Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [N:1]1[CH:6]=[CH:5][C:4]([CH:7]([NH:9][CH:10]=[O:11])[CH3:8])=[CH:3][CH:2]=1.[H][H]>C(O)(=O)C>[NH:1]1[CH2:6][CH2:5][CH:4]([CH:7]([NH:9][CH:10]=[O:11])[CH3:8])[CH2:3][CH2:2]1
Reactant: [H][H]
Reactant: CC(NC=O)c1ccncc1
Solvent: CC(=O)O
Product: CC(NC=O)C1CCNCC1

Procedure:
N-(1-Pyridin-4-yl-ethyl)-formamide (1.86 g, 12.38 mmol) was dissolved in 50 ml of acetic acid. After addition of Rh (5% on Al2O3, 307 mg) the mixture was hydrogenated with 10 bar hydrogen and 100° C. for 120 hours. The mixture was evaporated and lyophilised. The crude material was used without purification.
Reaction SMILES: [H-].[Al+3].[Li+].[H-].[H-].[H-].[CH3:7][O:8][C:9]1[CH:10]=[C:11]([CH2:16][CH2:17][C:18](O)=[O:19])[CH:12]=[CH:13][C:14]=1[CH3:15].OS(O)(=O)=O>C1COCC1>[CH3:7][O:8][C:9]1[CH:10]=[C:11]([CH2:16][CH2:17][CH2:18][OH:19])[CH:12]=[CH:13][C:14]=1[CH3:15]
Reactant: COc1cc(CCC(=O)O)ccc1C
Agent: O=S(=O)(O)O
Agent: [Al+3]
Agent: [H-]
Solvent: C1CCOC1
Product: COc1cc(CCCO)ccc1C
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 91.4 %

Procedure:
A suspension of 3.3 g (98.1 mmol) of lithium aluminum hydride in 40 mL THF was treated dropwise with a solution of 8.65 g (44.5 mmol) of 3-(3-methoxy-4-methylphenyl)propanoic acid in 125 mL of THF. After stirring at room temperature for 0.5 hour, the mixture was heated at reflux for 2 hours. The mixture was cautiously acidified with 1N H2SO4, then extracted with EtOAc. The EtOAc was washed with 1N H2SO4, H2O, saturated NaHCO3, and saturated NaCl. Drying over MgSO4 and removal of the solvent under reduced pressure left 7.33 g (91.6% yield) of the product as a clear oil. The structure was confirmed by NMR and mass spectroscopy. MS m/z 181 (M+H+).
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]([CH:8]=[CH:9][C:10](=[O:12])[CH3:11])[CH:5]=[CH:6][CH:7]=1.C[O:14][C:15]1C=CC=C[C:16]=1C1CC(=O)CC(=O)C1>>[F:1][C:2]1[CH:3]=[C:4]([CH:8]2[CH2:16][C:15](=[O:14])[CH2:11][C:10](=[O:12])[CH2:9]2)[CH:5]=[CH:6][CH:7]=1
Reactant: CC(=O)C=Cc1cccc(F)c1
Reactant: COc1ccccc1C1CC(=O)CC(=O)C1
Product: O=C1CC(=O)CC(c2cccc(F)c2)C1

Procedure:
The title compound was prepared from 4-(3-fluoro-phenyl)-but-3-en-2-one stage 1 (940 mg, 5.73 mmol), following the procedure describing the synthesis of 5-(2-methoxy-phenyl)-cyclohexane-1,3-dione (example 1/a stage 2).
Reaction SMILES: [NH:1]([C:5]1[S:6][CH:7]=[C:8]([C:10]2[O:11][C:12]([C:15](=O)[N:16]([CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH3:23])[CH3:17])=[CH:13][CH:14]=2)[N:9]=1)[C:2]([NH2:4])=[NH:3].B#B.Cl.[OH-].[Na+]>O1CCCC1>[NH:1]([C:5]1[S:6][CH:7]=[C:8]([C:10]2[O:11][C:12]([CH2:15][N:16]([CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH3:23])[CH3:17])=[CH:13][CH:14]=2)[N:9]=1)[C:2]([NH2:4])=[NH:3]
Reactant: CCCCCCN(C)C(=O)c1ccc(-c2csc(NC(=N)N)n2)o1
Agent: B#B
Agent: Cl
Agent: [Na+]
Solvent: C1CCOC1
Product: CCCCCCN(C)Cc1ccc(-c2csc(NC(=N)N)n2)o1

