Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH:1]1[C:9]2[C:8]3[CH:10]=[CH:11][CH:12]=[CH:13][C:7]=3[S:6][C:5]=2[C:4]([C:14]2[C:23]3[C:18](=[CH:19][C:20]([C:24]4[C:29]5[S:30][C:31]6[CH:36]=[CH:35][CH:34]=[CH:33][C:32]=6[C:28]=5[CH:27]=[CH:26][CH:25]=4)=[CH:21][CH:22]=3)[CH:17]=[CH:16][C:15]=2[OH:37])=[CH:3][CH:2]=1.[CH2:38]1C[O:41][CH2:40][CH2:39]1.C(N(CC)CC)C.C(Cl)(=O)C=C>O.C(OCC)(=O)C>[C:40]([O:37][C:15]1[CH:16]=[CH:17][C:18]2[C:23](=[CH:22][CH:21]=[C:20]([C:24]3[C:29]4[S:30][C:31]5[CH:36]=[CH:35][CH:34]=[CH:33][C:32]=5[C:28]=4[CH:27]=[CH:26][CH:25]=3)[CH:19]=2)[C:14]=1[C:4]1[C:5]2[S:6][C:7]3[CH:13]=[CH:12][CH:11]=[CH:10][C:8]=3[C:9]=2[CH:1]=[CH:2][CH:3]=1)(=[O:41])[CH:39]=[CH2:38]
Reactant: C1CCOC1
Reactant: Oc1ccc2cc(-c3cccc4c3sc3ccccc34)ccc2c1-c1cccc2c1sc1ccccc12
Agent: C=CC(=O)Cl
Solvent: O
Solvent: CCOC(C)=O
Solvent: CCN(CC)CC
Product: C=CC(=O)Oc1ccc2cc(-c3cccc4c3sc3ccccc34)ccc2c1-c1cccc2c1sc1ccccc12
Reaction time: 0.5 h
Yield: 90 %

Procedure:
1.8 g of the thus obtained 1,6-bis(4-dibenzothiophenyl)-2-naphthol is placed in a round bottom flask; 30 mL of THF is added to form a transparent solution; after ice cooling the flask, 0.58 g of triethylamine is added; 0.48 g of acryloyl chloride is then added dropwise; after adding the whole, the temperature is returned to room temperature; and the mixture is stirred for 30 minutes. 15 mL of water is added; the mixture is vigorously stirred; and 30 mL of ethyl acetate and 15 mL of saturated salt water are then added, thereby separating an aqueous solution. An organic phase is washed with saturated salt water and dried upon application of magnesium sulfate. The resulting mixture is concentrated by filtration with a filter paper; and a major product is separated by a silica gel column (eluate: hexane/dichloromethane mixture), thereby obtaining 1.8 g (yield: 90%) of the foregoing white solid. 1H NMR (CDCl3, 400 MHz): δ (ppm) 5.66 (dd=1.2 & 10.4 Hz, 1H), 5.94 (dd=10.4 & 17.2 Hz, 1H), 6.18 (dd=1.2 & 17.2 Hz, 1H), 7.37 to 7.60 (m, 10H), 7.67 to 7.74 (m, 2H), 7.77 to 7.82 (m, 1H), 8.07 (d=8.8 Hz, 1H), 8.10 to 8.24 (m, 4H), 8.15 (d=1.6 Hz, 1H)
Reaction SMILES: [F:1][C:2]([F:9])([CH3:8])/[CH:3]=[CH:4]/[C:5]([OH:7])=O.C(Cl)(=O)C(Cl)=O.Cl.Cl.Cl.[CH3:19][C:20]1[CH:25]=CN=[C:22]([N:26]2[CH2:30][CH2:29][C@H:28]([NH2:31])[CH2:27]2)[CH:21]=1.[CH2:32]([N:34](C(C)C)C(C)C)C>ClCCl.CN(C=O)C>[F:9][C:2]([F:1])([CH3:8])/[CH:3]=[CH:4]/[C:5]([NH:31][C@H:28]1[CH2:29][CH2:30][N:26]([C:22]2[CH:32]=[N:34][CH:25]=[C:20]([CH3:19])[CH:21]=2)[CH2:27]1)=[O:7]
Reactant: CC(F)(F)/C=C/C(=O)O
Reactant: CCN(C(C)C)C(C)C
Reactant: Cc1ccnc(N2CC[C@H](N)C2)c1
Agent: Cl
Agent: O=C(Cl)C(=O)Cl
Solvent: CN(C)C=O
Solvent: ClCCl
Product: Cc1cncc(N2CC[C@H](NC(=O)/C=C/C(C)(F)F)C2)c1
Temperature: 25 °C
Reaction time: 0.25 h
Yield: 67 %

