]C)=[O:29])=[CH:24][C:18]=54)[C:14]=3[CH:13]=[CH:12][CH:11]=2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[OH-].[Na+].Cl>O1CCCC1.CO>[N:40]1([CH2:39][CH2:38][N:9]([CH2:8][CH2:7][N:1]2[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6]2)[C:10]2[C:23]3[O:22][CH2:21][CH2:20][N:19]4[C:15](=[C:16]([CH:32]5[CH2:37][CH2:36][CH2:35][CH2:34][CH2:33]5)[C:17]5[CH:27]=[CH:26][C:25]([C:28]([OH:30])=[O:29])=[CH:24][C:18]=54)[C:14]=3[CH:13]=[CH:12][CH:11]=2)[CH2:41][CH2:42][CH2:43][CH2:44][CH2:45]1
Reactant: COC(=O)c1ccc2c(C3CCCCC3)c3n(c2c1)CCOc1c-3cccc1N(CCN1CCCCC1)CCN1CCCCC1
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: C1CCOC1
Solvent: CO
Product: O=C(O)c1ccc2c(C3CCCCC3)c3n(c2c1)CCOc1c-3cccc1N(CCN1CCCCC1)CCN1CCCCC1
Temperature: 25 °C
Reaction time: 12 h

Procedure:
To a solution of methyl 4-{bis[2-(piperidin-1-yl)ethyl]amino}-12-cyclohexyl-6,7-dihydro-5-oxa-7a-azadibenzo[a,e]azulene-9-carboxylate (401 mg, 0.65 mmol) in tetrahydrofuran (4.0 ml) and methanol (4.0 ml) was added 4N aqueous sodium hydroxide solution (4.0 ml), and the mixture was stirred at room temperature for 12 hr. The reaction mixture was adjusted to pH 6 with 2N hydrochloric acid, and extracted with chloroform. The organic layer was washed with saturated brine and dried over anhydrous sodium sulfate. After filtration, the mixture was concentrated under reduced pressure, and ethyl acetate was added to the residue. The precipitated solid was collected by filtration to give 4-{bis[2-(piperidin-1-yl)ethyl]amino}-12-cyclohexyl-6,7-dihydro-5-oxa-7a-azadibenzo[a,e]azulene-9-carboxylic acid. To a solution of the obtained 4-{bis[2-(piperidin-1-yl)ethyl]amino}-12-cyclohexyl-6,7-dihydro-5-oxa-7a-azadibenzo[a,e]azulene-9-carboxylic acid in chloroform was added 4N HCl-ethyl acetate solution (4.0 ml). The reaction mixture was concentrated under reduced pressure and ethyl acetate was added. The precipitated solid was collected by filtration and dried in vacuo to give 4-{bis[2-(piperidin-1-yl)ethyl]amino}-12-cyclohexyl-6,7-dihydro-5-oxa-7a-azadibenzo[a,e]azulene-9-carboxylic acid trihydrochloride (338 mg, yield 73%).
Reaction SMILES: [OH:1][CH:2]1[CH2:5][N:4]([C:6]2[S:7][CH:8]=[C:9]([CH2:11][NH:12][C:13]([O:15][CH2:16][C:17]3[CH:22]=[CH:21][C:20]([N+:23]([O-:25])=[O:24])=[CH:19][CH:18]=3)=[O:14])[N:10]=2)[CH2:3]1.[CH3:26][S:27](Cl)(=[O:29])=[O:28].C(N(CC)CC)C>C(Cl)Cl>[CH3:26][S:27]([O:1][CH:2]1[CH2:3][N:4]([C:6]2[S:7][CH:8]=[C:9]([CH2:11][NH:12][C:13]([O:15][CH2:16][C:17]3[CH:22]=[CH:21][C:20]([N+:23]([O-:25])=[O:24])=[CH:19][CH:18]=3)=[O:14])[N:10]=2)[CH2:5]1)(=[O:29])=[O:28]
Reactant: O=C(NCc1csc(N2CC(O)C2)n1)OCc1ccc([N+](=O)[O-])cc1
Reactant: CS(=O)(=O)Cl
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: CS(=O)(=O)OC1CN(c2nc(CNC(=O)OCc3ccc([N+](=O)[O-])cc3)cs2)C1
Temperature: 25 °C
Reaction time: 2 h
Yield: 90.3 %

