Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: Br.[NH:2]([C:4]1[NH:5][CH2:6][CH2:7][N:8]=1)[NH2:3].[OH:9][C@H:10]1[CH2:27][CH2:26][C@@:25]2([CH3:28])[C@H:12]([CH2:13][CH2:14][C@@H:15]3[C@@H:24]2[CH2:23][CH2:22][C@@:20]2([CH3:21])[C@:16]3([OH:31])[CH2:17][CH2:18][C@@H:19]2[CH:29]=O)[CH2:11]1>O.O1CCOCC1>[NH:8]1[CH2:7][CH2:6][N:5]=[C:4]1[NH:2]/[N:3]=[CH:29]/[C@H:19]1[CH2:18][CH2:17][C@:16]2([OH:31])[C@H:15]3[C@H:24]([CH2:23][CH2:22][C@:20]12[CH3:21])[C@:25]1([CH3:28])[C@@H:12]([CH2:11][C@@H:10]([OH:9])[CH2:27][CH2:26]1)[CH2:13][CH2:14]3
Reactant: NNC1=NCCN1
Reactant: C[C@]12CC[C@H](O)C[C@H]1CC[C@@H]1[C@@H]2CC[C@]2(C)[C@@H](C=O)CC[C@]12O
Agent: Br
Solvent: O
Solvent: C1COCCO1
Product: C[C@]12CC[C@H](O)C[C@H]1CC[C@@H]1[C@@H]2CC[C@]2(C)[C@@H](/C=N/NC3=NCCN3)CC[C@]12O
Reaction time: 2 h
Yield: 43.4 %

Procedure:
To a solution of 0.93 g of 2-hydrazino-2-imidazoline hydrobromide in 45 ml of water and 30 ml of dioxane a solution of 1.10 g of 3β,14β-dihydroxy-5β-androstane-17β-carboxaldehyde (Boutagy J. and Thomas R., Aust. J. Chem., 1971, 24, 2723) in 30 ml of dioxane was added dropwise at room temperature. After 2 hrs, the solution was evaporated to dryness under reduced pressure. The crude product was crystallized from ethanol/water and then from ethanol to give 0.60 g of the title compound (I-aa) as hydrobromide, white solid.
Reaction SMILES: CCN=C=NCCCN(C)C.[CH3:12][N:13]1[C:21]2[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=2)[C:15]([CH3:22])=[C:14]1[C:23]([OH:25])=O.C(Cl)Cl.[NH2:29][C@H:30]([C:34]([OH:36])=[O:35])[CH:31]([CH3:33])[CH3:32]>CN(C1C=CN=CC=1)C.CN(C=O)C>[CH3:12][N:13]1[C:21]2[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=2)[C:15]([CH3:22])=[C:14]1[C:23]([NH:29][C@H:30]([C:34]([OH:36])=[O:35])[CH:31]([CH3:33])[CH3:32])=[O:25]
Reactant: CC(C)[C@H](N)C(=O)O
Reactant: Cc1c(C(=O)O)n(C)c2ccccc12
Agent: CCN=C=NCCCN(C)C
Agent: CN(C)c1ccncc1
Solvent: ClCCl
Solvent: CN(C)C=O
Product: Cc1c(C(=O)N[C@H](C(=O)O)C(C)C)n(C)c2ccccc12
Temperature: 0 °C
Reaction time: 1 h
Yield: 94.6 %

Procedure:
DMAP (367 mg, 3.0 mmol) and EDAC (748 mg, 3.9 mmol) were added as solids to a solution of 1,3-dimethylindole-2-carboxylic acid (568 mg, 3.3 mmol) in DMF (5 mL), and the resultant mixture was stirred for 10 minutes under a nitrogen atmosphere at 0° C. A methylene chloride solution of the methyl ester of valine (553 mg, 3.3 mmol, in 5 mL of methylene chloride) was added to the mixture, and the mixture was first stirred for one hour at 0° C. then for 5 hours at room temperature. The reaction mixture was partitioned between ethyl acetate and 5% KHSO4 solution and the aqueous solution was back-extracted with ethyl acetate. The combined ethyl acetate washes were in turn washed with 5% KHSO4 solution saturated sodium bicarbonate solution (2×) and brine, dried over sodium sulfate, and concentrated to give the title product as a yellow syrup (900 mg).
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]([N+:20]([O-])=O)[CH:5]=[C:6]2[C:11]=1[N:10]([CH2:12][CH2:13][CH:14]1[CH2:18][CH2:17][CH2:16][N:15]1[CH3:19])[CH2:9][CH2:8][CH2:7]2.[H][H]>O1CCCC1.C(O)C.[Pd]>[F:1][C:2]1[CH:3]=[C:4]([NH2:20])[CH:5]=[C:6]2[C:11]=1[N:10]([CH2:12][CH2:13][CH:14]1[CH2:18][CH2:17][CH2:16][N:15]1[CH3:19])[CH2:9][CH2:8][CH2:7]2
Reactant: CN1CCCC1CCN1CCCc2cc([N+](=O)[O-])cc(F)c21
Reactant: [H][H]
Agent: [Pd]
Solvent: CCO
Solvent: C1CCOC1
Product: CN1CCCC1CCN1CCCc2cc(N)cc(F)c21
Reaction time: 4 h
Yield: 99.1 %