Procedure:
(E)-4,4-Difluoropent-2-enoic acid (22 mg, 0.16 mmol) was dissolved in dichloromethane (1 ml), oxalyl chloride (14 μl, 0.16 mol) and one drop of DMF were added and the resulting solution was stirred at room temperature for 15 minutes. This solution was added to a solution of (3S)-1-(4-methyl-2-pyridyl)pyrrolidin-3-amine trihydrochloride (29 mg, 0.1 mmol) in DCM (2 ml). Ethyl-N,N-diisopropylamine (DIPEA, 70 μl, 0.4 mmol) was added and the resulting mixture was stirred at room temperature overnight. The mixture was concentrated under reduced pressure and the resulting residue was purified by preparative HPLC (Waters XBridge, gradient of water containing 0.1% NH3 and acetonitrile) to yield 20 mg of a solid (0.067 mmol, 67%).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][CH:12]=1)[C:9](=[O:13])[CH2:8][CH2:7][CH2:6]2.[Br:14][C:15]1[CH:16]=[N:17][CH:18]=[CH:19][C:20]=1[CH:21]=O>>[Br:14][C:15]1[CH:16]=[N:17][CH:18]=[CH:19][C:20]=1/[CH:21]=[C:8]1/[C:9](=[O:13])[C:10]2[C:5]([CH2:6][CH2:7]/1)=[CH:4][C:3]([O:2][CH3:1])=[CH:12][CH:11]=2
Reactant: O=Cc1ccncc1Br
Reactant: COc1ccc2c(c1)CCCC2=O
Product: COc1ccc2c(c1)CC/C(=C\c1ccncc1Br)C2=O

Procedure:
The title compound 87 is prepared according to the procedure reported in Example 34.2 with 6-methoxy-1-tetralone (4.74 g, 26.9 mmol) and 3-bromo-4-pyridinecarboxaldehyde (5.0 g, 26.9 mmol) as reactants. White solid. (Yield 7.0 g, 76%).
Reaction SMILES: [C:1](Cl)(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[Cl-].[Al+3].[Cl-].[Cl-].[Cl:14][C:15]1[CH:16]=[C:17]2[C:21](=[CH:22][CH:23]=1)[NH:20][C:19](=[O:24])[CH2:18]2>CO>[C:1]([C:22]1[CH:23]=[C:15]([Cl:14])[CH:16]=[C:17]2[C:21]=1[NH:20][C:19](=[O:24])[CH2:18]2)(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: O=C(Cl)c1ccccc1
Reactant: O=C1Cc2cc(Cl)ccc2N1
Agent: [Al+3]
Agent: [Cl-]
Solvent: CO
Product: O=C1Cc2cc(Cl)cc(C(=O)c3ccccc3)c2N1

Procedure:
A mixture of 162.5 g. (1.08 mole) of benzoyl chloride and 260 g. of aluminum chloride (1.80 mole) heated to 200°C. with stirring was treated with 65 g. (0.360 mole) of recrystallized 5-chloroindolin-2-one. This mixture was stirred 15 min. and poured over ice. The resulting precipitate was triturated with boiling water and then chloroform. The chloroform solution was washed with 5% sodium bicarbonate, water, dried over sodium sulfate, and stripped to yield approximately 55 g. of a glossy solid. This material was then triturated with hot methanol and the methanol evaporated under vacuum to yield approximately 20 g. of a solid yellow material. Extraction of a benzene solution of this material with conc. hydrochloric acid removed unreacted 5-chloroindolin-2-one and the benzene solution after washing with water and drying yielded on evaporation 3 g. of a blue-gray material. Trituration of this material with room temperature methanol gave a residue which on recrystallization from methanol yielded 2.5 g. of a tan solid identified as product, m.p. 186°-187°C.
Reaction SMILES: [CH3:1][C:2]1[CH:3]=[C:4]([CH:7]=[CH:8][C:9]=1[CH3:10])[CH2:5][NH2:6].[C:11](Cl)(Cl)=[O:12].CCN(C(C)C)C(C)C.[NH2:24][C:25]1[CH:34]=[CH:33][CH:32]=[C:31]2[C:26]=1[CH:27]=[C:28]([CH3:35])[N:29]=[CH:30]2>C1(C)C=CC=CC=1>[CH3:1][C:2]1[CH:3]=[C:4]([CH:7]=[CH:8][C:9]=1[CH3:10])[CH2:5][NH:6][C:11]([NH:24][C:25]1[CH:34]=[CH:33][CH:32]=[C:31]2[C:26]=1[CH:27]=[C:28]([CH3:35])[N:29]=[CH:30]2)=[O:12]
Reactant: Cc1ccc(CN)cc1C
Reactant: O=C(Cl)Cl
Reactant: Cc1cc2c(N)cccc2cn1
Solvent: CCN(C(C)C)C(C)C
Solvent: Cc1ccccc1
Product: Cc1cc2c(NC(=O)NCc3ccc(C)c(C)c3)cccc2cn1
Temperature: 25 °C
Reaction time: 2 h