Procedure:
2-Guanidino-4-(5-[N-n-hexyl-N-methylcarbamoyl]-2-furyl)thiazole (2.0 g., 4 mmole) was reduced with an excess of diborane in tetrahydrofuran substantially according to the procedure of Example 1. At the end of the reduction, 15 ml. of 6N hydrochloric acid was added and the resulting mixture was heated under reflux for 25 minutes. The cooled mixture was then made alkaline with 10N sodium hydroxide solution and the solid which precipitated was removed by filtration. The remaining aqueous phase was extracted with n-butanol, and the extracts were dried (Na2SO4) and evaporated. The residue was purified by column chromatography on silica gel using 1:5 methanolchloroform as eluant, giving two crops of the title compound, 300 mg. and 460 mg.
Reaction SMILES: [CH3:1][C:2]1[CH:7]=[CH:6][C:5]([S:8]([O:11][CH2:12][CH:13]2[CH2:17][C:16]3[CH:18]=[CH:19][CH:20]=[C:21](Br)[C:15]=3[O:14]2)(=[O:10])=[O:9])=[CH:4][CH:3]=1.[Cl:23][C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=1B(O)O.C(=O)([O-])[O-].[K+].[K+]>CC1C=CC=CC=1[P](C1C=CC=CC=1C)([Pd](Cl)(Cl)[P](C1=C(C)C=CC=C1)(C1C=CC=CC=1C)C1C=CC=CC=1C)C1C=CC=CC=1C>[CH3:1][C:2]1[CH:7]=[CH:6][C:5]([S:8]([O:11][CH2:12][CH:13]2[CH2:17][C:16]3[CH:18]=[CH:19][CH:20]=[C:21]([C:25]4[CH:26]=[CH:27][CH:28]=[CH:29][C:24]=4[Cl:23])[C:15]=3[O:14]2)(=[O:10])=[O:9])=[CH:4][CH:3]=1
Reactant: OB(O)c1ccccc1Cl
Reactant: Cc1ccc(S(=O)(=O)OCC2Cc3cccc(Br)c3O2)cc1
Agent: Cc1ccccc1[P](c1ccccc1C)(c1ccccc1C)[Pd](Cl)(Cl)[P](c1ccccc1C)(c1ccccc1C)c1ccccc1C
Agent: O=C([O-])[O-]
Agent: [K+]
Product: Cc1ccc(S(=O)(=O)OCC2Cc3cccc(-c4ccccc4Cl)c3O2)cc1
Yield: 70.2 %

Procedure:
Treatment of (±)-(7-bromo-2,3-dihydro-1-benzofuran-2-yl)methyl 4-methylbenzenesulfonate (0.50 g, 1.305 mmol) with 2-chlorophenylboronic acid (0.306 g, 1.96 mmol), dichlorobis(tri-o-tolylphosphine)-palladium(II) (0.051 g, 0.065 mmol), and potassium carbonate (0.45 g, 3.26 mmol) generally according to the procedure described for Intermediate 37 provided 0.380 g (70%) of (±)-[7-(2-chlorophenyl)-2,3-dihydro-1-benzofuran-2-yl]methyl 4-methylbenzenesulfonate as a tan solid. mp 100-103° C.; Anal. calcd. for C22H19ClO4S: C, 63.69; H, 4.62. Found: C, 63.43; H, 4.69.
Reaction SMILES: [CH3:1][O:2][C:3]([C:5]1[CH:6]=[N:7][NH:8][CH:9]=1)=[O:4].[H-].[Na+].Cl[C:13]1[CH2:17][C:16]([C:22]2[CH:27]=[C:26]([Cl:28])[CH:25]=[C:24]([Cl:29])[CH:23]=2)([C:18]([F:21])([F:20])[F:19])[O:15][N:14]=1.N1C=CC=N1>C(#N)C>[CH3:1][O:2][C:3]([C:5]1[CH:6]=[N:7][N:8]([C:13]2[CH2:17][C:16]([C:22]3[CH:27]=[C:26]([Cl:28])[CH:25]=[C:24]([Cl:29])[CH:23]=3)([C:18]([F:19])([F:20])[F:21])[O:15][N:14]=2)[CH:9]=1)=[O:4]
Reactant: COC(=O)c1cn[nH]c1
Reactant: FC(F)(F)C1(c2cc(Cl)cc(Cl)c2)CC(Cl)=NO1
Agent: [H-]
Agent: [Na+]
Agent: c1cn[nH]c1
Solvent: CC#N
Product: COC(=O)c1cnn(C2=NOC(c3cc(Cl)cc(Cl)c3)(C(F)(F)F)C2)c1
Temperature: 25 °C
Reaction time: 1 h
Yield: 100.3 %