Procedure:
To a stirred solution of 8-fluoro-1-(2-(1-methylpyrrolidin-2-yl)ethyl)-6-nitro-1,2,3,4-tetrahydroquinoline (660 mg, 2.147 mmol) in tetrahydrofuran (6 ml) and ethanol (6.00 ml) was added palladium on carbon, 10 wt % (229 mg, 0.215 mmol). The suspension was stirred under balloon pressure of hydrogen and monitored by TLC. After 4 h, the reaction was complete. The mixture was then filtered through a pad of celite which was washed with methanol. The filtrate was then concentrated and dried on a high vacuum pump. The residue (8-fluoro-1-(2-(1-methylpyrrolidin-2-yl)ethyl)-1,2,3,4-tetrahydroquinolin-6-amine (590 mg, 2.127 mmol, 99% yield)) was used directly in the subsequent reaction. 1H NMR (DMSO-d6) δ 6.16 (dd, J=14.7, 2.4 Hz, 1H); 6.04 (m, 1H), 4.70 (brs, 1H), 2.99-2.93 (m, 3H), 2.88-2.82 (m, 2H), 2.57-2.53 (m, 2H), 2.24 (s, 3H), 2.15-2.05 (m, 2H); 1.93-1.87 (m, 2H), 1.69-1.60 (m, 4H), 1.44-1.35 (m, 2H).
Reaction SMILES: Cl[C:2]1[CH:11]=[CH:10][CH:9]=[CH:8][C:3]=1[CH2:4][CH2:5][CH:6]=[O:7].[CH:12]1(/[CH:18]=[CH:19]/[C:20](=[O:26])[C:21]([O:23][CH2:24][CH3:25])=[O:22])[CH2:17][CH2:16][CH2:15][CH2:14][CH2:13]1>C(Cl)(Cl)Cl>[CH2:4]([C@@H:5]1[C:6](=[O:7])[O:26][C:20]([C:21]([O:23][CH2:24][CH3:25])=[O:22])=[CH:19][C@@H:18]1[CH:12]1[CH2:17][CH2:16][CH2:15][CH2:14][CH2:13]1)[C:3]1[CH:8]=[CH:9][CH:10]=[CH:11][CH:2]=1
Reactant: O=CCCc1ccccc1Cl
Reactant: CCOC(=O)C(=O)/C=C/C1CCCCC1
Solvent: ClC(Cl)Cl
Product: CCOC(=O)C1=C[C@H](C2CCCCC2)[C@H](Cc2ccccc2)C(=O)O1
Yield: 85 %

Procedure:
Prepared according to the general procedure from 2-chloro-hydrocinnamaldehyde and (E)-ethyl 4-cyclohexyl-2-oxobut-3-enoate using 2 mol % 1 as the catalyst in 85% yield as a single diastereomer (colorless oil). [α]D20 (c 1.20, CHCl3)=+83.5; 1H NMR (400 MHz, CDCl3) δ 7.33-7.21 (m, 5H), 6.48 (d, 1H, J=6.5 Hz), 4.30 (dq, 1H, J=7.2, 1.8 Hz), 3.38 (dd, 1H, J=14.3, 5.7 Hz), 2.97-2.91 (m, 1H), 2.77 (dd, 1H, J=14.3, 9.1 Hz), 2.45-2.41 (m, 1H), 1.76-1.62 (m, 5H), 1.47-1.44 (m, 1H), 1.34 (t, 3H, J=7.2 Hz), 1.27-1.06 (m, 4H), 0.93-0.89 (m, 1H); 13C NMR (100 MHz, CDCl3) δ 170.4, 160.7, 142.8, 138.6, 128.9, 126.9, 117.6, 62.0, 43.0, 39.4, 37.7, 31.7, 31.4, 27.2, 26.8, 26.1, 14.3; IR (thin film) ν 3520, 3086, 3028, 2981, 2928, 2853, 1770, 1731, 1660, 1453, 1369, 1309, 1262, 1120, 1094, 1013 cm−1; HRMS (ESI) calcd for C21H26O4 [M+Na]+ 365.1723, found 365.1721; 95% ee (4S,5S)-isomer as determined by HPLC (AS-H, 20:1 hexanes/i-PrOH), tr (4S,5S)=19.1 min, tr (4R,5R)=15.7 min.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([C:8]([C:10]2[CH:19]=[CH:18][CH:17]=[C:16]3[C:11]=2[NH:12][CH2:13][CH2:14][NH:15]3)=[O:9])[CH:5]=[CH:6][CH:7]=1.N1C=CC=CC=1.[C:26](Cl)([O:28][CH2:29][C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1)=[O:27]>C(Cl)Cl>[Cl:1][C:2]1[CH:3]=[C:4]([CH:5]=[CH:6][CH:7]=1)[C:8]([C:10]1[CH:19]=[CH:18][CH:17]=[C:16]2[C:11]=1[NH:12][CH2:13][CH2:14][N:15]2[C:26]([O:28][CH2:29][C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1)=[O:27])=[O:9]
Reactant: O=C(c1cccc(Cl)c1)c1cccc2c1NCCN2
Reactant: O=C(Cl)OCc1ccccc1
Solvent: ClCCl
Solvent: c1ccncc1
Product: O=C(c1cccc(Cl)c1)c1cccc2c1NCCN2C(=O)OCc1ccccc1
Temperature: 25 °C
Reaction time: 3 h
Yield: 80 %