Procedure:
3,4-Dimethylbenzylamine (0.3 mL, 2.1 mmol) in toluene (11 mL) was added carefully to a 20% w/v solution of phosgene in toluene (4.5 mL). The mixture was refluxed overnight and was then concentrated in vacuo. The residue was then taken up in toluene (10 mL) and treated with DIEA (1.5 mL, 8.63 mmol) and 5-amino-3-methylisoquinoline (155 mg, 1.08 mmol). The reaction mixture was stirred at 80° for 2 h and was then cooled to room temperature. The precipitated solid was collected by filtration and was chromatographed on silica gel (97:3 CH2Cl2—CH3OH to 9:1 CH2Cl2—CH3OH, eluant gradient) to afford the desired product, A-473191. Treatment of this solid with methanolic HCl yielded the corresponding hydrochloride salt. 1H NMR (300 MHz, DMSO-d6) δ 9.16 (s, 1H), 8.59 (s, 1H), 8.24 (d, 1H, J=7.8 Hz), 7.74 (s, 1H), 7.68 (d, 1H, J=8.2 Hz), 7.50 (t, 1H, J=7.9 Hz), 7.08-7.12 (m, 3H), 6.95 (m, 1H), 4.28 (d, 2H, 5.8 Hz), 2.64 (s, 3H), 2.22 (s, 3H), 2.20 (s, 3H); MS (ESI+) m/z 320 (M+H).
Reaction SMILES: [Br:1][C:2]1[CH:10]=[CH:9][CH:8]=[C:7]2[C:3]=1[CH:4]=[CH:5][N:6]2[C:11]1[CH:16]=[CH:15][N:14]=[C:13]([S:17][CH3:18])[N:12]=1.C1C=C(Cl)C=C(C(OO)=[O:27])C=1.CCOC(C)=O.CCCCCC>C(Cl)Cl>[Br:1][C:2]1[CH:10]=[CH:9][CH:8]=[C:7]2[C:3]=1[CH:4]=[CH:5][N:6]2[C:11]1[CH:16]=[CH:15][N:14]=[C:13]([S:17]([CH3:18])=[O:27])[N:12]=1
Reactant: O=C(OO)c1cccc(Cl)c1
Reactant: CSc1nccc(-n2ccc3c(Br)cccc32)n1
Solvent: CCOC(C)=O
Solvent: CCCCCC
Solvent: ClCCl
Product: CS(=O)c1nccc(-n2ccc3c(Br)cccc32)n1
Temperature: 0 °C
Reaction time: 1 h
Yield: 94.9 %

Procedure:
To a solution of 4-bromo-1-(2-methylsulfanyl-pyrimidin-4-yl)-1H-indole (5.0 g) in DCM (200 mL) at 0° C. was added MCPBA (4.01 g) in portions, and the mixture stirred at 0° C. for 1 h. The reaction mixture was quenched in 10% Na2SO3 (aq), partitioned between DCM and NaHCO3 (aq), the organic layer washed with NaHCO3 (aq), and dried over Na2SO4. The solvent was stripped to provide a light yellow solid, which was then treated with hot EtOAc/hexane (50:50), filtered, dried to provide 4-bromo-1-(2-methylsulfinyl-pyrimidin-4-yl)-1H-indole (4.98 g) as an off-white powder.
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:13]=[CH:12][N:11]=[CH:10][C:9]=2[N:14]([CH3:28])[C:15](=[O:27])[C:16]2[CH:21]=[C:20]([C:22]([F:25])([F:24])[F:23])[CH:19]=[C:18]([SH:26])[CH:17]=2)=[C:4]([O:29][CH3:30])[CH:3]=1.Br[CH2:32][CH2:33][NH:34][C:35](=[O:41])[O:36][C:37]([CH3:40])([CH3:39])[CH3:38].CCN(C(C)C)C(C)C.[NH4+].[Cl-]>C(#N)C.CCOC(C)=O>[C:37]([O:36][C:35](=[O:41])[NH:34][CH2:33][CH2:32][S:26][C:18]1[CH:19]=[C:20]([C:22]([F:25])([F:24])[F:23])[CH:21]=[C:16]([C:15](=[O:27])[N:14]([C:9]2[CH:10]=[N:11][CH:12]=[CH:13][C:8]=2[C:5]2[CH:6]=[CH:7][C:2]([F:1])=[CH:3][C:4]=2[O:29][CH3:30])[CH3:28])[CH:17]=1)([CH3:40])([CH3:39])[CH3:38]
Reactant: CC(C)(C)OC(=O)NCCBr
Reactant: COc1cc(F)ccc1-c1ccncc1N(C)C(=O)c1cc(S)cc(C(F)(F)F)c1
Agent: [Cl-]
Agent: [NH4+]
Solvent: CCOC(C)=O
Solvent: CC#N
Solvent: CCN(C(C)C)C(C)C
Product: COc1cc(F)ccc1-c1ccncc1N(C)C(=O)c1cc(SCCNC(=O)OC(C)(C)C)cc(C(F)(F)F)c1
Temperature: 25 °C
Reaction time: 3 h

