Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH2:1]([O:3][C:4](=[O:21])[CH2:5][C@@H:6]([N:10]1[C:14]2=[N:15][C:16]([CH3:19])=[CH:17][CH:18]=[C:13]2[NH:12][C:11]1=[O:20])[CH2:7][CH2:8][CH3:9])[CH3:2].C([O-])([O-])=O.[K+].[K+].[I-].[CH3:29][N:30]1[C:38]2[C:33](=[C:34]([CH3:39])[CH:35]=[CH:36][CH:37]=2)[C:32]([CH2:40][N+](C)(C)C)=[CH:31]1>CN(C=O)C.C(OCC)(=O)C>[CH2:1]([O:3][C:4](=[O:21])[CH2:5][C@@H:6]([N:10]1[C:14]2=[N:15][C:16]([CH3:19])=[CH:17][CH:18]=[C:13]2[N:12]([CH2:40][C:32]2[C:33]3[C:38](=[CH:37][CH:36]=[CH:35][C:34]=3[CH3:39])[N:30]([CH3:29])[CH:31]=2)[C:11]1=[O:20])[CH2:7][CH2:8][CH3:9])[CH3:2]
Reactant: CCC[C@@H](CC(=O)OCC)n1c(=O)[nH]c2ccc(C)nc21
Reactant: Cc1cccc2c1c(C[N+](C)(C)C)cn2C
Agent: O=C([O-])[O-]
Agent: [I-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: CCOC(C)=O
Product: CCC[C@@H](CC(=O)OCC)n1c(=O)n(Cc2cn(C)c3cccc(C)c23)c2ccc(C)nc21
Temperature: 60 °C
Yield: 44.6 %

Procedure:
To a solution of (S)-3-(5-methyl-2-oxo-1,2-dihydro-imidazo[4,5-b]pyridin-3-yl)-hexanoic acid ethyl ester (247 mg, 0.85 mmol) in DMF (5 mL) were added K2CO3 (234 mg, 1.7 mmol) and (1,4-dimethyl-1H-indol-3-ylmethyl)-trimethyl-ammonium iodide (438 mg, 1.27 mmol). The reaction mixture was heated to 60° C. for 48 hours. The reaction mixture was diluted with ethyl acetate and washed with water (×4). The organic phase was dried over Na2SO4 and concentrated. The resulting residue was purified by silica gel preparative TLC using 98:2 CH2Cl2:MeOH as an eluent to afford 170 mg (45%) of the title compound. LCMS, M++1, m/z: 449.47.
Reaction SMILES: [CH2:1]([O:8][C:9]1[CH:10]=[CH:11][C:12]([C:15]2[C:19]3=[N:20][CH:21]=[CH:22][CH:23]=[C:18]3[NH:17][N:16]=2)=[N:13][CH:14]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C([O-])([O-])=O.[K+].[K+].I[CH:31]([CH3:33])[CH3:32].C([O-])(O)=O.[Na+]>CN(C=O)C>[CH2:1]([O:8][C:9]1[CH:10]=[CH:11][C:12]([C:15]2[C:19]3=[N:20][CH:21]=[CH:22][CH:23]=[C:18]3[N:17]([CH:31]([CH3:33])[CH3:32])[N:16]=2)=[N:13][CH:14]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: c1ccc(COc2ccc(-c3n[nH]c4cccnc34)nc2)cc1
Reactant: CC(C)I
Agent: O=C([O-])O
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: CC(C)n1nc(-c2ccc(OCc3ccccc3)cn2)c2ncccc21
Temperature: 25 °C
Reaction time: 72 h

Procedure:
A mixture of 3-[5-(benzyloxy)pyridin-2-yl]-1H-pyrazolo[4,3-b]pyridine (237 mg), K2CO3 (217 mg) in DMF (3 mL) was added 2-iodopropane (0.102 mL), and stirred at room temperature for 72 h. The mixture was poured into saturated NaHCO3 aqueous solution and extracted with AcOEt. The organic layer was separated, washed with brine, dried over MgSO4 and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (AcOEt/hexane) to give the title compound (219 mg).
Reaction SMILES: [CH2:1]1[C:9]2[CH:8]=[CH:7][CH:6]=[C:5]([OH:10])[C:4]=2[CH2:3][CH2:2]1.[N+:11]([O-])([OH:13])=[O:12]>C(O)(=O)C>[OH:10][C:5]1[C:4]2[CH:3]=[CH:2][CH2:1][C:9]=2[CH:8]=[CH:7][C:6]=1[N+:11]([O-:13])=[O:12]
Reactant: O=[N+]([O-])O
Reactant: Oc1cccc2c1CCC2
Solvent: CC(=O)O
Product: O=[N+]([O-])c1ccc2c(c1O)C=CC2
Reaction time: 0.5 h