Procedure:
To a solution of (3-chlorophenyl)(1,2,3,4-tetrahydroquinoxalin-5-yl)methanone (50 g, 183 mmol) in DCM (200 mL) at 0° C. was added pyridine (17.79 mL, 220 mmol). Then CBZ—Cl (26.2 mL, 183 mmol) in DCM (1.0 mL) was added dropwise. The reaction mixture was warmed up to room temperature and stirred at room temperature for 3 h. The reaction mixture was washed with H2O, saturated NaHCO3, and brine, dried over Na2SO4, filtered, concentrated to give crude material. This crude material was purified via BIOTAGE®, eluted with 10% EtOAC/hexane to afford benzyl 5-(3-chlorobenzoyl)-3,4-dihydroquinoxaline-1(2H)-carboxylate, Intermediate E-1D (60 g, 147 mmol, 80% yield). 1H NMR (400 MHz, CDCl3) δ ppm 8.5 (1H, bs), 7.6 (1H, s), 7.45 (2H, m), 7.4 (7H, m), 7.25 (1H, m), 6.5 (1H, m), 5.2 (2H, m), 3.9 (2H, m), 3.6 (2H, m).
Reaction SMILES: [NH:1]1[CH:9]=[C:7]([CH3:8])[C:5](=[O:6])[NH:4][C:2]1=[O:3].C(=O)([O-])[O-].[K+].[K+].Br[CH2:17][C:18]([O:20]C)=[O:19]>CN(C=O)C>[C:18]([CH2:17][N:1]1[CH:9]=[C:7]([CH3:8])[C:5](=[O:6])[NH:4][C:2]1=[O:3])([OH:20])=[O:19]
Reactant: COC(=O)CBr
Reactant: Cc1c[nH]c(=O)[nH]c1=O
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: Cc1cn(CC(=O)O)c(=O)[nH]c1=O
Temperature: 0 °C
Reaction time: 8 h

Procedure:
This procedure is different from the literature synthesis, but is easier, gives higher yields, and leaves no unreacted thymine in the product. To a suspension of thymine (3, 40 g, 0.317 mol) and potassium carbonate (87.7 g, 0.634 mmol) in DMF (900 mL) was added methyl bromoacetate (30 mL, 0.317 mmol). The mixture was stirred vigorously overnight under nitrogen. The mixture was filtered and evaporated to dryness, in vacuo. The solid residue was treated with water (300 mL) and 4N hydrochloric acid (12 mL), stirred for 15 minutes at 0° C., filtered, and washed with water (2×75 mL). The precipitate was treated with water (120 mL) and 2N sodium hydroxide (60 mL), and was refluxed for 10 minutes. The mixture was cooled to 0° C., filtered, and title compound was precipitated by the addition of 4N hydrochloric acid (70 mL). The yield after drying, in vacuo over sicapent was 37.1 g (64%). 1H-NMR: (90 MHz; DMSO-d6): 11.33 ppm (s, 1H, NH); 7.49 (d, J=0.92 Hz, 1H, ArH); 4.38 (s, 2H, CH2); 1.76 (d, J=0.92 Hz, T-CH3).
Reaction SMILES: [CH3:1][O:2][C:3]1[C:15]([N+:16]([O-:18])=[O:17])=[CH:14][C:6]2[N:7]([CH3:13])[C:8](=[O:12])[CH2:9][NH:10][CH2:11][C:5]=2[CH:4]=1.Br[CH2:20][C:21]#N.C(N(CC)C(C)C)(C)C.CN(C)C=O>[I-].[Na+]>[CH2:20]([N:10]1[CH2:11][C:5]2[CH:4]=[C:3]([O:2][CH3:1])[C:15]([N+:16]([O-:18])=[O:17])=[CH:14][C:6]=2[N:7]([CH3:13])[C:8](=[O:12])[CH2:9]1)[CH3:21]
Reactant: N#CCBr
Reactant: COc1cc2c(cc1[N+](=O)[O-])N(C)C(=O)CNC2
Agent: [I-]
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: CCN(C(C)C)C(C)C
Product: CCN1CC(=O)N(C)c2cc([N+](=O)[O-])c(OC)cc2C1
Yield: 91.3 %