Procedure:
To a suspension of N-(4-(4-fluoro-2-methoxyphenyl)pyridin-3-yl)-3-mercapto-N-methyl-5-(trifluoromethyl)benzamide (0.1 g, 229 μmol, example 216, intermediate a) in acetonitrile (2 mL) were added tert-butyl 2-bromoethylcarbamate (56.5 mg, 252 μmol) and DIPEA (59.2 mg, 80.0 μL, 458 μmol). After the addition of DIPEA the white suspension turned to a yellow solution, which was stirred at room temperature for 3 hours. The reaction mixture was poured on saturated aqueous NH4Cl solution and EtOAc and the layers were separated. The aqueous layer was extracted twice with EtOAc. The organic layers were dried over MgSO4, filtered, treated with silica gel and evaporated. The compound was purified by silica gel chromatography on a 10 g column using an MPLC system eluting with a gradient of n-heptane:EtOAc (100:0 to 0:100). Colorless foam (0.111 g; 83%). MS (ESI): m/z=580.19 [M+H]+.
Reaction SMILES: [C:1]([C:6]1[N:10]2[C:11]([CH2:15]Cl)=[CH:12][CH:13]=[CH:14][C:9]2=[N:8][CH:7]=1)([O:3]CC)=O.[C:17]([O:21][C:22]([N:24]1[CH2:29][CH2:28][CH:27]([CH2:30][NH2:31])[CH2:26][CH2:25]1)=[O:23])([CH3:20])([CH3:19])[CH3:18].C(N(CC)CC)C>C(O)C>[C:17]([O:21][C:22]([N:24]1[CH2:29][CH2:28][CH:27]([CH2:30][N:31]2[CH2:15][C:11]3[N:10]4[C:6](=[CH:7][N:8]=[C:9]4[CH:14]=[CH:13][CH:12]=3)[C:1]2=[O:3])[CH2:26][CH2:25]1)=[O:23])([CH3:20])([CH3:19])[CH3:18]
Reactant: CC(C)(C)OC(=O)N1CCC(CN)CC1
Reactant: CCOC(=O)c1cnc2cccc(CCl)n12
Solvent: CCO
Solvent: CCN(CC)CC
Product: CC(C)(C)OC(=O)N1CCC(CN2Cc3cccc4ncc(n34)C2=O)CC1
Yield: 72.5 %

Procedure:
A solution prepared by dissolving 5.78 g (24.22 mM) of 3-carbethoxy-5-chloromethylimidazo[1,2-a]pyridine, 7.78 g (36.33 mM) of 1-tert-butoxycarbonyl-4-aminomethylpiperidine, and 6.75 ml (48.44 mM) of triethylamine in 100 ml of ethanol was refluxed under argon gas for 3 hours. After completion of the reaction, the solvent was distilled off under reduced pressure and the residue was extracted with 100 ml of chloroform. The organic layer was washed with saturated aqueous NaCl solution and dried over MgSO4 and the solvent was distilled off under reduced pressure. The residue was purified by silica gel column chromatography (eluent: chloroform-methanol=20:1) to provide 6.50 g (yield 72.4%) of the title compound as yellow liquid.
Reaction SMILES: [OH:1][C:2]1[C:7]2[CH:8]=[C:9]([CH3:11])[O:10][C:6]=2[CH:5]=[C:4]([C:12]([O:14]CC)=O)[CH:3]=1.[F:17][C:18]1[CH:28]=[C:27](F)[CH:26]=[CH:25][C:19]=1[C:20]([N:22]([CH3:24])[CH3:23])=[O:21].[NH2:30][C:31]1[CH:36]=[CH:35][C:34]([CH3:37])=[CH:33][N:32]=1>>[CH3:23][N:22]([CH3:24])[C:20]([C:19]1[CH:25]=[CH:26][C:27]([O:1][C:2]2[C:7]3[CH:8]=[C:9]([CH3:11])[O:10][C:6]=3[CH:5]=[C:4]([C:12]([NH:30][C:31]3[CH:36]=[CH:35][C:34]([CH3:37])=[CH:33][N:32]=3)=[O:14])[CH:3]=2)=[CH:28][C:18]=1[F:17])=[O:21]
Reactant: CN(C)C(=O)c1ccc(F)cc1F
Reactant: CCOC(=O)c1cc(O)c2cc(C)oc2c1
Reactant: Cc1ccc(N)nc1
Product: Cc1ccc(NC(=O)c2cc(Oc3ccc(C(=O)N(C)C)c(F)c3)c3cc(C)oc3c2)nc1