Procedure:
The starting material, 4-indanol (i.e., Formula 5) is dissolved in an organic acid, preferably glacial acetic acid, at a temperature in the range of about 20°-30° C., preferably about room temperature. To this solution is added in a gradual manner a solution of concentrated nitric acid (about 1 to 2 molar equivalents, preferably about 1.5 molar equivalents) in an organic acid, preferably glacial acetic acid. The reaction mixture is stirred for a period of about 15 minutes to 1 hour, preferably about 30 minutes, at a temperature in the range of 20°-30° C., preferably about room temperature. When the reaction is substantially complete, the 4-hydroxy-5-nitrobenzocyclopentene of Formula 6 is isolated and purified by conventional means, preferably by flash column chromatography.
Reaction SMILES: [F:1][CH2:2][C:3]([C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][C:6]=1[F:11])=O.[C:12]([S@:16]([NH2:18])=[O:17])([CH3:15])([CH3:14])[CH3:13]>>[F:1][CH2:2]/[C:3](=[N:18]/[S@@:16]([C:12]([CH3:15])([CH3:14])[CH3:13])=[O:17])/[C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][C:6]=1[F:11]
Reactant: O=C(CF)c1ccccc1F
Reactant: CC(C)(C)[S@](N)=O
Product: CC(C)(C)[S@@](=O)/N=C(/CF)c1ccccc1F
Yield: 62 %

Procedure:
In a manner analogous to that described for the preparation of sulfinyl imine E2.1 the reaction of 2-fluoro-1-(2-fluoro-phenyl)-ethanone with (R)-tert-butylsulfinamide yielded the (R)-2-methyl-propane-2-sulfinic acid [2-fluoro-1-(2-fluoro-phenyl)-eth-(E)-ylidene]-amide (62% yield) as an orange oil. MS (ISP): m/z=260.2 [M+H]+.
Reaction SMILES: [C:1]([N:9]1[CH2:13][CH2:12][C@@H:11]([NH:14][CH3:15])[CH2:10]1)(=O)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:16]1([CH:22]([N:29]=[C:30]=[O:31])[C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1>C(Cl)Cl>[CH:22]([NH:29][C:30](=[O:31])[N:14]([C@@H:11]1[CH2:12][CH2:13][N:9]([CH2:1][C:2]2[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=2)[CH2:10]1)[CH3:15])([C:23]1[CH:24]=[CH:25][CH:26]=[CH:27][CH:28]=1)[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1
Reactant: CN[C@@H]1CCN(C(=O)c2ccccc2)C1
Reactant: O=C=NC(c1ccccc1)c1ccccc1
Solvent: ClCCl
Product: CN(C(=O)NC(c1ccccc1)c1ccccc1)[C@@H]1CCN(Cc2ccccc2)C1
Temperature: 25 °C
Reaction time: 8 h
Yield: 96.8 %

Procedure:
To a solution of (R)-(1-benzoyl-pyrrolidin-3-yl)-methyl-amine(0.32 g, 1.68 mmol) in dry CH2Cl2 (5 ml) was added diphenylmethyl isocyanate(0.32 ml, 1.68 mmol) dropwise under nitrogen. The resulting mixture was stirred at room temperature overnight. Removal of solvent under reduced pressure followed by column chromatography using CH2Cl2:CH3OH(15:1) gives 0.65 g of the desired product.
Reaction SMILES: [CH3:1][C:2]1[C:10]2[N:9]=[CH:8][NH:7][C:6]=2[CH:5]=[CH:4][C:3]=1[C:11]#[N:12].C1COCC1.[O:18]1[CH:23]=[CH:22][CH2:21][CH2:20][CH2:19]1.CC1C=CC(S(O)(=O)=O)=CC=1.O>CCOC(C)=O>[CH3:1][C:2]1[C:10]2[N:9]=[CH:8][N:7]([CH:19]3[CH2:20][CH2:21][CH2:22][CH2:23][O:18]3)[C:6]=2[CH:5]=[CH:4][C:3]=1[C:11]#[N:12]
Reactant: C1=COCCC1
Reactant: Cc1c(C#N)ccc2[nH]cnc12
Agent: Cc1ccc(S(=O)(=O)O)cc1
Solvent: C1CCOC1
Solvent: O
Solvent: CCOC(C)=O
Product: Cc1c(C#N)ccc2c1ncn2C1CCCCO1
Temperature: 25 °C
Yield: 77.4 %