Procedure:
A mixture of 7-Methoxy-1-methyl-8-nitro-1,3,4,5-tetrahydro-benzo[e][1,4]diazepin-2-one (0.50 g, 0.0020 mol), Sodium iodide (0.0148 g, 0.0000987 mol), Bromoacetonitrile (0.276 mL, 0.00396 mol) and N,N-Diisopropylethylamine (1.04 mL, 0.00597 mol) in N,N-Dimethylformamide (6 mL, 0.08 mol) was reacted in an analogous manner to example 736-E to give 4-Ethyl-7-methoxy-1-methyl-8-nitro-1,3,4,5-tetrahydro-benzo[e][1,4]diazepin-2-one as a tan solid (0.51 g, 88%). Mp129-131° C.; LCMS (m/e) 291 (M+1); 1H-NMR (DMSO, 400 MHz) δ 7.96 (s, 1H), 7.51 (s, 1H), 3.93-92 (s, 3H), 3.86 (s, 2H), 3.82 (s, 2H), 3.27 (s, 3H), 3.16 (s, 2H).
Reaction SMILES: [Li+].[Cl-].C([Sn](CCCC)(CCCC)[CH:8]=[CH:9][C:10]1[CH:11]=[C:12]2[C:17](=[CH:18][CH:19]=1)[CH:16]=[C:15]([C:20]#[N:21])[CH:14]=[CH:13]2)CCC.[CH3:30][N:31]([CH:33]=O)C>C(OCC)(=O)C.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[CH:14]([C:30]1[C:11]2[C:10](=[CH:19][CH:18]=[C:17]([CH:8]=[CH:9][C:10]3[CH:11]=[C:12]4[C:17](=[CH:18][CH:19]=3)[CH:16]=[C:15]([C:20]#[N:21])[CH:14]=[CH:13]4)[CH:12]=2)[CH2:9][CH2:33][N:31]=1)([CH3:15])[CH3:13]
Reactant: CCCC[Sn](C=Cc1ccc2cc(C#N)ccc2c1)(CCCC)CCCC
Reactant: CN(C)C=O
Agent: Cl[Pd](Cl)([P](c1ccccc1)(c1ccccc1)c1ccccc1)[P](c1ccccc1)(c1ccccc1)c1ccccc1
Agent: [Cl-]
Agent: [Li+]
Solvent: CCOC(C)=O
Product: CC(C)C1=NCCc2ccc(C=Cc3ccc4cc(C#N)ccc4c3)cc21
Temperature: 80 °C
Reaction time: 1.75 h

Procedure:
A solution of Example 13I (70 mg, 0.23 mmol), dichlorobis(triphenylphosphine)palladium (II) (7.0 mg, 0.01 mmol), and LiCl (31 mg, 0.73 mmol) in DMF (1.7 mL) was treated dropwise with a solution of Example 13E (120 mg, 0.26 mmol) in DMF (0.2 mL). The mixture was heated to 80° C., stirred for 1.75 hours, cooled to room temperature, diluted with ethyl acetate, washed with H2O and brine, dried (MgSO4), filtered, and concentrated. The concentrate was purified by flash column chromatography on silica gel with 30% ethyl acetate/hexanes to provide the desired product.
Reaction SMILES: [CH3:1][C:2](=[CH:6][CH2:7][CH:8]1[CH2:12][CH:11]=[C:10]([CH3:13])[C:9]1([CH3:15])[CH3:14])[C:3](=[O:5])[CH3:4].[I-].[CH3:17][S+](C)(C)=O.[H-].[Na+]>>[CH3:1][C:2]1([C:3](=[O:5])[CH3:4])[CH2:17][CH:6]1[CH2:7][CH:8]1[CH2:12][CH:11]=[C:10]([CH3:13])[C:9]1([CH3:15])[CH3:14]
Reactant: CC(=O)C(C)=CCC1CC=C(C)C1(C)C
Reactant: C[S+](C)(C)=O
Agent: [H-]
Agent: [I-]
Agent: [Na+]
Product: CC(=O)C1(C)CC1CC1CC=C(C)C1(C)C
Yield: 44.6 %