Procedure:
To a solution of 3-hydroxy-1-[4-(p-nitrobenzyloxycarbonylaminomethyl)-1,3-thiazol-2-yl]azetidine (457 mg, 1.25 mmol) (obtained as described in Reference Example 62(3)) in methylene chloride (25 ml) were added methanesulfonyl chloride (0.29 ml, 3.75 mmol) and triethylamine (0.53 ml, 3.80 mmol) in an ice bath. After stirring the mixture for 10 minutes in the ice bath, the resulting mixture was stirred at room temperature for 2 hours. After checking the completion of the reaction, the mixture was partitioned between ethyl acetate and saturated aqueous sodium hydrogencarbonate solution. The organic layer was washed with saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The residue was purified by chromatography on a silica gel column using toluene:acetonitrile (1:1) as the eluant to afford 3-methanesulfonyloxy-1-[4-(p-nitrobenzyloxycarbonylaminomethyl)-1,3-thiazol-2-yl)azetidine (499.4 mg, yield 90%) as a yellow solid.
Reaction SMILES: [Br:1][C:2]1[CH2:6][C:5]([CH2:9]O)([CH2:7]O)[CH2:4][C:3]=1[Br:11].[C:12]1([CH3:22])[CH:17]=[CH:16][C:15]([S:18](Cl)(=[O:20])=[O:19])=[CH:14][CH:13]=1>N1C=CC=CC=1>[Br:1][C:2]1[CH2:6][C:5]([CH2:9][S:18]([C:15]2[CH:16]=[CH:17][C:12]([CH3:22])=[CH:13][CH:14]=2)(=[O:20])=[O:19])([CH2:7][S:18]([C:15]2[CH:16]=[CH:17][C:12]([CH3:22])=[CH:13][CH:14]=2)(=[O:20])=[O:19])[CH2:4][C:3]=1[Br:11]
Reactant: OCC1(CO)CC(Br)=C(Br)C1
Reactant: Cc1ccc(S(=O)(=O)Cl)cc1
Solvent: c1ccncc1
Product: Cc1ccc(S(=O)(=O)CC2(CS(=O)(=O)c3ccc(C)cc3)CC(Br)=C(Br)C2)cc1
Reaction time: 8 h
Yield: 46.5 %

Procedure:
Under nitrogen, a stirred solution of 5.7 g (19.9 mmol) of 1,2-dibromo-4,4-di(hydroxymethyl)cyclopentene (Step 5) in 50 mL of pyridine at ambient temperature was treated with 19 g (99.7 mmol) of p-toluenesulfonyl chloride. The reaction was allowed to stir overnight and was concentrated in vacuo. The residue was dissolved ethyl acetate and washed twice with 3% hydrochloric acid followed by brine. The solution was dried (Na2SO4) and concentrated in vacuo to give 5.2 g (44%) of 1,2-dibromo-4,4-di(tosylmethyl)cyclopentene (14 in Synthetic Scheme V) as a colorless semisolid: NMR (CDCl3) d 2.42 (s, 4H), 2.47 (s, 6H), 3.90 (s, 4H), 7.37 (d, J=8 Hz, 4H), 7.74 (d, J=8 Hz, 4H).
Reaction SMILES: [OH-].[K+].[CH:3]1([O:8][C:9]2[C:14]([O:15][CH3:16])=[CH:13][N:12]=[C:11]([C:17]([O:19]C)=[O:18])[CH:10]=2)[CH2:7][CH2:6][CH2:5][CH2:4]1>O.CO>[CH:3]1([O:8][C:9]2[C:14]([O:15][CH3:16])=[CH:13][N:12]=[C:11]([C:17]([OH:19])=[O:18])[CH:10]=2)[CH2:4][CH2:5][CH2:6][CH2:7]1
Reactant: COC(=O)c1cc(OC2CCCC2)c(OC)cn1
Agent: [K+]
Agent: [OH-]
Solvent: O
Solvent: CO
Product: COc1cnc(C(=O)O)cc1OC1CCCC1
Reaction time: 45 h
Yield: 36.2 %