Procedure:
To a stirred solution of 160 (8.3 g, 52.5 mmol) and THF (100 mL) at RT under nitrogen was added, 3,4-dihydro-2H-pyran (35 g, 420 mmol) and p-TsOH.H2O (0.9 g, 5.3 mmol) and the reaction mixture was heated at 75° C. for 4 h. The mixture was cooled to RT, diluted with EtOAc and sequentially washed with sat'd. aq. NaHCO3, and brine. The organic extract was dried (Na2SO4), filtered and concentrated in vacuo. The crude product was purified by SiO2 chromatography eluting with a MeOH/DCM gradient (0 to 5% MeOH) to afford 9.8 g (77%) of 4-methyl-1-(tetrahydro-2H-pyran-2-yl)-1H-benzo[d]imidazole-5-carbonitrile (162) as a light yellow solid: MS (ESI) m/z=242 [M+1]+.
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[C:4]([C:8]2[N:17]=[C:16]([NH:18][C:19]3[CH:20]=[C:21]4[C:25](=[CH:26][CH:27]=3)[N:24]([C:28]([O:30][C:31]([CH3:34])([CH3:33])[CH3:32])=[O:29])[N:23]=[CH:22]4)[C:15]3[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=3)[N:9]=2)[CH:5]=[CH:6][CH:7]=1.[N:35]1([C:41](Cl)=[O:42])[CH2:40][CH2:39][O:38][CH2:37][CH2:36]1.CCN(CC)CC.[Cl-]>C(Cl)Cl.CN(C1C=CN=CC=1)C>[N:35]1([C:41]([NH:1][C:2]2[CH:3]=[C:4]([C:8]3[N:17]=[C:16]([NH:18][C:19]4[CH:20]=[C:21]5[C:25](=[CH:26][CH:27]=4)[N:24]([C:28]([O:30][C:31]([CH3:34])([CH3:33])[CH3:32])=[O:29])[N:23]=[CH:22]5)[C:15]4[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=4)[N:9]=3)[CH:5]=[CH:6][CH:7]=2)=[O:42])[CH2:40][CH2:39][O:38][CH2:37][CH2:36]1
Reactant: CC(C)(C)OC(=O)n1ncc2cc(Nc3nc(-c4cccc(N)c4)nc4ccccc34)ccc21
Reactant: O=C(Cl)N1CCOCC1
Agent: CN(C)c1ccncc1
Agent: [Cl-]
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: CC(C)(C)OC(=O)n1ncc2cc(Nc3nc(-c4cccc(NC(=O)N5CCOCC5)c4)nc4ccccc34)ccc21
Temperature: 25 °C
Reaction time: 16 h

Procedure:
To a suspension of tert-butyl 5-(2-(3-aminophenyl)quinazolin-4-ylamino)-1H-indazole-1-carboxylate (100 mg, 0.22 mmol) and morpholine-4-carbonyl chloride (51 μL, 0.44 mmol,) in CH2Cl2 (2 mL) was added Et3N (61 μL, 0.44 mmol) and catalytic amount of DMAP. The reaction mixture was stirred at RT for 2 h after which 2 equivalents each of morpholine-4-carbonyl chloride and Et3N were added. After 2 h of stirring another 2 equivalents of both the chloride and Et3N were added and continued to stir at ambient temperature for 16 hours. The reaction was concentrated in vacuo and the residue was purified by flash chromatography on silica (12:1 CH2Cl2:MeOH). The product tert-butyl 5-(2-(3-(morpholine-4-carboxamido)phenyl)quinazolin-4-ylamino)-1H-indazole-1-carboxylate was isolated. (80 mg, 65%)
Reaction SMILES: O.[OH-].[Li+].C[O:5][C:6](=[O:16])[CH:7]([C:9]1[CH:14]=[CH:13][C:12]([I:15])=[CH:11][CH:10]=1)[CH3:8]>O.C1COCC1.CO>[I:15][C:12]1[CH:11]=[CH:10][C:9]([CH:7]([CH3:8])[C:6]([OH:16])=[O:5])=[CH:14][CH:13]=1
Reactant: COC(=O)C(C)c1ccc(I)cc1
Agent: [Li+]
Agent: [OH-]
Solvent: O
Solvent: CO
Solvent: C1CCOC1
Product: CC(C(=O)O)c1ccc(I)cc1
Temperature: 25 °C
Reaction time: 2 h