Procedure:
The title compound was prepared in a similar manner as described for Example 271, from ethyl 4-hydroxy-2-methylbenzofuran-6-carboxylate (0.275 g, 1.25 mmol), 2,4-difluoro-N,N-dimethylbenzamide (0.289 g, 1.56 mmol) and 2-amino-5-methylpyridine (0.229 g, 2.1 mmol) in two steps to give an off-white solid (131 mg, 24% yield). 1H NMR (400 MHz, DMSO-d6) δ 10.79 (s, 1 H) 8.21 (m, 1 H) 8.16 (s, 1 H) 8.06-8.08 (d, 1 H)) 7.66 (m, 1 H) 7.64 (m, 1 H) 7.37-7.41 (t, 1 H) 7.02-7.06 (m, 1 H) 6.89-6.92 (m, 1 H) 6.50 (s, 1 H) 2.99 (s, 3 H) 2.87 (m, 3 H) 2.47 (m, 3 H) 2.27 (s, 3 H).
Reaction SMILES: C([O:3][C:4](=[O:26])[C:5]1[CH:10]=[CH:9][C:8]([O:11][CH:12]([CH3:14])[CH3:13])=[C:7]([O:15][CH2:16][CH2:17][C:18]2[CH:23]=[CH:22][C:21]([Cl:24])=[CH:20][C:19]=2[Cl:25])[CH:6]=1)C.O.[OH-].[Na+].Cl>O1CCOCC1>[Cl:25][C:19]1[CH:20]=[C:21]([Cl:24])[CH:22]=[CH:23][C:18]=1[CH2:17][CH2:16][O:15][C:7]1[CH:6]=[C:5]([CH:10]=[CH:9][C:8]=1[O:11][CH:12]([CH3:14])[CH3:13])[C:4]([OH:26])=[O:3]
Reactant: CCOC(=O)c1ccc(OC(C)C)c(OCCc2ccc(Cl)cc2Cl)c1
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: O
Solvent: C1COCCO1
Product: CC(C)Oc1ccc(C(=O)O)cc1OCCc1ccc(Cl)cc1Cl
Temperature: 60 °C
Reaction time: 16 h

Procedure:
0.75 g (1.89 mmol) of 3-[2-(2,4-Dichloro-phenyl)-ethoxy]-4-isopropoxy-benzoic acid ethyl ester was dissolved in 15 ml of dioxan. 5 ml of water and 2N aqueous NaOH was added to the solution to give a pH of 13. The reaction solution was heated at 60° C. for 4 h and stirred at room temperature for 16 h. The reaction solution was cooled to 0° C. and concentrated hydrochloric acid was added to give a pH of 1-2, whereupon the product precipitated from solution. The suspension was stirred for 30 min, then the product was filtered off and dried under reduced pressure.
Reaction SMILES: [Si:1]([O:8][CH:9]([C@@H:11]1[C@:28]2([CH3:29])[C@H:14]([C@H:15]3[C@H:25]([CH2:26][CH2:27]2)[C@:23]2([CH3:24])[C:18]([CH2:19][CH:20]([OH:30])[CH2:21][CH2:22]2)=[CH:17][C:16]3([CH3:32])O)[CH2:13][CH2:12]1)[CH3:10])([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2]>C1(C)C=CC=CC=1.C1(=O)CCCCC1>[Si:1]([O:8][CH:9]([C@@H:11]1[C@:28]2([CH3:29])[C@H:14]([C@H:15]3[C@H:25]([CH2:26][CH2:27]2)[C@:23]2([CH3:24])[C:18](=[CH:19][C:20](=[O:30])[CH2:21][CH2:22]2)[CH:17]=[C:16]3[CH3:32])[CH2:13][CH2:12]1)[CH3:10])([C:4]([CH3:5])([CH3:6])[CH3:7])([CH3:3])[CH3:2]
Reactant: CC(O[Si](C)(C)C(C)(C)C)[C@H]1CC[C@H]2[C@H]3[C@H](CC[C@]12C)[C@@]1(C)CCC(O)CC1=CC3(C)O
Solvent: Cc1ccccc1
Solvent: O=C1CCCCC1
Product: CC1=CC2=CC(=O)CC[C@]2(C)[C@H]2CC[C@]3(C)[C@@H](C(C)O[Si](C)(C)C(C)(C)C)CC[C@H]3[C@H]12
Temperature: 40 °C
Reaction time: 0.17 h