Procedure:
To a solution of pyrazole-4-carboxylic acid methyl ester (756 mg) in acetonitrile (30 ml) under argon was added sodium hydride (240 mg). The reaction mixture was stirred at room temperature for 1 h. 15 mf of this solution was added dropwise to a solution of chloroisoxazoline of example 17.2 (630 mg) in acetonitrile (10 ml). It was then stirred at room temperature for 1 h; 15 ml of pyrazole solution was added again and the mixture was stirred over the weekend. The reaction was quenched by adding water and dichloromethane. The two layers were separated. The aqueous layer was extracted with dichloromethane. The combined organic layers were washed with brine, dried over sodium sulfate and concentrated. The crude residue was purified by column chromatography (from c-Hex (100%) to c-Hex:EtOAc (80:20)) to afford the title intermediate (810 mg) as a yellow solid. 1H-NMR (CDCl3, 400 MHz): 8.60 (s, 1H), 8.10 (s, 1H), 7.5 (m, 2H), 7.45 (m, 1H), 4.35 (d, 1H), 4.00 (d, 1H), 3.75 (s, 3H).
Reaction SMILES: C([C@H]([C@@H](C(OC(C)C)=O)O)O)(OC(C)C)=[O:2].C(OO)(C)(C)C.[F:23][C:24]1[CH:25]=[C:26]([CH:31]=[CH:32][CH:33]=1)/[CH:27]=[CH:28]/[CH2:29][OH:30].[OH-].[Na+].[Cl-].[Na+]>ClCCl.CC(C)[O-].[Ti+4].CC(C)[O-].CC(C)[O-].CC(C)[O-].C(OCC)C>[F:23][C:24]1[CH:25]=[C:26]([C@H:27]2[O:2][C@@H:28]2[CH2:29][OH:30])[CH:31]=[CH:32][CH:33]=1
Reactant: CC(C)OC(=O)[C@@H](O)[C@H](O)C(=O)OC(C)C
Reactant: OC/C=C/c1cccc(F)c1
Agent: [Ti+4]
Agent: CC(C)(C)OO
Agent: CC(C)[O-]
Solvent: ClCCl
Solvent: CCOCC
Product: OC[C@H]1O[C@@H]1c1cccc(F)c1
Temperature: -25 °C
Reaction time: 0.17 h
Yield: 299.1 %

Procedure:
An oven-dried, 3-neck, 2-L round bottom flask fitted with two oven-dried addition funnels and a rubber septum was charged with diisopropyl D-tartrate (11.55 g, 49.3 mmol, 0.30 equiv.), 4 Å powdered, activated molecular sieves (40 g) and dry dichloromethane (800 mL) under nitrogen. After being cooled to −25° C., to the reaction mixture was added titanium isopropoxide (9.6 mL, 33 mmol, 0.20 equiv.) slowly via a hypodermic syringe. After stirring for 10 minutes, anhydrous t-butyl hydroperoxide (5.5 M in decane, 75.0 mL, 413 mmol, 2.5 equiv.) was added at a moderate rate via an addition funnel. The resulting mixture was stirred at −25° C. for 30 minutes. trans-3-Fluorocinnamyl alcohol (25.0 g, 164 mmol) in dry dichloromethane (50 mL) was added dropwise via an addition funnel while maintaining the temperature at −25° C. After the addition, the reaction mixture was stirred at −25° C. for 1 hour and at −20° C. for another 3 hours. After the reaction was complete, cooled aqueous sodium hydroxide solution (30%, 20 mL) saturated with sodium chloride was added slowly at −20° C. After diethyl ether (150 mL) was added, the cold bath was removed and the mixture was allowed to warm to ˜5° C. and stirred for 1 hour. Magnesium sulfate (anhydrous, 50 g) was added and the mixture was stirred for 20 minutes, then filtered through a pad of silica gel, and washed with ether (300 mL). The filtrate was concentrated and toluene was used to azeotropically remove excess t-butyl hydroperoxide. The residual oil was purified on silica gel (0-30% ethyl acetate:hexane) to give 24.80 g (90%) of [(2R,3R)-3-(3-fluorophenyl)oxiran-2-yl]methanol as a viscous, colorless oil. Percent ee: >96.5%. MS (ESI) m/z 169.1 ([M+H]+).
Reaction SMILES: [C:1]1([O:7][C:8](=[O:34])[N:9]([C:19]2[CH:24]=[C:23]([O:25][C:26]3[CH:31]=[CH:30][C:29]([NH2:32])=[C:28]([F:33])[CH:27]=3)[CH:22]=[CH:21][N:20]=2)[C:10]([O:12][C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)=[O:11])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[C:35]1([NH:41][C:42]([C:44]2([C:47](O)=[O:48])[CH2:46][CH2:45]2)=[O:43])[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1.C(N(CC)CC)C.F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1>CN(C)C=O>[C:1]1([O:7][C:8](=[O:34])[N:9]([C:19]2[CH:24]=[C:23]([O:25][C:26]3[CH:31]=[CH:30][C:29]([NH:32][C:47]([C:44]4([C:42](=[O:43])[NH:41][C:35]5[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=5)[CH2:45][CH2:46]4)=[O:48])=[C:28]([F:33])[CH:27]=3)[CH:22]=[CH:21][N:20]=2)[C:10]([O:12][C:13]2[CH:14]=[CH:15][CH:16]=[CH:17][CH:18]=2)=[O:11])[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1
Reactant: O=C(O)C1(C(=O)Nc2ccccc2)CC1
Reactant: Nc1ccc(Oc2ccnc(N(C(=O)Oc3ccccc3)C(=O)Oc3ccccc3)c2)cc1F
Agent: CN(C)[P+](On1nnc2ccccc21)(N(C)C)N(C)C
Agent: F[P-](F)(F)(F)(F)F
Solvent: CN(C)C=O
Solvent: CCN(CC)CC
Product: O=C(Oc1ccccc1)N(C(=O)Oc1ccccc1)c1cc(Oc2ccc(NC(=O)C3(C(=O)Nc4ccccc4)CC3)c(F)c2)ccn1
Reaction time: 8 h
Yield: 87.9 %