Procedure:
0.610 g (14.6 mmol) Lithiumhydroxide monohydrate in 15 mL water are added to 2.12 g (7.31 mmol) 2-(4-iodo-phenyl)-propionic acid methyl ester (Bioorg. Med. Chem. Lett. 2010, 20, 896) in 20 mL THF and 12 mL MeOH at 0° C. Cooling is removed and the mixture is stirred at rt for 2 h. After that time, the mixture is acidified with 1 N HCl to pH˜1 and extracted with DCM. The organic layer is washed with brine, dried over sodium sulphate and the solvent is evaporated. The product is used without further purification in Example IV.1.
Reaction SMILES: [O:1]1[CH2:3][CH:2]1[CH:4]([NH:12][C:13](=[O:19])[O:14][C:15]([CH3:18])([CH3:17])[CH3:16])[CH2:5][C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1.[CH3:20][O:21][C:22]1[CH:23]=[C:24]([CH:27]=[CH:28][CH:29]=1)[CH2:25][NH2:26]>C(O)(C)C>[CH2:5]([C@H:4]([NH:12][C:13](=[O:19])[O:14][C:15]([CH3:18])([CH3:17])[CH3:16])[C@H:2]([OH:1])[CH2:3][NH:26][CH2:25][C:24]1[CH:27]=[CH:28][CH:29]=[C:22]([O:21][CH3:20])[CH:23]=1)[C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1
Reactant: COc1cccc(CN)c1
Reactant: CC(C)(C)OC(=O)NC(Cc1ccccc1)C1CO1
Solvent: CC(C)O
Product: COc1cccc(CNC[C@@H](O)[C@H](Cc2ccccc2)NC(=O)OC(C)(C)C)c1

Procedure:
tert-Butyl 1-(2-oxiranyl)-2-phenylethylcarbamate (V, commercially available, 20 g, 76 mmole) is dissolved in i-propanol (380 ml). To this mixture is added 3-methoxybenzyl amine (49 ml, 380 mmole). The reaction mixture is heated to reflux for 1 hr (when HPLC indicated complete reaction). The reaction mixture is concentrated under reduced pressure and the residue is treated with hexane (500 ml). The product is isolated by filtration. The mother liquors are concentrated under reduced pressure to give additional crude material which is partitioned between ethyl acetate (50 ml) and water (50 ml). The mixture is acidified with concentrated hydrochloric acid (to pH=4), the organic phase is separated and washed with water, saline, dried over sodium sulfate and then concentrated under reduced pressure to give additional title compound, M+H=401.
Reaction SMILES: [O:1]1CCCC1.[Si:6]([O:13][C@@H:14]([C@@H:16]1[C@@H:19]([C@@H:20]([CH3:40])[C:21](C2C=C(C)C=CC=2S(NC2CCCCC2)(=O)=O)=[O:22])[NH:18][C:17]1=[O:41])[CH3:15])([C:9]([CH3:12])([CH3:11])[CH3:10])([CH3:8])[CH3:7].[OH-].[Na+]>O>[Si:6]([O:13][C@@H:14]([C@@H:16]1[C@@H:19]([C@@H:20]([CH3:40])[C:21]([OH:22])=[O:1])[NH:18][C:17]1=[O:41])[CH3:15])([C:9]([CH3:10])([CH3:11])[CH3:12])([CH3:7])[CH3:8]
Reactant: Cc1ccc(S(=O)(=O)NC2CCCCC2)c(C(=O)[C@H](C)[C@H]2NC(=O)[C@@H]2[C@@H](C)O[Si](C)(C)C(C)(C)C)c1
Reactant: C1CCOC1
Agent: [Na+]
Agent: [OH-]
Solvent: O
Product: C[C@@H](O[Si](C)(C)C(C)(C)C)[C@H]1C(=O)N[C@@H]1[C@@H](C)C(=O)O
Reaction time: 3 h
Yield: 69 %