Procedure:
A solution of 20-tert-butyldimethylsilyloxy-7-methyl-pregn-5-ene-3,7-diol (298 gm, 0.59 mol) in toluene (3 L) and cyclohexanone (1.03 L) was azeotroped to remove 750 mL of solvent. A solution of aluminum isopropoxide (121 gm) in toluene (620 mL) was added and the solution azeotroped to remove another 650 mL of solvent. A reflux condenser was added and the solution refluxed overnight. The solution was cooled to 40° C. and Supercell® (125 gm) and water (125 mL) were added. After stirring for 10 min, the mixture was filtered and the solids washed with toluene (550 mL). The solvent was removed by rotoevaporation to yield a orange liquid which was purified by column chromatography on silica gel eluted with hexane, followed by 5-10% ethyl acetate in hexanes. The title compound was isolated as a mixture of 20α- and 20β-isomers (199.4 gm, 76% yield).
Reaction SMILES: O.[NH:2]1[C:10](=[O:11])[C:8](=[O:9])[C:6](=[O:7])[NH:5][C:3]1=[O:4].[Br:12][C:13]1[CH:14]=[C:15]2[C:19](=[CH:20][CH:21]=1)[NH:18][CH:17]=[CH:16]2.Cl>C(O)C>[OH:9][C:8]1([C:16]2[C:15]3[C:19](=[CH:20][CH:21]=[C:13]([Br:12])[CH:14]=3)[NH:18][CH:17]=2)[C:6](=[O:7])[NH:5][C:3](=[O:4])[NH:2][C:10]1=[O:11]
Reactant: Brc1ccc2[nH]ccc2c1
Reactant: O=C1NC(=O)C(=O)C(=O)N1
Agent: Cl
Solvent: CCO
Solvent: O
Product: O=C1NC(=O)C(O)(c2c[nH]c3ccc(Br)cc23)C(=O)N1
Reaction time: 0.25 h
Yield: 93.8 %

Procedure:
Alloxan hydrate (1.6 g., 0.01 mole) was dissolved in 40 ml. of ethanol by heating. 5-Bromoindole (1.96 g., 0.01 mole) was added and heating near reflux continued for 15 minutes. Tlc did not indicate that reaction had occured. 1N Hydrochloric acid (10 ml.) was then added while maintaining the reaction near reflux. After 10 minutes, the reaction was concentrated to wet solids. Trituration of these wet solids with water gave the title product [3.17 g., m.p. >250° C.; Rf 0.45 (1:1 ethyl acetate:hexane/5% acetic acid); Rf 0.3 (1:5 ethyl acetate:hexane/5% acetic acid)].
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]([NH2:11])[C:5]2[N:6]([CH:8]=[CH:9][N:10]=2)[CH:7]=1.[CH:12]([N:15]([CH:18](C)C)CC)(C)C.C(Cl)(Cl)=[O:22].C1(C)C=CC=CC=1.CN>C1COCC1>[Br:1][C:2]1[CH:3]=[C:4]([NH:11][C:12]([NH:15][CH3:18])=[O:22])[C:5]2[N:6]([CH:8]=[CH:9][N:10]=2)[CH:7]=1
Reactant: O=C(Cl)Cl
Reactant: CCN(C(C)C)C(C)C
Reactant: Nc1cc(Br)cn2ccnc12
Agent: CN
Solvent: C1CCOC1
Solvent: Cc1ccccc1
Product: CNC(=O)Nc1cc(Br)cn2ccnc12
Temperature: 0 °C