Procedure:
11.3 g (55 mmol) of 3-methyl-5(2,2,3-trimethylcyclopent-3enyl)-pent-3-en-2-one was cyclopropanated with 14.1 g (63 mmol) of trimethylsulfoxonium iodide and 3.08 g (64 mmol) of 50% oil suspension of sodium hydride according to Example 11a giving 5.4 g (45% yield) of 1-[1-methyl-2(2,2,3trimethylcyclopent-3-enylmethyl)cyclopropyl]ethanone.
Reaction SMILES: [NH2:1][CH2:2][C:3]([OH:5])=[O:4].[Cl:6][C:7]1[C:19]([Cl:20])=[C:18](/[CH:21]=[C:22](/[N+:25]([O-:27])=[O:26])\[CH2:23][CH3:24])[CH:17]=[CH:16][C:8]=1[O:9][CH2:10][CH2:11][CH2:12][C:13](Cl)=[O:14]>O1CCCC1>[Cl:6][C:7]1[C:19]([Cl:20])=[C:18](/[CH:21]=[C:22](/[N+:25]([O-:27])=[O:26])\[CH2:23][CH3:24])[CH:17]=[CH:16][C:8]=1[O:9][CH2:10][CH2:11][CH2:12][C:13]([NH:1][CH2:2][C:3]([OH:5])=[O:4])=[O:14]
Reactant: NCC(=O)O
Reactant: CC/C(=C\c1ccc(OCCCC(=O)Cl)c(Cl)c1Cl)[N+](=O)[O-]
Solvent: C1CCOC1
Product: CC/C(=C\c1ccc(OCCCC(=O)NCC(=O)O)c(Cl)c1Cl)[N+](=O)[O-]
Temperature: 25 °C
Reaction time: 2.25 h

Procedure:
To a stirring suspension of finely ground glycine (6.01 g, 0.08 mole) in tetrahydrofuran (50 ml) is added, dropwise, the solution of E-4-[2,3-dichloro-4-(2-nitro-1-butenyl)phenoxy]butyryl chloride over a period of 15 minutes. The mixture is stirred at ambient temperature for 2.25 hours and then at reflux for one hour. The mixture is cooled, filtered and washed with tetrahydrofuran. The solid is suspended in water (60 ml), filtered, washed with water and dried to give 7.45 g of N-{(E)-4-[2,3-dichloro-4-(2-nitro-1-butenyl)phenoxy]butyryl}glycine.
Reaction SMILES: N[C:2]1[S:3][C:4]([C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=2)=[N:5][N:6]=1.N([O-])=O.[Na+].[ClH:17]>C(O)(=O)C.O.[Cu]>[Cl:17][C:2]1[S:3][C:4]([C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=2)=[N:5][N:6]=1
Reactant: Nc1nnc(-c2ccccc2)s1
Reactant: Cl
Agent: [Cu]
Agent: O=N[O-]
Agent: [Na+]
Solvent: O
Solvent: CC(=O)O
Product: Clc1nnc(-c2ccccc2)s1
Temperature: 0 °C
Reaction time: 4 h

Procedure:
A stirred suspension of 2-amino-5-phenyl-[1,3,4]thiadiazole (6.45 g, 36.4 mmol; Aldrich) and copper (230 mg, 3.6 mmol; Aldrich) in hydrochloric acid (36 mL, 12 M) and glacial acetic acid (180 mL) was chilled to 0° C. and treated with a solution of sodium nitrite (2.64 g, 38.2 mmol; Aldrich) in water (12 mL), added dropwise over 40 minutes. After stirring at room temperature for 4 hours, the mixture was poured into ice water. The aqueous solution was extracted with chloroform (3×), and the combined extracts were washed sequentially with 5% sodium bicarbonate and brine, and dried over sodium sulfate. The crude product was filtered through a short silica gel plug with chloroform to afford the title product: 1H NMR (300 MHz, CDCl3) δ ppm 7.46-7.55 (m, 3H), 7.85-7.93 (m, 2H) MS (DCI/NH3) m/e 197/199 (M+H)+.
Reaction SMILES: [CH:1]1[C:10]2[C:5](=[CH:6][C:7]([C:11]([O:13][CH3:14])=[O:12])=[CH:8][CH:9]=2)[CH:4]=[CH:3][C:2]=1[C:15]([O:17][CH3:18])=[O:16].C(O)[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][CH3:36].CO>C(O)(C)C>[CH:6]1[C:5]2[C:10](=[CH:1][C:2]([C:15]([O:17][CH2:18][CH2:36][CH2:35][CH2:34][CH2:33][CH2:32][CH2:31][CH2:30][CH2:29][CH2:28][CH2:27][CH2:26][CH2:25][CH2:24][CH2:23][CH2:22][CH2:21][CH3:20])=[O:16])=[CH:3][CH:4]=2)[CH:9]=[CH:8][C:7]=1[C:11]([O:13][CH2:14][CH2:36][CH2:35][CH2:34][CH2:33][CH2:32][CH2:31][CH2:30][CH2:29][CH2:28][CH2:27][CH2:26][CH2:25][CH2:24][CH2:23][CH2:22][CH2:21][CH3:20])=[O:12]
Reactant: COC(=O)c1ccc2cc(C(=O)OC)ccc2c1
Reactant: CCCCCCCCCCCCCCCCCCO
Solvent: CO
Solvent: CC(C)O
Product: CCCCCCCCCCCCCCCCCCOC(=O)c1ccc2cc(C(=O)OCCCCCCCCCCCCCCCCCC)ccc2c1
Temperature: 160 °C
Yield: 85.8 %