Procedure:
To a tetrahydrofuran solution (2:1, 3.5 ml) of 3-{(2R)-2-[(3S,4R)-3-[(1R)-1-tert-butyldimethylsilyloxyethyl]-2-oxoazetidin-4-yl]propionyl}-N-cyclohexyl-p-toluenesulfonamide (218 mg, 0.4 mmol, β:α=88:12), 0.5N aqueous sodium hydroxide (1.8 ml) was added dropwise at room temperature, followed by stirring for 3 hours at the same temperature. To the reaction mixture, 5 ml of water was then poured and the resulting mixture was washed with methylene chloride. The aqueous layer was acidified to pH 2 with 2N-hydrochloric acid. The crystals so precipitated were collected by filtration, washed with water, and then dried under reduced pressure, whereby 84 mg (β:α=89:11) of the colorless title compound was obtained (yield: 69%).
Reaction SMILES: [C:1]([C:5]1[CH:10]=[CH:9][C:8]([C:11](=[O:28])[C:12]([C:14]2[CH:23]=[CH:22][C:21]3[C:20]([CH3:25])([CH3:24])[CH2:19][CH2:18][C:17]([CH3:27])([CH3:26])[C:16]=3[CH:15]=2)=[O:13])=[CH:7][CH:6]=1)([O:3]C)=[O:2].C(O)(=O)C.O>S(=O)(=O)(O)O>[C:1]([C:5]1[CH:10]=[CH:9][C:8]([C:11](=[O:28])[C:12]([C:14]2[CH:23]=[CH:22][C:21]3[C:20]([CH3:24])([CH3:25])[CH2:19][CH2:18][C:17]([CH3:27])([CH3:26])[C:16]=3[CH:15]=2)=[O:13])=[CH:7][CH:6]=1)([OH:3])=[O:2]
Reactant: COC(=O)c1ccc(C(=O)C(=O)c2ccc3c(c2)C(C)(C)CCC3(C)C)cc1
Agent: O=S(=O)(O)O
Solvent: O
Solvent: CC(=O)O
Product: CC1(C)CCC(C)(C)c2cc(C(=O)C(=O)c3ccc(C(=O)O)cc3)ccc21
Yield: 85.1 %

Procedure:
3.9 g (10 mmol) of 1-(4-Carbomethoxyphenyl)-2-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)ethanedione (Example 6) were refluxed in a mixture of 5 ml of concentrated sulfuric acid, 80 ml of glacial acetic acid and 40 ml of water for 8 h. The mixture was then poured into 500 ml of water, and the crystalline precipitate was filtered off with suction and washed with water until the washings were neutral. The dried crude product was recrystallized from cyclohexane, yielding 3.1 g of the title compound of melting point 148°-151° C.
Reaction SMILES: [NH2:1][C:2]1[CH:20]=[CH:19][C:5]([O:6][C:7]2[C:16]3[NH:15][C:14](=[O:17])[C:13](=[O:18])[NH:12][C:11]=3[N:10]=[CH:9][CH:8]=2)=[CH:4][CH:3]=1.[Cl:21][C:22]1[CH:27]=[CH:26][C:25]([N:28]=[C:29]=[O:30])=[CH:24][C:23]=1[C:31]([F:34])([F:33])[F:32]>>[Cl:21][C:22]1[CH:27]=[CH:26][C:25]([NH:28][C:29]([NH:1][C:2]2[CH:20]=[CH:19][C:5]([O:6][C:7]3[C:16]4[NH:15][C:14](=[O:17])[C:13](=[O:18])[NH:12][C:11]=4[N:10]=[CH:9][CH:8]=3)=[CH:4][CH:3]=2)=[O:30])=[CH:24][C:23]=1[C:31]([F:32])([F:33])[F:34]
Reactant: O=C=Nc1ccc(Cl)c(C(F)(F)F)c1
Reactant: Nc1ccc(Oc2ccnc3[nH]c(=O)c(=O)[nH]c23)cc1
Product: O=C(Nc1ccc(Oc2ccnc3[nH]c(=O)c(=O)[nH]c23)cc1)Nc1ccc(Cl)c(C(F)(F)F)c1
Yield: 38 %