Procedure:
To 6-Bromo-imidazo[1,2-a]pyridin-8-ylamine (1.045 g, 4.93 mmol) in THF (100 mL) was added diisopropylethylamine (1.7 mL, 2.5 eq), and the resulting mixture was cooled to 0° C. With stirring, a solution of 20% phosgene in toluene (3.11 mL, 1.2 eq) was added and the resulting mixture was stirred at 0° C. for 20 minutes. Next, a 2.0M solution of methylamine in THF (24.6 mL, 10 eq) was added and the resulting mixture was stirred from 0° C. to room temperature overnight. Then next day, the solvent was removed under reduced pressure at 55° C., and ethyl acetate (175 mL) and water (50 mL) were added. The resulting mixture was stirred vigorously for 10 minutes and then the layers were separated. The organic layer was dried over magnesium sulfate, filtered and concentrated to give 1-(6-Bromo-imidazo[1,2-a]pyridin-8-yl)-3-methyl-urea as an off-white foamy powder (1.074 g).
Reaction SMILES: C(=O)([O-])[O-].[K+].[K+].[CH2:7]([CH:9]([CH2:12][CH2:13][CH2:14][CH3:15])[CH2:10][NH2:11])[CH3:8].[CH:16]1[C:25]2[C:20](=[CH:21][CH:22]=[CH:23][CH:24]=2)[CH:19]=[CH:18][C:17]=1[O:26][CH2:27][CH2:28][CH2:29][CH2:30]Cl>CS(C)=O.O>[CH2:7]([CH:9]([CH2:12][CH2:13][CH2:14][CH3:15])[CH2:10][NH:11][CH2:30][CH2:29][CH2:28][CH2:27][O:26][C:17]1[CH:18]=[CH:19][C:20]2[C:25](=[CH:24][CH:23]=[CH:22][CH:21]=2)[CH:16]=1)[CH3:8]
Reactant: CCCCC(CC)CN
Reactant: ClCCCCOc1ccc2ccccc2c1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CS(C)=O
Product: CCCCC(CC)CNCCCCOc1ccc2ccccc2c1
Temperature: 140 °C

Procedure:
A mixture of anhydrous potassium carbonate (10 gm, in excess) and 2-ethyl-n-hexylamine (0.33 ml, 0.003 mole) was taken in dry DMSO (40 ml). Now 4-(2-naphthyloxy)-1-chlorobutane (0.5 gm, 0.002 mole) was added in it. Reaction mixture was refluxed at 140° C. for 7 hrs and the reaction was completed as checked by TLC. Reaction mixture was poured in distilled water (60 ml) and extracted with ethyl acetate thrice. The organic layer was separated and concentrated to get oily compound which was later crystallized by benzene hexane to get N-(2-ethyl-n-hexyl)-(4-(naphthalen-2-yloxy)butyl)amine, solid, m.p. 94° C., (yield 0.61 gm, 87.3%).
Reaction SMILES: [N+:1]([CH:4]=[CH:5][C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1)([O-])=O.Cl.[NH2:13][CH2:14][CH2:15][C:16]([O:18][CH2:19][CH3:20])=[O:17].C(N(CC)C(C)C)(C)C>C(#N)C.[Zn]>[NH2:1][CH2:4][CH:5]([NH:13][CH2:14][CH2:15][C:16]([O:18][CH2:19][CH3:20])=[O:17])[C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1
Reactant: O=[N+]([O-])C=Cc1ccccc1
Reactant: CCOC(=O)CCN
Agent: Cl
Agent: [Zn]
Solvent: CC#N
Solvent: CCN(C(C)C)C(C)C
Product: CCOC(=O)CCNC(CN)c1ccccc1
Temperature: 0 °C
Reaction time: 0.25 h
Yield: 148.3 %

Procedure:
Trans-□-Nitrostyrene (4.04 g, 27.1 mmol) was added to a solution of ethyl 3-aminopropanoate hydrochloride (4.16 g, 27.1 mmol), and N,N-diisopropylethylamine (9.43 mL, 54.2 mmol) in acetonitrile (70 mL). After 15 min, anhydrous hydrochloric acid gas was bubbled into the solution until acidic. The mixture was concentrated, redissolved in ethanol (60 mL) and aqueous hydrochloric acid (12 M; 30 mL), and cooled to 0° C. Zinc dust (8.80 g, 134 mmol) was added in portions over 5 min. After 0.5 h, the mixture was concentrated to remove ethanol and saturated aqueous sodium carbonate was added. The mixture was extracted with dichloromethane (3×), and the combined organic extracts were dried over magnesium sulfate, filtered and concentrated to give the title compound (9.5 g). MS 237 (M+1).
Reaction SMILES: [CH3:1][C:2]([N+:15]([O-])=O)([CH3:14])[CH:3](Cl)[C:4]1[CH:9]=[CH:8][C:7]2[O:10][CH2:11][O:12][C:6]=2[CH:5]=1.C([O-])(=O)C.[Na+].C.[H][H]>C(O)(=O)C.[Pt]=O>[CH3:14][C:2]([NH2:15])([CH3:1])[CH2:3][C:4]1[CH:9]=[CH:8][C:7]2[O:10][CH2:11][O:12][C:6]=2[CH:5]=1
Reactant: [H][H]
Reactant: CC(C)(C(Cl)c1ccc2c(c1)OCO2)[N+](=O)[O-]
Agent: O=[Pt]
Agent: CC(=O)[O-]
Agent: [Na+]
Solvent: CC(=O)O
Product: CC(C)(N)Cc1ccc2c(c1)OCO2
Reaction time: 5 h