Procedure:
To a 3 neck 100 mL round bottomed flask equipped with a Dean Stark trap and condenser, thermocouple and argon inlet was added dimethyl naphthalene-2,6-dicarboxylate (10 grams, 40.94 mmoles, available from Sigma Aldrich), stearyl alcohol (22.15 grams, 81.89 mmoles, available from Spectrum Chemical), Fascat 4100 (0.03 grams, 0.1 wt %, available from Arkema Inc) and Xylenes (50 ml, available from Sigma Aldrich). The mixture was slowly heated under argon to 160° C. during which reagents melted/dissolved. The temperature was raised to 180° C. The reaction mixture was stirred at 180° C. overnight (˜20 hours) during which 46 mL of a mixture of xylenes and methanol was collected. Vacuum was applied (1-2 mm-Hg) for about 10 minutes during which an additional 5 mL of a mixture of Xylenes and methanol was collected. The solution was cooled under argon to about 140° C. and discharged in an aluminum tray where it was allowed to cool to room temperature to give product as an off-white solid. The product was transferred to a 1 L Erlenmeyer flask, about 100 mL of isopropyl alcohol was added, heated to about 100° C. during which product dissolved. The solution was cooled to room temperature during which product crystallized out, filtered and dried on a vacuum pump overnight to give 25.33 grams product as an off-white solid (86% yield). The product was shown to be pure by 1H NMR with trace amounts of the mono-ester. Physical properties of this compound are shown in Table 2 above. The FIGURE shows the rheological profile.
Reaction SMILES: [CH3:1][C:2]1[N:3]([S:13]([C:16]2[CH:22]=[CH:21][C:19]([CH3:20])=[CH:18][CH:17]=2)(=[O:15])=[O:14])[C:4]2[C:9]([C:10]=1[CH2:11]O)=[CH:8][CH:7]=[CH:6][CH:5]=2.S(Cl)([Cl:25])=O>C(Cl)(Cl)Cl>[Cl:25][CH2:11][C:10]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[N:3]([S:13]([C:16]2[CH:17]=[CH:18][C:19]([CH3:20])=[CH:21][CH:22]=2)(=[O:14])=[O:15])[C:2]=1[CH3:1]
Reactant: Cc1ccc(S(=O)(=O)n2c(C)c(CO)c3ccccc32)cc1
Reactant: O=S(Cl)Cl
Solvent: ClC(Cl)Cl
Product: Cc1ccc(S(=O)(=O)n2c(C)c(CCl)c3ccccc32)cc1
Reaction time: 0.17 h
Yield: 103.6 %

Procedure:
To a stirred solution of (2-methyl-1-tosyl-1H-indol-3-yl)methanol (500 mg, 1.59 mmol) in chloroform (20 mL), thionyl chloride (0.23 mL, 3.18 mmol) was added dropwise at 0° C. and stirred for 10 min. Then the mixture was heated under reflux for 3.5 h. The reaction mixture was concentrated under reduced pressure. The residue was taken up in diethyl ether and evaporated to dryness under reduced pressure to yield the title compound (550 mg, quant.). The compound was directly used for the next step without further purification. [TLC Rf=0.58 (ethyl acetate/hexane 20:80)].
Reaction SMILES: [OH:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:13]=[CH:12][C:11]([CH:14]=O)=[CH:10][CH:9]=2)=[CH:4][CH:3]=1.Cl.[NH2:17][OH:18]>>[OH:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:13]=[CH:12][C:11]([CH:14]=[N:17][OH:18])=[CH:10][CH:9]=2)=[CH:4][CH:3]=1
Reactant: NO
Reactant: O=Cc1ccc(-c2ccc(O)cc2)cc1
Agent: Cl
Product: ON=Cc1ccc(-c2ccc(O)cc2)cc1