Procedure:
Method F2 was used with 8-(4-aminophenoxy)pyrido[2,3-b]pyrazine-2,3(1H,4H)-dione and 4-chloro-3-trifluoromethylphenyl isocyanate to obtain the title compound (yield 38%).
Reaction SMILES: [OH-].[Na+].C1(C)C=CC(S(NN=[C:14]([C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)[C:15]([N:17]2[CH2:22][CH2:21][CH2:20][CH2:19][CH2:18]2)=[O:16])(=O)=O)=CC=1>[Cl-].C([N+](CCCCCCCC)(CCCCCCCC)C)CCCCCCC.C1(C)C=CC=CC=1>[C:23]1([CH:14]2[C:15](=[O:16])[N:17]3[CH:18]2[CH2:19][CH2:20][CH2:21][CH2:22]3)[CH:24]=[CH:25][CH:26]=[CH:27][CH:28]=1
Reactant: Cc1ccc(S(=O)(=O)NN=C(C(=O)N2CCCCC2)c2ccccc2)cc1
Agent: CCCCCCCC[N+](C)(CCCCCCCC)CCCCCCCC
Agent: [Cl-]
Agent: [Na+]
Solvent: Cc1ccccc1
Product: O=C1C(c2ccccc2)C2CCCCN12
Temperature: 0 °C
Yield: 102.8 %

Procedure:
Sodium hydroxide, 50% aqueous solution (1.09 Kg, 13.6 mol, 1.05 eq) was added to a stirred mixture of 1-(phenylglyoxylyl)piperidine p-toluenesulfonylhydrazone (5.00 Kg, 13.0 mol, 1 eq), phase transfer catalyst (PTC) trioctylmethylammonium chloride (aliquat 336) (60.0 g, 0.15 mol, 0.01 eq) and toluene (50 L) at 20–30° C. The mixture was heated to reflux and monitored by both TLC and the color of the reaction mixture. The originally yellow solution in 10 minutes turned bright orange as the diazo compound was formed. After 6.5 hours at reflux, the solution re-assumed a yellow color and TLC indicated that no starting material was present. Crushed ice (20 Kg) was added to the reaction mixture (temperature of the mixture was dropped to 15° C.). The organic layer was separated, washed with brine (15 L) and evaporated under reduced pressure to give 2.69 Kg (quantitative yield) of 7-phenyl-1-azabicyclo [4.2.0]octan-8-one with R*R*/S*R* 3.3:1 by GC.
Reaction SMILES: [H-].[H-].[H-].[H-].[Li+].[Al+3].[CH2:7]([N:14]1[CH2:19][CH2:18][N:17]([CH2:20][C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)[CH2:16][CH:15]1[C:27]([NH2:29])=O)[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1>C1COCC1>[CH2:7]([N:14]1[CH2:19][CH2:18][N:17]([CH2:20][C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)[CH2:16][CH:15]1[CH2:27][NH2:29])[C:8]1[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=1
Reactant: NC(=O)C1CN(Cc2ccccc2)CCN1Cc1ccccc1
Agent: [Al+3]
Agent: [H-]
Agent: [Li+]
Solvent: C1CCOC1
Product: NCC1CN(Cc2ccccc2)CCN1Cc1ccccc1
Temperature: 25 °C
Yield: 99 %

Procedure:
To a stirred suspension of LAH (0.9 g, 25.9 mmol) in dry THF (150 mL) was added 1,4-dibenzyl-piperazine-2-carboxylic acid amide (4.0 g, 12.93 mmol) and the mixture was stirred under reflux for 20 h (monitored by TLC). The stirred mixture was cooled with an ice-bath and quenched with Rochelle's salt (6 mL), warmed to room temperature, and the suspension was poured over a pad of silica gel (20 mm). The celite was washed with 15% MeOH in CH2Cl2 with 1% NH4OH (3×50 mL) and eluted through pad of silica gel. Th eluent was concentrated under reduced pressure to give the desired product in 99% yield.
Reaction SMILES: [CH:1]([N:4]1[C:8]2[CH:9]=[CH:10][CH:11]=[CH:12][C:7]=2[NH:6][S:5]1(=[O:14])=[O:13])([CH3:3])[CH3:2].[Cl:15][CH2:16][CH2:17][C@@H:18]([C:20]1[CH:25]=[C:24]([F:26])[CH:23]=[C:22]([Cl:27])[CH:21]=1)O.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OC(C)C)=O)=NC(OC(C)C)=O>O1CCCC1>[Cl:15][CH2:16][CH2:17][C@@H:18]([N:6]1[C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][C:8]=2[N:4]([CH:1]([CH3:3])[CH3:2])[S:5]1(=[O:13])=[O:14])[C:20]1[CH:25]=[C:24]([F:26])[CH:23]=[C:22]([Cl:27])[CH:21]=1
Reactant: O[C@@H](CCCl)c1cc(F)cc(Cl)c1
Reactant: CC(C)N1c2ccccc2NS1(=O)=O
Agent: CC(C)OC(=O)N=NC(=O)OC(C)C
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: C1CCOC1
Product: CC(C)N1c2ccccc2N([C@H](CCCl)c2cc(F)cc(Cl)c2)S1(=O)=O
Temperature: 25 °C
Reaction time: 8 h
Yield: 82.3 %

