Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: Cl.[Cl:2][C:3]1[CH:4]=[C:5]2[C:9](=[CH:10][CH:11]=1)[NH:8][CH:7]=[C:6]2[CH2:12][CH2:13][NH2:14].[N:15]1([C:20]2[CH:21]=[C:22]([N:26]3[CH2:30][CH2:29][CH:28]([C:31](O)=[O:32])[C:27]3=[O:34])[CH:23]=[CH:24][CH:25]=2)[CH:19]=[CH:18][CH:17]=[CH:16]1.N1(C2C=C(N3CCC(C(O)=O)C3=O)C=CC=2)C=CC=C1.C1CN([P+](ON2N=NC3C=CC=CC2=3)(N2CCCC2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F.C(N(CC)C(C)C)(C)C>CN(C=O)C>[N:15]1([C:20]2[CH:21]=[C:22]([N:26]3[CH2:30][CH2:29][CH:28]([C:31]([NH:14][CH2:13][CH2:12][C:6]4[C:5]5[C:9](=[CH:10][CH:11]=[C:3]([Cl:2])[CH:4]=5)[NH:8][CH:7]=4)=[O:32])[C:27]3=[O:34])[CH:23]=[CH:24][CH:25]=2)[CH:19]=[CH:18][CH:17]=[CH:16]1
Reactant: NCCc1c[nH]c2ccc(Cl)cc12
Reactant: O=C(O)C1CCN(c2cccc(-n3cccc3)c2)C1=O
Agent: Cl
Agent: F[P-](F)(F)(F)(F)F
Agent: c1ccc2c(c1)nnn2O[P+](N1CCCC1)(N1CCCC1)N1CCCC1
Solvent: CCN(C(C)C)C(C)C
Solvent: CN(C)C=O
Product: O=C(NCCc1c[nH]c2ccc(Cl)cc12)C1CCN(c2cccc(-n3cccc3)c2)C1=O
Yield: 30 %

Procedure:
This compound was prepared according to method E with 2-(5-chloro-1H-indol-3-yl)ethanamine hydrochloride (0.100 g; 0.433 mmol), 1-(3-(1H-pyrrol-1-yl)phenyl)-2-oxopyrrolidine-3-carboxylic acid 1-(3-(1H-pyrrol-1-yl)phenyl)-2-oxopyrrolidine-3-carboxylic acid (0.117 g; 0.433 mmol), PyBOP (0.225 g; 0.433 mmol), N,N diisopropylethylamine (0.186 mL; 1.08 mmol) in DMF (3 mL). The crude mixture was purified flash chromatography on silica (eluent 20 to 100% ethyl acetate in heptane and 2 to 20% ethyl acetate in dichloromethane) to yield 0.058 g (30%) of 1-(3-(1H-pyrrol-1-yl)phenyl)-N-(2-(5-chloro-1H-indol-3-yl)ethyl)-2-oxopyrrolidine-3-carboxamide as a white solid.
Reaction SMILES: [CH2:1]([OH:12])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][OH:11].[OH-].[K+].[CH2:15]([CH:17]([CH2:20][CH2:21][CH2:22][CH3:23])[CH2:18]Br)[CH3:16]>C1(C)C(C)=CC=CC=1>[CH2:15]([CH:17]([CH2:20][CH2:21][CH2:22][CH3:23])[CH2:18][O:12][CH2:1][CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][OH:11])[CH3:16]
Reactant: OCCCCCCCCCCO
Reactant: CCCCC(CC)CBr
Agent: [K+]
Agent: [OH-]
Solvent: Cc1ccccc1C
Product: CCCCC(CC)COCCCCCCCCCCO
Temperature: 25 °C
Reaction time: 15 h
Yield: 72.1 %

Procedure:
A 1-liter flask equipped with a stirrer and distiller was charged with 25 g (0.14 mol) of 1,10-decanediol, 8.09 g (0.14 mol) of KOH and 300 ml of xylene, and the resultant mixture was heated at 120° C. for 1 hour, thereby distilling off water formed. To this reaction mixture, were added 23.1 g (0.12 mol) of 2-ethylhexyl bromide, and the resulting mixture was heated and stirred for 15 hours. After completion of the reaction, the reaction mixture was cooled to room temperature and washed with water. After the solvent was distilled off under reduced pressure, the resulting residue was purified by column chromatography on silica gel, thereby obtaining 24.8 g (yield: 72%) of 10-(2-ethylhexyloxy)decanol.
Reaction SMILES: C(N(CC)CC)C.C(O)=O.[Br:11][C:12]1[CH:20]=[CH:19][C:18]([F:21])=[C:17]2[C:13]=1[CH2:14][CH2:15][C:16]2=[O:22].O>ClCCl>[Br:11][C:12]1[CH:20]=[CH:19][C:18]([F:21])=[C:17]2[C:13]=1[CH2:14][CH2:15][C@@H:16]2[OH:22]
Reactant: O=C1CCc2c(Br)ccc(F)c21
Solvent: ClCCl
Solvent: O
Solvent: CCN(CC)CC
Product: O[C@H]1CCc2c(Br)ccc(F)c21
Temperature: 0 °C
Reaction time: 8 h
Yield: 94.5 %