Procedure:
A solution of potassium hydroxide (4.71 g) in water (32 mL) is added to a solution of methyl 4-cyclopentyloxy-5-methoxypyridine-2-carboxylate (7.03 g) in methanol (188 mL) and the mixture allowed to stand for 45 hours. After concentrating in vacuo the residue is dissolved in water, washed with ethyl acetate and basefied to pH 5 with concentrated aqueous hydrochloric acid. The mixture is extracted with dichloromethane, the extracts dried (MgSO4) and evaporated to give 4-cyclopentyloxy-5-methoxypyridine-2-carboxylic acid (2.4 g) as a white solid.
Reaction SMILES: [C:1]([OH:7])(=O)/[C:2](=[CH:4]/[CH3:5])/[CH3:3].C(Cl)(=O)C(Cl)=O.[NH2:14][C:15]1[CH:36]=[CH:35][C:18]([CH2:19][NH:20]/[CH:21]=[C:22]2\[C:23](=[O:34])[NH:24][C:25](=[O:33])[C:26]3[C:31]\2=[CH:30][C:29]([I:32])=[CH:28][CH:27]=3)=[CH:17][C:16]=1[O:37][Si](C(C)C)(C(C)C)C(C)C.C(N(C(C)C)CC)(C)C.[F-].C([N+](CCCC)(CCCC)CCCC)CCC>C(#N)C.O1CCCC1>[OH:37][C:16]1[CH:17]=[C:18]([CH2:19][NH:20]/[CH:21]=[C:22]2\[C:23](=[O:34])[NH:24][C:25](=[O:33])[C:26]3[C:31]\2=[CH:30][C:29]([I:32])=[CH:28][CH:27]=3)[CH:35]=[CH:36][C:15]=1[NH:14][C:1](=[O:7])/[C:2](/[CH3:3])=[CH:4]/[CH3:5]
Reactant: C/C=C(\C)C(=O)O
Reactant: CC(C)[Si](Oc1cc(CN/C=C2\C(=O)NC(=O)c3ccc(I)cc32)ccc1N)(C(C)C)C(C)C
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: O=C(Cl)C(=O)Cl
Agent: [F-]
Solvent: CC#N
Solvent: CCN(C(C)C)C(C)C
Solvent: C1CCOC1
Product: C/C=C(\C)C(=O)Nc1ccc(CN/C=C2\C(=O)NC(=O)c3ccc(I)cc32)cc1O
Temperature: 65 °C
Reaction time: 0.5 h
Yield: 21.1 %