Procedure:
To mixture of 1-isopropyl-1,3-dihydro-2,1,3-benzothiadiazole 2,2-dioxide (1.28 g, 6.00 mmol), (1S)-3-chloro-1-(3-chloro-5-fluorophenyl)propan-1-ol (1.34 g, 6.00 mmol) and triphenylphosphine (1.73 g, 6.60 mmol, 1.1 equiv.) in tetrahydrofuran (20 mL) under nitrogen was added slowly diisopropyl azodicarboxylate (1.28 mL, 6.60 mmol, 1.1 equiv.) via a syringe at 0° C. The resulting solution was stirred at room temperature overnight. Solvent was removed under reduced pressure and the viscous brown liquid residue was purified using Isco CombiFlash Companion column chromatography (silica gel, 0-15% ethyl acetate/hexane) to give 2.06 g (82%) of 1-[(1R)-3-chloro-1-(3-chloro-5-fluorophenyl)propyl]-3-isopropyl-1,3-dihydro-2,1,3-benzothiadiazole 2,2-dioxide as a white solid.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:10]=[CH:9][C:6]([CH:7]=[O:8])=[C:5]([O:11][CH2:12][CH:13]2[CH2:18][CH:17]([O:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][CH2:34][CH2:35][CH2:36][CH3:37])[CH:16]([O:38][CH2:39][CH2:40][CH2:41][CH2:42][CH2:43][CH2:44][CH2:45][CH2:46][CH2:47][CH2:48][CH2:49][CH2:50][CH2:51][CH2:52][CH2:53][CH2:54][CH2:55][CH3:56])[CH:15]([O:57][CH2:58][CH2:59][CH2:60][CH2:61][CH2:62][CH2:63][CH2:64][CH2:65][CH2:66][CH2:67][CH2:68][CH2:69][CH2:70][CH2:71][CH2:72][CH2:73][CH2:74][CH3:75])[CH2:14]2)[CH:4]=1.[BH4-].[Na+].Cl>C1COCC1.CO>[CH3:1][O:2][C:3]1[CH:10]=[CH:9][C:6]([CH2:7][OH:8])=[C:5]([O:11][CH2:12][CH:13]2[CH2:18][CH:17]([O:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][CH2:34][CH2:35][CH2:36][CH3:37])[CH:16]([O:38][CH2:39][CH2:40][CH2:41][CH2:42][CH2:43][CH2:44][CH2:45][CH2:46][CH2:47][CH2:48][CH2:49][CH2:50][CH2:51][CH2:52][CH2:53][CH2:54][CH2:55][CH3:56])[CH:15]([O:57][CH2:58][CH2:59][CH2:60][CH2:61][CH2:62][CH2:63][CH2:64][CH2:65][CH2:66][CH2:67][CH2:68][CH2:69][CH2:70][CH2:71][CH2:72][CH2:73][CH2:74][CH3:75])[CH2:14]2)[CH:4]=1
Reactant: CCCCCCCCCCCCCCCCCCOC1CC(COc2cc(OC)ccc2C=O)CC(OCCCCCCCCCCCCCCCCCC)C1OCCCCCCCCCCCCCCCCCC
Agent: Cl
Agent: [BH4-]
Agent: [Na+]
Solvent: C1CCOC1
Solvent: CO
Product: CCCCCCCCCCCCCCCCCCOC1CC(COc2cc(OC)ccc2CO)CC(OCCCCCCCCCCCCCCCCCC)C1OCCCCCCCCCCCCCCCCCC
Temperature: 25 °C
Reaction time: 1.5 h
Yield: 97 %