Procedure:
A crude product of [4-(4-amino-3-fluorophenoxy)pyridin-2-yl]-N-(phenoxycarbonyl)carbamic acid phenyl ester (219 mg) was dissolved in N,N-dimethylformamide (5 ml). 1-(Phenylcarbamoyl)cyclopropanecarboxylic acid (196 mg), triethylamine (0.133 ml) and benzotriazol-1-yloxytris(dimethylamino)phosphonium hexafluorophosphate (422 mg) were added under a nitrogen atmosphere at room temperature, followed by stirring overnight. Liquid-liquid separation was carried out after addition of ethyl acetate and water to the reaction mixture. The organic layer was washed with a saturated aqueous solution of sodium hydrogencarbonate (3 times) and brine in this order, and dried over anhydrous sodium sulfate. The solvent was removed and the resultant residue was purified by silica gel column chromatography (eluent; heptane:ethyl acetate=3:2) to provide the titled compound as white powder (271 mg).
Reaction SMILES: [NH2:1][C:2]1[N:11]=[C:10](N)[C:9]2[C:4](=[C:5]3[CH:20]=[CH:19][CH:18]=[CH:17][C:6]3=[C:7]3[CH:16]=[CH:15][CH:14]=[CH:13][C:8]3=2)[N:3]=1.[NH4+].[OH-:22]>Cl>[NH2:1][C:2]1[NH:11][C:10](=[O:22])[C:9]2[C:4](=[C:5]3[CH:20]=[CH:19][CH:18]=[CH:17][C:6]3=[C:7]3[CH:16]=[CH:15][CH:14]=[CH:13][C:8]3=2)[N:3]=1
Reactant: [OH-]
Reactant: Nc1nc(N)c2c3ccccc3c3ccccc3c2n1
Agent: Cl
Agent: [NH4+]
Product: Nc1nc2c3ccccc3c3ccccc3c2c(=O)[nH]1
Reaction time: 0.33 h