Procedure:
A mixture of 51.52 g (0.2 mole) of 1,1-dimethyl-2-chloro-2-(3,4-methylenedioxyphenyl)nitroethane, 2.0 g of 83.8 weight % purity platinum oxide, 18.0 g (0.22 mole) of sodium acetate and 4.0 g of "Darco" in 96 ml of acetic acid and 500 ml of SDA-30 was stirred under a hydrogen atmosphere at 1000 p.s.i. and 100° C for a period of 5 hours, after which uptake of hydrogen ceased. The solution was cooled and filtered, and the filtrate was concentrated to an oil which was treated with 400 ml of water. The mixture was extracted twice with ether, after which the aqueous layer was made alkaline by addition of 20% aqueous sodium hydroxide and extracted four times with chloroform. The combined extracts were filtered through "Dicalite" (Trade Mark), washed with water, dried and concentrated to a light yellow oil which was distilled using a 2" 19.38 distillation column to give 1,1-dimethyl-2-(3,4-methylenedioxyphenyl)ethylamine as a clear colourless oil, b.p. 68°-85° C, 0.06-0.04 mm Hg (Yield 24.4 g, 63.2%)
Reaction SMILES: [CH3:1][S:2]([C:5]1[CH:6]=[C:7]([CH2:11][OH:12])[CH:8]=[CH:9][CH:10]=1)(=[O:4])=[O:3].C1C=C[NH+]=CC=1.[O-][Cr](Cl)(=O)=O>C(Cl)Cl>[CH3:1][S:2]([C:5]1[CH:6]=[C:7]([CH:8]=[CH:9][CH:10]=1)[CH:11]=[O:12])(=[O:3])=[O:4]
Reactant: CS(=O)(=O)c1cccc(CO)c1
Agent: O=[Cr](=O)([O-])Cl
Agent: c1cc[nH+]cc1
Solvent: ClCCl
Product: CS(=O)(=O)c1cccc(C=O)c1
Yield: 74.2 %

Procedure:
A solution of [3-(methylsulfonyl)phenyl]methanol (680 mg, 3.66 mmol) in anhydrous CH2Cl2 (20 mL) was treated with PCC (1.03 g, 4.75 mmol) at room temperature for 2 hours. The solvent was removed and the residue was purified by flash column chromatography (20–60% EtOAc in hexanes) to give the product (500 mg, 74% yield). 1H NMR (300 MHz, CDCl3) δ: 3.13 (s, 3 H), 7.77–7.82 (m, 1 H), 8.18–8.24 (m, 2 H), 8.46–8.48 (m, 1 H), 10.12 (s, 1 H).
Reaction SMILES: [CH2:1]([O:3][C:4](=[O:39])[CH2:5][CH:6]([C:29]1[CH:38]=[N:37][C:36]2[C:31](=[CH:32][CH:33]=[CH:34][CH:35]=2)[N:30]=1)[CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][C:13]1[CH:18]=[CH:17][CH:16]=[C:15]([NH:19][CH2:20][C:21]2[CH:26]=[CH:25][C:24]([O:27][CH3:28])=[CH:23][CH:22]=2)[N:14]=1)[CH3:2].C=O.[C:42](O)(=O)C.[BH3-]C#N.[Na+]>CO>[CH2:1]([O:3][C:4](=[O:39])[CH2:5][CH:6]([C:29]1[CH:38]=[N:37][C:36]2[C:31](=[CH:32][CH:33]=[CH:34][CH:35]=2)[N:30]=1)[CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][C:13]1[CH:18]=[CH:17][CH:16]=[C:15]([N:19]([CH2:20][C:21]2[CH:22]=[CH:23][C:24]([O:27][CH3:28])=[CH:25][CH:26]=2)[CH3:42])[N:14]=1)[CH3:2]
Reactant: CCOC(=O)CC(CCCCCCc1cccc(NCc2ccc(OC)cc2)n1)c1cnc2ccccc2n1
Reactant: CC(=O)O
Agent: C=O
Agent: [BH3-]C#N
Agent: [Na+]
Solvent: CO
Product: CCOC(=O)CC(CCCCCCc1cccc(N(C)Cc2ccc(OC)cc2)n1)c1cnc2ccccc2n1
Temperature: 50 °C
Reaction time: 0.25 h
Yield: 99.2 %

Procedure:
To a solution of 22-5 (0.130 g, 0.246 mmol) in methanol (5 mL) was added paraformaldehyde (0.07 g) and acetic acid (0.071 mL, 1.23 mmol). After stirring at 50° C. for 15 minutes, NaCNBH3 (0.020 g, 0.32 mmol) was added. After stirring 2 hours the solution was concentrated in vacuo. The residue was dissolved in CHCl3 (125 mL) and washed with saturated NaHCO3, dried, and concentrated to afford 22-6 (0.132 g).