Procedure:
4-Methoxy-2-(3′,4′,5′-tris(octadecyloxy)cyclohexylmethyloxy)benzaldehyde (73.56 g, 69.8 mmol) was dissolved in THF-methanol (1100 ml+55 ml), and sodium borohydride (3.17 g, 83.8 mmol) was added at 0° C. After stirring the mixture at room temperature for 1.5 hr, 0.2N hydrochloric acid (150 ml) was added at 0° C. to quench the reaction. The solvent was evaporated to about half, and the residue was dissolved in chloroform (1400 ml), washed twice with 0.1N hydrochloric acid (700 ml), and twice with pure water (700 ml). The solvent was evaporated, and the residue was precipitated with methanol (800 ml), and washed with acetonitrile (800 ml) to give 4-methoxy-2-(3′,4′,5′-tris(octadecyloxy)cyclohexylmethyloxy)benzyl alcohol (71.5 g, 67.7 mmol, 92% vs methyl 3,4,5-tris(octadecyloxy)cyclohexylcarboxylate).
Reaction SMILES: [CH3:1][C:2]1[C:3]([C:13]([O:15][CH3:16])=[O:14])=[CH:4][N:5]([C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=2)[CH:6]=1.IN1C(=O)CCC1=O.[C:25]1([SH:31])[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1.S([O-])([O-])(=O)=S.[Na+].[Na+]>O1CCCC1>[CH3:1][C:2]1[C:3]([C:13]([O:15][CH3:16])=[O:14])=[CH:4][N:5]([C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=2)[C:6]=1[S:31][C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1
Reactant: COC(=O)c1cn(-c2ccccc2)cc1C
Reactant: Sc1ccccc1
Agent: O=C1CCC(=O)N1I
Agent: O=S([O-])([O-])=S
Agent: [Na+]
Solvent: C1CCOC1
Product: COC(=O)c1cn(-c2ccccc2)c(Sc2ccccc2)c1C
Temperature: 25 °C
Reaction time: 48 h
Yield: 100 %

Procedure:
To a solution of methyl 4-methyl-1-phenyl-1H-pyrrole-3-carboxylate (540 mg) in tetrahydrofuran (10 mL) were added N-iodosuccinimide (677 mg) and thiophenol (0.257 mL), and the mixture was stirred at room temperature for 2 days. Saturated aqueous sodium thiosulfate solution (10 mL) was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The extract was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure to give the title compound as a pale-yellow oil (yield 812 mg, about 100%).
Reaction SMILES: [N+]([C:4]1[C:17]2[C:16](=[O:18])[C:15]3[C:10](=[CH:11][C:12]([N+:19]([O-:21])=[O:20])=[CH:13][CH:14]=3)[C:9](=[O:22])[C:8]=2[CH:7]=[CH:6][CH:5]=1)([O-])=O.[CH3:23][O:24][C:25]1[CH:30]=[CH:29][C:28]([NH2:31])=[CH:27][CH:26]=1>[N+](C1C=CC=CC=1)([O-])=O>[CH3:23][O:24][C:25]1[CH:30]=[CH:29][C:28]([NH:31][C:4]2[C:17]3[C:16](=[O:18])[C:15]4[C:10](=[CH:11][C:12]([N+:19]([O-:21])=[O:20])=[CH:13][CH:14]=4)[C:9](=[O:22])[C:8]=3[CH:7]=[CH:6][CH:5]=2)=[CH:27][CH:26]=1
Reactant: O=C1c2cc([N+](=O)[O-])ccc2C(=O)c2c1cccc2[N+](=O)[O-]
Reactant: COc1ccc(N)cc1
Solvent: O=[N+]([O-])c1ccccc1
Product: COc1ccc(Nc2cccc3c2C(=O)c2ccc([N+](=O)[O-])cc2C3=O)cc1
Yield: 99.6 %

Procedure:
100 g of 1,6-dinitro-anthraquinone and 84 g of p-anisidine are stirred in 300 ml of nitrobenzene at 150° C until no further starting material is detectable in a sample. The mixture is now distilled to dryness in a Venuleth apparatus under a vacuum of 5 mm and the finely ground residue is thoroughly stirred with dilute sulphuric acid, filtered off, washed until neutral and dried. 125 g of 1-p-anisidino-6-nitro-anthraquinone are obtained.