Procedure:
A suspension of 2,4-diaminodibenzo[f,h]quinazoline (0.20 g, 0.76 mmol) in 1 N HCl (150 ml) was stirred at reflux for 24 h, then neutralized with NH4OH. The resulting solid was filtered, washed with water and methanol, then suspended in warm methanol (50 ml) for 20 minutes, filtered and dried at 90° C under reduced pressure. The solid was nearly dissolved in ethanol (100 ml) and 1 N NaOH (˜1.5 ml), filtered, and the filtrate neutralized with acetic acid to give a precipitate which was filtered, washed with ethanol, and dried at 90° C. under reduced pressure. The solid was briefly heated to reflux in pivalic anhydride (4 ml), the solution concentrated in vacuo, and the residue subjected to chromatography on silica gel, eluting with methylene chloride containing a small precentage of ethyl acetate. The pivalamide (not characterized) was hydrolyzed in a solution of methanol (9 ml) and 1 N NaOH (1 ml) at reflux for 1.5 hours. The solution was neutralized with acetic acid, and the precipitate filtered, washed with methanol and dried at 90° C. under reduced pressure to give 2-aminodibenzo[f,h]quinazolin-4-(3H)-one as a beige solid (0.10 g). 1H NMR (DMSO-d6, 200 MHz) δ: 6.69 (br s, 2H, NH2), 7.47-7.84 (m, 4H, Ar), 8.66-8.80 (m, 2H, Ar), 8.96 (dd, J=8, 1 Hz, 1H, Ar), 9.75-9.83 (m, 1H, Ar), 11.26 (br 5, 1H, NH). Mass spectrum (CI—CH4) 262 (M+1, 100%). Anal. Calculated for C16H11N3O: C, 73.55; H, 4.24; N, 16.08. Found: C, 73.52; H, 4.27; N, 16.03.
Reaction SMILES: [C:1]([C:3]1[CH:4]=[C:5]2[C:13](=[CH:14][CH:15]=1)[N:12]([CH2:16][C:17]1[CH:22]=[CH:21][CH:20]=[C:19]([F:23])[CH:18]=1)[C:11]1[CH2:10][CH2:9][C@@H:8]([NH:24][C:25](=[O:29])[CH:26]([CH3:28])[CH3:27])[CH2:7][C:6]2=1)#N.C(O)=[O:31]>O.CO>[F:23][C:19]1[CH:18]=[C:17]([CH:22]=[CH:21][CH:20]=1)[CH2:16][N:12]1[C:11]2[CH2:10][CH2:9][C@@H:8]([NH:24][C:25](=[O:29])[CH:26]([CH3:27])[CH3:28])[CH2:7][C:6]=2[C:5]2[C:13]1=[CH:14][CH:15]=[C:3]([CH:1]=[O:31])[CH:4]=2
Reactant: O=CO
Reactant: CC(C)C(=O)N[C@@H]1CCc2c(c3cc(C#N)ccc3n2Cc2cccc(F)c2)C1
Solvent: O
Solvent: CO
Product: CC(C)C(=O)N[C@@H]1CCc2c(c3cc(C=O)ccc3n2Cc2cccc(F)c2)C1
Temperature: 90 °C
Yield: 89 %

Procedure:
Add Al—Ni catalyst [12635-27-7] (3.0 g) to a solution of (R)-N-(6cyano9-(3-fluorobenzyl)-2,3,4,9-tetrahydro-1H-carbazol-3-yl)isobutyramide (Example 123) (2.50 g, 6.42 mmol) in formic acid (96%, 40 mL) and water (5 mL). Heat the reaction mixture to 90° C. for 18 h, then add 2 g fresh Al—Ni catalyst. Heat to reflux for 18 h, cool to 60° C., dilute with MeOH (30 mL), and resume heating. When reflux has begun, filter the reaction mixture while hot through filter paper. Concentrate the filtrate in-vacuo. Dilute the residue with water (30 mL) and saturated aqueous NaHCO3 (30 mL), then extract into EtOAc (3×150 mL). Dry the organics (MgSO4), filter, and concentrate to give 2.25g (89%) of the title compound as a brown solid. MS (ES): m/z 393 (M+1); HPLC (Method B): Rt=4.57 min (91%).
Reaction SMILES: [Cl:1][C:2]1[N:9]=[C:8](Cl)[C:7]([Cl:11])=[C:6]([CH3:12])[C:3]=1[C:4]#[N:5].[CH3:13][S-:14].[Na+]>CO>[Cl:1][C:2]1[N:9]=[C:8]([S:14][CH3:13])[C:7]([Cl:11])=[C:6]([CH3:12])[C:3]=1[C:4]#[N:5]
Reactant: C[S-]
Reactant: Cc1c(Cl)c(Cl)nc(Cl)c1C#N
Agent: [Na+]
Solvent: CO
Product: CSc1nc(Cl)c(C#N)c(C)c1Cl
Temperature: 0 °C
Reaction time: 1 h
Yield: 99.6 %

Procedure:
To a slurry of 2,5,6-trichloro-4-methyl-nicotinonitrile (10.0 g, 45.2 mmol, Tetrahedron, 1977, 33, 113-117) in MeOH (150 ml) at 0° C. is added solid sodium thiomethoxide (3.33 g, 45.2 mmol). The mixture is stirred at 0° C. for 1 hour, then room temperature for 1 hour. The reaction is quenched by the addition of water (250 ml). The mixture is partitioned between water and EtOAc (500 ml each), and the layers are shaken and separated. The organic layer is dried (anhydrous magnesium sulfate), filtered, and concentrated to give the title compound as a yellow solid (10.5 g, 99%). Mass (m/z): 233.0 (M++1).
Reaction SMILES: [F:1][C:2]1[CH:3]=[N:4][C:5]([C@@H:8]([NH2:10])[CH3:9])=[N:6][CH:7]=1.Cl[C:12]1[N:17]=[C:16]([NH:18][C:19]2[CH:23]=[C:22]([CH3:24])[NH:21][N:20]=2)[C:15]([CH3:25])=[CH:14][N:13]=1.CCN(C(C)C)C(C)C>CCCCO>[F:1][C:2]1[CH:3]=[N:4][C:5]([C@@H:8]([NH:10][C:12]2[N:17]=[C:16]([NH:18][C:19]3[CH:23]=[C:22]([CH3:24])[NH:21][N:20]=3)[C:15]([CH3:25])=[CH:14][N:13]=2)[CH3:9])=[N:6][CH:7]=1
Reactant: C[C@H](N)c1ncc(F)cn1
Reactant: Cc1cc(Nc2nc(Cl)ncc2C)n[nH]1
Solvent: CCCCO
Solvent: CCN(C(C)C)C(C)C
Product: Cc1cc(Nc2nc(N[C@@H](C)c3ncc(F)cn3)ncc2C)n[nH]1
Temperature: 180 °C
Yield: 36.3 %