Procedure:
The title compound was prepared by reacting 4′-hydroxy[1,1′-biphenyl]-4-carbaldehyde (1.03 mmol) with hydroxylamine hydrochloride (140 mg, 2 mmol) according to Method C to yield 193 mg (79%, over two steps) of yellowish solid: mp 207-210° C.; 1H NMR (DMSO-d6): δ 6.85 (2H, d, J=8.37 Hz), 7.53 (2H, d, J=8.39 Hz), 7.62 (4H, s), 8.15 (1H, s), 9.62 (1H, s), 11.21 (1H, s); MS (ESI) m/z 212 (M−H)−.
Reaction SMILES: [CH3:1][C:2]1([CH3:15])[CH:7]=[CH:6][CH:5]=[C:4]([C:8](=[O:14])[CH2:9][CH:10](C)[CH:11]=[CH2:12])[CH2:3]1.CC1(C)CC=C[C:19]([C:23](=[O:29])CC(C)C=C)=C1>>[CH3:15][C:2]1([CH3:1])[CH2:7][CH2:6][CH:5]=[C:4]([C:8]2([O:14][CH2:19][CH2:23][O:29]2)[CH2:9][CH2:10][CH:11]=[CH2:12])[CH2:3]1
Reactant: C=CC(C)CC(=O)C1=CC=CC(C)(C)C1
Reactant: C=CC(C)CC(=O)C1=CC(C)(C)CC=C1
Product: C=CCCC1(C2=CCCC(C)(C)C2)OCCO1

Procedure:
##STR8## 1-(3,3-Dimethyl-cyclohexa-4,6-dien-1-yl)-3-methyl-pent-4-en-1-one and 1-(3,3-dimethyl-cyclohexa-1,5-dien-1-yl)-3-methyl-pent-4-en-1-one
Reaction SMILES: [CH:1]([C:4]1[CH:9]=[CH:8][C:7]([C:10]2[N:15]=[C:14]([C:16]3[CH:17]=[C:18]([CH:24]=[CH:25][CH:26]=3)[C:19]([O:21]CC)=[O:20])[CH:13]=[CH:12][CH:11]=2)=[CH:6][CH:5]=1)([CH3:3])[CH3:2].O.[OH-].[Li+].Cl>CO>[CH:1]([C:4]1[CH:5]=[CH:6][C:7]([C:10]2[N:15]=[C:14]([C:16]3[CH:17]=[C:18]([CH:24]=[CH:25][CH:26]=3)[C:19]([OH:21])=[O:20])[CH:13]=[CH:12][CH:11]=2)=[CH:8][CH:9]=1)([CH3:3])[CH3:2]
Reactant: CCOC(=O)c1cccc(-c2cccc(-c3ccc(C(C)C)cc3)n2)c1
Agent: Cl
Agent: [Li+]
Agent: [OH-]
Solvent: O
Solvent: CO
Product: CC(C)c1ccc(-c2cccc(-c3cccc(C(=O)O)c3)n2)cc1
Yield: 84.7 %

Procedure:
Part C. A solution of ethyl 3-[6-(4-isopropyl-phenyl)-pyridin-2-yl]-benzoate (90 mg) in 3 mL methanol-1 mL water is treated with lithium hydroxide hydrate (50 mg). The solution is heated to between 40 and 50° C. for 12 h. with stirring, then cooled and neutralized to pH 7 with 3 N aq. HCl. The mixture is extracted with ethyl acetate, and the extract is washed with brine, dried over sodium sulfate, filtered and evaporated to afford the title product as a powder (70 mg, 85%), m.p. 215-216° C. NMR (300 MHz, CDCl3): δ 8.86 (1H, s), 8.47 (1H, d, J=8 Hz), 8.18 (1H, d, J=8 Hz), 8.08 (2H, d, J=9 Hz), 7.85 (1H, t, J=7 Hz), 7.77 (1H, d, J=7 Hz), 7.76 (1H, d, J=7 Hz), 7.62 (1H, t, J=8 Hz), 7.38 (2H, d, J=9 Hz), 2.99 (1H, heptet, J=7 Hz), 1.30 (6H, d, J=7 Hz). MS (ES+): m/e 319 (20), 318 (100).
Reaction SMILES: [CH3:1][O:2][CH:3]([O:15][CH3:16])[C:4]1[C:9](Br)=[CH:8][C:7]([O:11][CH3:12])=[C:6]([O:13][CH3:14])[CH:5]=1.[CH:17](=[O:19])[CH3:18]>>[CH3:1][O:2][CH:3]([O:15][CH3:16])[C:4]1[C:9]([CH:17]([OH:19])[CH3:18])=[CH:8][C:7]([O:11][CH3:12])=[C:6]([O:13][CH3:14])[CH:5]=1
Reactant: CC=O
Reactant: COc1cc(Br)c(C(OC)OC)cc1OC
Product: COc1cc(C(C)O)c(C(OC)OC)cc1OC