Procedure:
To a suspension or solution of carboxylic acid, in this case tiglic acid (0.11 g, 1.1 mmol) in anhydrous acetonitrile (3 mL) is added oxalyl chloride (neat, 100 μL, 1.1 mmol). The mixture is shaken at 65° C. for 30 minutes and then reduced to half volume under reduced pressure. The resulting acetonitrile solution is then added to a solution of (4Z)-4-[({4-amino-3-[(triisopropylsilyl)oxy]benzyl}amino)methylene]-6-iodoisoquinoline-1,3(2H,4H)-dione (65 mg, 0.11 mmol) and diisopropylethylamine (380 μL, 2.2 mmol) in tetrahydrofuran (3 mL) After stirring overnight at room temperature, the reaction mixture is concentrated to dryness under reduced pressure. Tetrabutylammonium fluoride solution (1.0 M, 2.0 mL, 2.0 mmol) is added and the mixture is shaken at 55° C. for 2 hours and then allowed to cool to room temperature. Following concentration, the residue is triturated with water and the resulting solid collected by filtration, washed with acetonitrile, and dried under house vacuum to give (2E)-N-[2-hydroxy-4-({[(Z)-(6-iodo-1,3-dioxo-2,3-dihydroisoquinolin-4(1H)-ylidene)methyl]amino}methyl)phenyl]-2-methylbut-2-enamide (12 mg, 21%).
Reaction SMILES: [C:1]1([P:7]([C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[C:8]2[CH:16]=[CH:15][CH:14]=[CH:13][C:9]=2[C:10](O)=[O:11])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[CH2:23]([SH:25])[CH3:24].CC(C)N=C=NC(C)C>CN(C1C=CN=CC=1)C.C(Cl)Cl>[C:17]1([P:7]([C:1]2[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=2)[C:8]2[CH:16]=[CH:15][CH:14]=[CH:13][C:9]=2[C:10]([S:25][CH2:23][CH3:24])=[O:11])[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1
Reactant: O=C(O)c1ccccc1P(c1ccccc1)c1ccccc1
Reactant: CCS
Agent: CC(C)N=C=NC(C)C
Agent: CN(C)c1ccncc1
Solvent: ClCCl
Product: CCSC(=O)c1ccccc1P(c1ccccc1)c1ccccc1
Temperature: 0 °C
Reaction time: 8 h
Yield: 74.8 %

Procedure:
2-(Diphenylphosphanyl)benzoic acid (0.50 g, 1.63 mmol) and DMAP (20 mg, 0.163 mmol) were dissolved in CH2Cl2 (10 mL). Ethanethiol (EtSH, 0.35 mL, 4.89 mmol) was added, and the solution was placed under Ar(g) and cooled to 0° C. DIC (0.25 mL, 1.63 mmol) was added dropwise, and the resulting solution was allowed to warm to room temperature and stirred overnight. The solution was then filtered, and the filtrate was concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography, eluting with 10% EtOAc/hexanes, to give phosphine 1b as a pale yellow solid (0.43 g, 1.22 mmol, 75% yield).
Reaction SMILES: O[CH2:2][CH2:3][CH2:4][C:5]1[CH:10]=[CH:9][C:8]([OH:11])=[CH:7][C:6]=1[OH:12].C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1CCN(C(N=NC(N2CCCCC2)=O)=O)CC1>C1COCC1>[O:12]1[C:6]2[C:5](=[CH:10][CH:9]=[C:8]([OH:11])[CH:7]=2)[CH2:4][CH2:3][CH2:2]1
Reactant: OCCCc1ccc(O)cc1O
Agent: O=C(N=NC(=O)N1CCCCC1)N1CCCCC1
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: C1CCOC1
Product: Oc1ccc2c(c1)OCCC2
Temperature: 25 °C
Reaction time: 17 h
Yield: 66.2 %

Procedure:
To a stirred solution of 4-(3-Hydroxy-propyl)-benzene-1,3-diol (3.05 g, 18.1 mmol, from Step 1) in anhydrous THF (50 mL) were added Ph3P (7.13 g, 27.2 mmol, 1.5 eq) and ADDP (6.86 g, 27.2 mmol, 1.5 eq) under argon. The mixture was stirred at rt for 17 h. The white solid was filtered off and the solvent was removed from the filtrate. The residue was purified on silica gel (flash column chromatography) eluting with 5% ethyl acetate-hexane followed by 20% ethyl acetate-hexane to provide the desired product as white solid (1.80 g, 60.5%). 1H-NMR (CD3CN) δ 6.87 (d, 1H), 6.70 (broad, s, 1H, OH), 6.31 (dd, J=2.4, 8.2 Hz, 1H), 6.20 (d, 1H), 4.12 (t, 2H), 2.69 (t, 2H), 1.95 (m, 2H).
Reaction SMILES: O=[C:2]1[C:10]2([CH2:15][CH2:14][CH2:13][CH2:12][CH2:11]2)[C:9]2[C:4](=[CH:5][CH:6]=[C:7]([C:16]3[N:20]([CH3:21])[C:19]([C:22]#[N:23])=[CH:18][CH:17]=3)[CH:8]=2)[NH:3]1.COC1C=CC(P2(SP(C3C=CC(OC)=CC=3)(=S)S2)=[S:33])=CC=1.O>C1(C)C=CC=CC=1>[S:33]=[C:2]1[C:10]2([CH2:15][CH2:14][CH2:13][CH2:12][CH2:11]2)[C:9]2[C:4](=[CH:5][CH:6]=[C:7]([C:16]3[N:20]([CH3:21])[C:19]([C:22]#[N:23])=[CH:18][CH:17]=3)[CH:8]=2)[NH:3]1
Reactant: Cn1c(C#N)ccc1-c1ccc2c(c1)C1(CCCCC1)C(=O)N2
Reactant: COc1ccc(P2(=S)SP(=S)(c3ccc(OC)cc3)S2)cc1
Solvent: Cc1ccccc1
Solvent: O
Product: Cn1c(C#N)ccc1-c1ccc2c(c1)C1(CCCCC1)C(=S)N2
Temperature: 80 °C
Yield: 90.5 %