Procedure:
A microwave reaction vessel was charged with (S)-1-(5-fluoropyrimidin-2-yl)ethanamine (Method 7, 111 mg, 0.63 mmol), 2-chloro-5-methyl-N-(5-methyl-1H-pyrazol-3-yl)pyrimidin-4-amine (Method 22, 0.50 g, 1.77 mmol), and DIPEA (0.225 mL, 1.26 mmol). Anhydrous n-BuOH (2.1 ml) was added, and the tube was sealed and heated in a microwave reactor at 180° C. for 4 hours. The solvent was removed under reduced pressure and the residue was purified by Gilson (5-95% MeCN/H2O, 15 minutes) to give the titled compound as solid (75 mg) 1H NMR (300 MHz, DMSO-d6) δ 10.08 (s, 1H) 8.93 (s, 2H) 8.70 (s, 1H) 7.74 (s, 1H) 5.98 (s, 1H) 4.79-5.44 (m, 1H) 2.23 (s, 3H) 2.10 (s, 3H) 1.57 (d, 3H); m/z 330.
Reaction SMILES: [CH3:1][C:2]([C:18]1[CH:26]=[CH:25][CH:24]=[CH:23][C:19]=1[C:20](O)=[O:21])([CH3:17])[CH2:3][C:4]([C:13]([F:16])([F:15])[F:14])([O:8][Si:9]([CH3:12])([CH3:11])[CH3:10])[CH2:5][C:6]#[CH:7].[N:27]1C=CC=CC=1.S(Cl)(Cl)=O>ClCCl>[CH3:1][C:2]([C:18]1[CH:26]=[CH:25][CH:24]=[CH:23][C:19]=1[C:20]([NH2:27])=[O:21])([CH3:17])[CH2:3][C:4]([C:13]([F:16])([F:15])[F:14])([O:8][Si:9]([CH3:12])([CH3:11])[CH3:10])[CH2:5][C:6]#[CH:7]
Reactant: c1ccncc1
Reactant: C#CCC(CC(C)(C)c1ccccc1C(=O)O)(O[Si](C)(C)C)C(F)(F)F
Solvent: O=S(Cl)Cl
Solvent: ClCCl
Product: C#CCC(CC(C)(C)c1ccccc1C(N)=O)(O[Si](C)(C)C)C(F)(F)F
Reaction time: 0.25 h
Yield: 43.8 %

Procedure:
To a solution of 2-(1,1-dimethyl-3-trifluoromethyl-3-trimethylsilanyloxyhex-5-ynyl)benzoic acid (246 mg, 0.64 mmol) in 5 mL of dichloromethane was added pyridine (77 μL, 0.96 mmol) followed by thionyl chloride (56 μL, 0.76 mmol). The reaction was stirred for 15 minutes then the volatiles were removed in vacuo. The crude acid chloride was treated with 7 M ammonia in 5.0 mL of MeOH. The mixture was stirred for 15 minutes then diluted with 75 mL of EtOAc, washed with two 25 mL portions of saturated aqueous sodium bicarbonate solution, dried over magnesium sulfate, filtered, and concentrated in vacuo. Purification of the crude by flash chromatography (12 g SiO2, hexanes to 1:1 hexanes:EtOAc) gave 2-(1,1-dimethyl-3-trifluoromethyl-3-trimethylsilanyloxyhex-5-ynyl)benzamide as a pale yellow solid (108 mg, 44%). MS (ES+) m/z 386 [M+H]+.
Reaction SMILES: [Cl:1][C:2]1[CH:9]=[CH:8][CH:7]=[C:6]([F:10])[C:3]=1[C:4]#[N:5].S(=O)(=O)(O)[OH:12]>>[Cl:1][C:2]1[CH:9]=[CH:8][CH:7]=[C:6]([F:10])[C:3]=1[C:4]([NH2:5])=[O:12]
Reactant: N#Cc1c(F)cccc1Cl
Reactant: O=S(=O)(O)O
Product: NC(=O)c1c(F)cccc1Cl