Procedure:
6-Bromo-3,4-dimethoxybenzaldehyde dimethylacetal and acetaldehyde are treated in the same manner as in Reference Example 3 to give 3,4-dimethoxy-6-(1-hydroxyethyl)benzaldehyde dimethylacetal as oil.
Reaction SMILES: [Br:1][CH:2]([C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1)[C:3]([OH:5])=O.[NH2:12][CH2:13][C:14]1[CH:21]=[CH:20][C:17]([C:18]#[N:19])=[CH:16][CH:15]=1>>[Br:1][CH:2]([C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1)[C:3]([NH:19][CH2:18][C:17]1[CH:20]=[CH:21][C:14]([C:13]#[N:12])=[CH:15][CH:16]=1)=[O:5]
Reactant: N#Cc1ccc(CN)cc1
Reactant: O=C(O)C(Br)c1ccccc1
Product: N#Cc1ccc(CNC(=O)C(Br)c2ccccc2)cc1

Procedure:
α-Bromophenylacetic acid was reacted with 4-aminomethyl benzonitrile according to general procedure C to give (RS)-2-bromo-N-(4-cyano-benzyl)-2-phenyl-acetamide. White solid. MS 329.1 ([M+H]+)
Reaction SMILES: CS([CH2:5][CH:6]=[CH:7][CH2:8]S(C)(=O)=O)(=O)=O.[CH3:13][O:14][C:15]1[CH:22]=[CH:21][C:18]([CH2:19][NH2:20])=[CH:17][CH:16]=1>ClCCl>[CH3:13][O:14][C:15]1[CH:22]=[CH:21][C:18]([CH2:19][N:20]2[CH2:8][CH:7]=[CH:6][CH2:5]2)=[CH:17][CH:16]=1
Reactant: CS(=O)(=O)CC=CCS(C)(=O)=O
Reactant: COc1ccc(CN)cc1
Solvent: ClCCl
Product: COc1ccc(CN2CC=CC2)cc1
Temperature: 25 °C
Reaction time: 20 h
Yield: 63.6 %

Procedure:
To a solution of 1,4-dimethylsulphonyl-2-butene (2.15 g, 11.64 mmol) in dichloromethane (40 ml), 4-methoxybenzylamine (6 ml, 44.24 mmol) was added dropwise and the solution was stirred 20 hours at r.t. The solid was filtrated and the filtrate was washed with water (2×30 ml), dried over Na2SO4, filtered and concentrated. The crude was purified by flash chromatography: silica gel, gradient hexane:ethyl acetate 3:1 to 1:1. to afforded the product (1.4 g, 63%) as yellow oil.
Reaction SMILES: [C:1](=[O:23])([O:20][CH2:21][CH3:22])[O:2][C:3]1[CH:8]=[CH:7][C:6]([CH3:9])=[CH:5][C:4]=1[CH:10]1[CH:17]2[CH2:18][CH:13]3[CH2:14][CH:15]([CH2:19][CH:11]1[CH2:12]3)[CH2:16]2.[N+:24]([O-])([O-:26])=[O:25].[K+]>OS(O)(=O)=O>[C:1](=[O:23])([O:20][CH2:21][CH3:22])[O:2][C:3]1[CH:8]=[C:7]([N+:24]([O-:26])=[O:25])[C:6]([CH3:9])=[CH:5][C:4]=1[CH:10]1[CH:11]2[CH2:19][CH:15]3[CH2:14][CH:13]([CH2:18][CH:17]1[CH2:16]3)[CH2:12]2
Reactant: CCOC(=O)Oc1ccc(C)cc1C1C2CC3CC(C2)CC1C3
Reactant: O=[N+]([O-])[O-]
Agent: O=S(=O)(O)O
Agent: [K+]
Product: CCOC(=O)Oc1cc([N+](=O)[O-])c(C)cc1C1C2CC3CC(C2)CC1C3
Temperature: 25 °C
Reaction time: 3 h
Yield: 25 %

Procedure:
To a cooled solution of 2-admantyl-4-methyl-phenyl ethyl carbonate (1.32 g, 4.2 mmol) in H2SO4 (98%, 10 mL) was added KNO3 (510 mg, 5.0 mmol) in small portions at 0° C. The mixture was stirred for 3 h while warming to room temperature, poured into ice and then extracted with dichloromethane. The combined organic layers were washed with NaHCO3 and brine, dried over MgSO4 and concentrated to dryness. The residue was purified by column chromatography (0-10% EtOAc-Hexane) to yield 2-admantyl-4-methyl-5-nitrophenyl ethyl carbonate (378 mg, 25%).