Procedure:
To a solution of 5-(2′-oxospiro[cyclohexane-1,3′-[3H]indol]-5′-yl)-1-methyl-pyrrole-2-carbonitrile (0.55 g, 1.8 mmol, 1 eq) in toluene (50 mL) was added Lawesson's reagent (0.47 g, 1.1 mmol, 0.65 eq) and the reaction was heated to 80° C. for 1 hour. The reaction was cooled to room temperature, poured into water (100 mL) and extracted with ethyl acetate (2×100 mL). The organic layers were combined, washed with brine (50 mL), dried over magnesium sulfate, filtered and concentrated in vacuo. Purification by flash column chromatography on silica gel gave the product as a white solid (0.32 g, 55%). 1H NMR (d6-DMSO, 500 MHz) δ 1.36-1.99 (m, 10H), 3.7 (s, 3H), 6.35 (d, 1H, J=4.2 Hz), 7.05 (d, 1H, J=4.2 Hz), 7.16 (d, 1H, J=7.9 Hz), 7.44 (dd, 1H, J=1.6, 8.1 Hz), 7.83 (d, 1H, J=1.6 Hz), 12.75 (s, 1H). MS (ESI) [M−H]−=320. Anal. calcd. for C19H19N3S: C, 70.99; H, 5.96; N, 13.07. Found: C, 68.69; H, 5.36; N, 12.27.
Reaction SMILES: B(F)(F)F.CCOCC.[CH2:10]([O:17][C:18]1[CH:36]=[CH:35][C:21]([C:22]([O:24][CH2:25][C:26]([C:28]2[CH:33]=[CH:32][C:31]([Br:34])=[CH:30][CH:29]=2)=O)=O)=[CH:20][CH:19]=1)[CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH3:16].C([NH2:40])(=O)C>C(Cl)Cl>[Br:34][C:31]1[CH:32]=[CH:33][C:28]([C:26]2[N:40]=[C:22]([C:21]3[CH:35]=[CH:36][C:18]([O:17][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH3:16])=[CH:19][CH:20]=3)[O:24][CH:25]=2)=[CH:29][CH:30]=1
Reactant: CCCCCCCOc1ccc(C(=O)OCC(=O)c2ccc(Br)cc2)cc1
Reactant: CC(N)=O
Agent: FB(F)F
Solvent: ClCCl
Solvent: CCOCC
Product: CCCCCCCOc1ccc(-c2nc(-c3ccc(Br)cc3)co2)cc1
Temperature: 50 °C
Reaction time: 16 h
Yield: 28.6 %