Procedure:
A solution of 2-chloro-6-fluorobenzonitrile (8.0 g, 51.61 mmol) in conc. sulphuric acid (50 mL) was heated at 60-70° C. for 6-7 h. The reaction mass was quenched in water and extracted with DCM. The organic layer was dried over anhydrous sodium sulphate and concentrated to afford 5.5 g of desired product.
Reaction SMILES: [Br:1][C:2]1[CH:3]=[CH:4][C:5]2[N:6]([N:9]=[C:10]([NH2:12])[N:11]=2)[C:7]=1Cl.[CH:13]1([NH2:19])[CH2:18][CH2:17][CH2:16][CH2:15][CH2:14]1>>[Br:1][C:2]1[CH:3]=[CH:4][C:5]2[N:6]([N:9]=[C:10]([NH2:12])[N:11]=2)[C:7]=1[NH:19][CH:13]1[CH2:18][CH2:17][CH2:16][CH2:15][CH2:14]1
Reactant: NC1CCCCC1
Reactant: Nc1nc2ccc(Br)c(Cl)n2n1
Product: Nc1nc2ccc(Br)c(NC3CCCCC3)n2n1

Procedure:
The title compound was prepared following procedure described for intermediate A9 but starting from 6-bromo-5-chloro[1,2,4]triazolo[1,5-a]pyridin-2-amine (3.0 g; 12.1 mmol; 1.0 eq.) and cyclohexylamine (12.0 mL; 104.9 mmol; 8.65 eq.) to give the title compound as a dark foam (2.5 g, 66%). HPLC, Rt: 3.21 min. (purity 76.6%). LC/MS, M+(ESI): 310.0.
Reaction SMILES: [O:1]1[C:5]2=[CH:6][C:7]3[CH:8]=[C:9]([C:13]([O:15]CC)=[O:14])[NH:10][C:11]=3[CH:12]=[C:4]2[O:3][CH2:2]1.O[Li].O>C(O)C>[O:1]1[C:5]2=[CH:6][C:7]3[CH:8]=[C:9]([C:13]([OH:15])=[O:14])[NH:10][C:11]=3[CH:12]=[C:4]2[O:3][CH2:2]1
Reactant: CCOC(=O)c1cc2cc3c(cc2[nH]1)OCO3
Agent: [Li]O
Solvent: O
Solvent: CCO
Product: O=C(O)c1cc2cc3c(cc2[nH]1)OCO3
Yield: 85.2 %

Procedure:
To a solution of ethyl 5H-[1,3]dioxolo[4,5-f]indole-6-carboxylate (I-4b: 0.4 g, 1.716 mmol) in ethanol (8 mL) was added LiOH.H2O (0.144 g, 3.433 mmol) and refluxed for 16 h. The solvent was evaporated under reduced pressure and the residue was dissolved in water (10 mL). The aqueous layer was acidified with 10% aq. HCl solution to pH 6.0, precipitated solid was filtered, residue was washed with water and dried under vacuum to afford 0.3 g (86%) of 5H-[1,3]dioxolo[4,5-f]indole-6-carboxylic acid (I-4c) as an off-white solid.
Reaction SMILES: [CH3:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[O:9][C:10]([CH3:22])=[C:11]([CH2:13][O:14][CH:15]3[CH2:20][CH2:19][CH2:18][CH:17]([OH:21])[CH2:16]3)[N:12]=2)=[CH:4][CH:3]=1>C(OC=C)(=O)C>[CH3:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[O:9][C:10]([CH3:22])=[C:11]([CH2:13][O:14][C@@H:15]3[CH2:20][CH2:19][CH2:18][C@H:17]([OH:21])[CH2:16]3)[N:12]=2)=[CH:4][CH:3]=1
Reactant: Cc1ccc(-c2nc(COC3CCCC(O)C3)c(C)o2)cc1
Solvent: C=COC(C)=O
Product: Cc1ccc(-c2nc(CO[C@@H]3CCC[C@H](O)C3)c(C)o2)cc1
Reaction time: 0.5 h
Yield: 52.8 %

Procedure:
16.3 g of the racemic 3-[2-(4-methylphenyl)-5-methyloxazol-4-yl-methoxy]cyclohexan-1-ol were dissolved in 100 ml of vinyl acetate, admixed with 1.9 g of Chirazyme L-2, lyo., and stirred at 20–23° C. After about 30 minutes, the enzyme was filtered off and the solution concentrated under reduced pressure, crude product: 16.6 g. After chromatography on silica gel (10:1–0:1 n-heptane/ethyl acetate), 8.6 g of (1S,3R)-3-[2-(4-methylphenyl)-5-methyloxazol-4-ylmethoxy]cyclohexan-1-ol and 6.8 g of the (1R,3S)-acetate are obtained.
Reaction SMILES: [NH2:1][C:2]1[CH:18]=[C:17]([N+:19]([O-:21])=[O:20])[CH:16]=[CH:15][C:3]=1[C:4]([NH:6][C:7]1[CH:12]=[CH:11][C:10]([O:13][CH3:14])=[CH:9][CH:8]=1)=[O:5].N1C=CC=CC=1.[C:28]([C:32]1[CH:40]=[CH:39][C:35]([C:36](Cl)=[O:37])=[CH:34][CH:33]=1)([CH3:31])([CH3:30])[CH3:29]>C(Cl)Cl>[C:28]([C:32]1[CH:33]=[CH:34][C:35]([C:36]([NH:1][C:2]2[CH:18]=[C:17]([N+:19]([O-:21])=[O:20])[CH:16]=[CH:15][C:3]=2[C:4]([NH:6][C:7]2[CH:12]=[CH:11][C:10]([O:13][CH3:14])=[CH:9][CH:8]=2)=[O:5])=[O:37])=[CH:39][CH:40]=1)([CH3:31])([CH3:29])[CH3:30]
Reactant: CC(C)(C)c1ccc(C(=O)Cl)cc1
Reactant: COc1ccc(NC(=O)c2ccc([N+](=O)[O-])cc2N)cc1
Solvent: ClCCl
Solvent: c1ccncc1
Product: COc1ccc(NC(=O)c2ccc([N+](=O)[O-])cc2NC(=O)c2ccc(C(C)(C)C)cc2)cc1
Reaction time: 1.5 h
Yield: 76.9 %

Procedure:
To a mixture of 2-amino-4-nitro-N-(4-methoxyphenyl)benzamide (2.0 g, 7.0 mmol) and pyridine (0.62 mL, 7.7 mmol) in methylene chloride (40 mL) was added 4-tert-butylbenzoyl chloride (1.44 mL, 7.35 mmol). After stirring for 1.5 h, silica gel (30 g) was added and the solvent evaporated with a stream of nitrogen. The resulting material was chromatographed (silica gel, 5% hexanes/95% methylene chloride to 1.25% ethyl acetate/98.75% methylene chloride) to give 2.41 g (77%) of the title compound as a yellow solid; mp 221° C.
Reaction SMILES: [N:1]1([S:11]([C:14]2[CH:22]=[CH:21][C:17]([C:18]([OH:20])=O)=[CH:16][CH:15]=2)(=[O:13])=[O:12])[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH2:4][CH2:3][CH2:2]1.[C:23]1([CH3:35])[CH:28]=[CH:27][C:26]([C:29]2[N:30]=[C:31]([NH2:34])[S:32][CH:33]=2)=[CH:25][CH:24]=1>>[N:1]1([S:11]([C:14]2[CH:22]=[CH:21][C:17]([C:18]([NH:34][C:31]3[S:32][CH:33]=[C:29]([C:26]4[CH:27]=[CH:28][C:23]([CH3:35])=[CH:24][CH:25]=4)[N:30]=3)=[O:20])=[CH:16][CH:15]=2)(=[O:13])=[O:12])[C:2]2[C:9](=[CH:10][CH:5]=[CH:4][CH:3]=2)[CH2:8][CH2:7][CH2:6]1
Reactant: O=C(O)c1ccc(S(=O)(=O)N2CCCc3ccccc32)cc1
Reactant: Cc1ccc(-c2csc(N)n2)cc1
Product: Cc1ccc(-c2csc(NC(=O)c3ccc(S(=O)(=O)N4CCCc5ccccc54)cc3)n2)cc1

Procedure:
4-(3,4-dihydroquinolin-1(2H)-ylsulfonyl)benzoic acid (1) (100 mg, 0.32 mmol) was treated with 4-p-tolylthiazol-2-amine (50 mg, 0.26 mmol) using method B. The residue was purified using flash chromatography eluting with 0-30% EtOAc in hexanes to give 4-(3,4-dihydroquinolin-1(2H)-ylsulfonyl)-N-(4-p-tolylthiazol-2-yl)benzamide as a yellow solid. Yield: 18 mg (14%). 1H-NMR: 8.21 (d, J=8.5 Hz, 2H), 7.83 (d, J=8.0 Hz, 2H), 7.75 (d, J=8.5 Hz, 2H), 7.65 (s, 1H), 7.61 (d, J=8.0 Hz, 1H), 7.27-7.19 (m, 3H), 7.14-7.08 (m, 2H), 3.84-3.80 (m, 2H), 2.45 (t, J=7.0 Hz, 2H), 1.66-1.59 (m, 2H).