Procedure:
To boron trifluoride etherate (0.322 mL, 2.5 mmol) was added 2-(4-bromophenyl)-2-oxoethyl 4-(heptyloxy)benzoate (1.0 g, 2.3 mmol) and acetamide (4.91 g, 83.0 mmol) in DCM (10 mL). The reaction mixture was heated to 50° C. then 140° C. for 16 h, DCM was distilled off. The reaction mixture was cooled, diluted with acetonitrile and stirred at RT for 1 h. The precipitate was isolated by filtration to afford 273 mg (23%) of 4-(4-bromophenyl)-2-(4-(heptyloxy)phenyl)oxazole as a brown solid. LCMS-ESI (m/z) calculated for C22H24BrNO2: 414.3; found 414.0 [M+H]+, tR=3.00 min. (Method 4).
Reaction SMILES: Br[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9]Br.[OH:11][C:12]1[CH:19]=[CH:18][C:15](C=O)=[CH:14][CH:13]=1.[C:20](=O)([O-])[O-:21].[K+].[K+].O>CN(C=O)C>[CH:20]([CH:5]([CH2:6][CH2:7][CH2:8][CH3:9])[CH2:4][CH2:3][CH2:2][O:11][C:12]1[CH:19]=[CH:18][CH:15]=[CH:14][CH:13]=1)=[O:21]
Reactant: O=Cc1ccc(O)cc1
Reactant: BrCCCCCCCCBr
Reactant: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CN(C)C=O
Product: CCCCC(C=O)CCCOc1ccccc1
Temperature: 55 °C
Reaction time: 8 h
Yield: 549.1 %

Procedure:
A mixture of 1,8-dibromooctane (8.0 g, 29.5 mmol), p-hydroxy-benzaldehyde (7.2 g, 59 mmol) and potassium carbonate (8.2 g, 6.0 mmol) in DMF (50 ml) was heated to 55° C. with stirring for 8 h. The cooled solution was poured into water and the precipitate was filtered, washed with water, and dried. Recrystallisation from hot ethanol (200 ml) yielded (15) (7.72 g, 73%), m.p. 89° C.-91° C., (Found C. 74.4, H 7.4 %. C22H26O4 requires C 74.5, H 7.4 %), 1H NMR (250.1 MHz, CDCl3) δ: 1.3-1.9(12H, m, alkyl), 4.02(4H, t, J=7 Hz, CH2O), 6.97 and 7.81 (8H, 2 d, J=11 Hz, aromatic), 9.85 (2H, s, CHO); IR (KBr) vmax /cm-1 1698 s, 1598 s, 1156 s, 834 s. m/z 354 (M, 45), 326 (30), 233 (15), 121 (55), 69 (100).
Reaction SMILES: C1(C)C=CC(=[C:7]2[CH:12]3[C:13]([CH3:15])([CH3:14])[C:9]([CH3:16])([CH2:10][CH2:11]3)[C:8]2=[O:17])CC=1.[OH:19][S:20]([OH:23])(=O)=[O:21].O=S(=O)=O.[Cl-].[Na+:29]>>[CH3:16][C:9]1[CH:10]=[CH:11][C:12]([CH:13]=[C:7]2[CH:12]3[C:13]([CH3:15])([CH3:14])[C:9]([CH3:16])([CH2:10][CH2:11]3)[C:8]2=[O:17])=[CH:7][C:8]=1[S:20]([O-:23])(=[O:21])=[O:19].[Na+:29]
Reactant: O=S(=O)(O)O
Reactant: CC1=CCC(=C2C(=O)C3(C)CCC2C3(C)C)C=C1
Agent: O=S(=O)=O
Agent: [Cl-]
Agent: [Na+]
Product: Cc1ccc(C=C2C(=O)C3(C)CCC2C3(C)C)cc1S(=O)(=O)[O-]

Procedure:
25.4 g of 3-p-tolylidene camphor are added to 64 ml of oleum containing 10% SO3, with cooling so as to keep the temperature of the reaction mixture around 35° C. The resulting mixture is then poured into 150 ml of a saturated sodium chloride solution, the mixture being cooled to below 25° C. A precipitate is obtained which is filtered and then washed with a saturated sodium chloride solution. The wet product is made into paste in 70 ml of water. It is then filtered and recrystallized in an 80:20 water-acetone mixture. Thus, 29.3 g of a white powder, melting at 240° C. are obtained.