Procedure:
Triethylamine (26.2 mL, 187 mmol) is dissolved in dichloromethane (100 mL) and cooled to 0° C. then formic acid (7.96 mL, 211 mmol) is added dropwise with cooling. 4-Bromo-7-fluoro-indan-1-one (European patent EP2042480, 13.8 g, 60 mmol) is added and the mixture degassed with a flow of argon. Chloro([1S,2S)-(+2-amino-1,2-diphenylethyl](4-toluenesulfonyl)amido)(mesitylene)ruthenium(II) complex (375 mg, 0.6 mmol) is added and the mixture is stirred overnight at room temperature. Water is added, the mixture shaken and the phases separated. The organic phase is dried and concentrated under vacuum. The residue is purified by flash chromatography (0-20% ethyl acetate in cyclohexane) to give the title compound (Yield 13.1 g). GC (METHOD 1): tR=9.35 min; Mass spectrum (EI+): m/z=229, 231 [M]+, e.e. 100% by chiral HPLC (Column: Daicel Chiralcel OJ-H, 4.6×250 mm, 5 μm Mobile phase: hexane:ethanol 95:5, 1 mL/min, 25° C.) tR=9.87 min.
Reaction SMILES: [Br:1][C:2]1[CH:9]=[CH:8][C:7]([O:10][CH3:11])=[CH:6][C:3]=1[CH:4]=[O:5].[CH:12](O)([OH:14])[CH3:13]>C1(C)C=CC=CC=1.CC1C=CC(S(O)(=O)=O)=CC=1>[Br:1][C:2]1[CH:9]=[CH:8][C:7]([O:10][CH3:11])=[CH:6][C:3]=1[CH:4]1[O:14][CH2:12][CH2:13][O:5]1
Reactant: CC(O)O
Reactant: COc1ccc(Br)c(C=O)c1
Agent: Cc1ccc(S(=O)(=O)O)cc1
Solvent: Cc1ccccc1
Product: COc1ccc(Br)c(C2OCCO2)c1
Temperature: 25 °C
Yield: 98.5 %

Procedure:
To a solution of 2-bromo-5-methoxybenzaldehyde (5.0 g, 23.2 mmol) in toluene (300 mL) was added ethanediol (2.16 g, 34.2 mmol) and p-TsOH (20 mg), whereafter the mixture was refluxed for 12 hours. The resulting mixture was cooled to room temperature, washed with NaHCO3/aq, dried (Na2SO4), and concentrated to yield 5.918 g (98%) of the sub-title compound.
Reaction SMILES: [BH4-].[Na+].[CH2:3]([O:5][C:6]([C:8]1[S:9][C:10](S(C)(=O)=O)=[C:11]([C:27]#[N:28])[C:12]=1[C:13]1[CH:18]=[CH:17][C:16]([C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][C:20]=2[C:25]#[N:26])=[CH:15][CH:14]=1)=[O:7])[CH3:4]>CCO>[CH2:3]([O:5][C:6]([C:8]1[S:9][CH:10]=[C:11]([C:27]#[N:28])[C:12]=1[C:13]1[CH:14]=[CH:15][C:16]([C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][C:20]=2[C:25]#[N:26])=[CH:17][CH:18]=1)=[O:7])[CH3:4]
Reactant: CCOC(=O)c1sc(S(C)(=O)=O)c(C#N)c1-c1ccc(-c2ccccc2C#N)cc1
Agent: [BH4-]
Agent: [Na+]
Solvent: CCO
Product: CCOC(=O)c1scc(C#N)c1-c1ccc(-c2ccccc2C#N)cc1
Temperature: 25 °C
Yield: 55.8 %

Procedure:
Add NaBH4 (10 mg, 0.26 mmol) to a solution of 4-cyano-3-(2′-cyano-biphenyl-4-yl)-5-methanesulfonyl-thiophene-2-carboxylic acid ethyl ester (95 mg, 0.22 mmol) in 2 mL of EtOH at 0° C. Remove the ice-bath and stir at room temperature. After 30 minutes add another 10 mg of NaBH4 and stir an additional 30 minutes. Remove the solvents in vacuo and extract the residue with 50 mL of 1/9 MeOHJ CH2Cl2. Evaporate and chromatograph over silica gel (100/0 to 90/10 toluene/EtOAc) to give 44 mg (56%) of the title compound as a white solid. HPLC=94%.
Reaction SMILES: [F:1][C:2]1[CH:14]=[CH:13][C:5]2[S:6][CH:7]=[C:8]([CH2:9][CH:10]([CH3:12])[CH3:11])[C:4]=2[CH:3]=1.[Cl:15][S:16](O)(=[O:18])=[O:17]>C(Cl)(Cl)Cl>[F:1][C:2]1[CH:14]=[CH:13][C:5]2[S:6][C:7]([S:16]([Cl:15])(=[O:18])=[O:17])=[C:8]([CH2:9][CH:10]([CH3:11])[CH3:12])[C:4]=2[CH:3]=1
Reactant: O=S(=O)(O)Cl
Reactant: CC(C)Cc1csc2ccc(F)cc12
Solvent: ClC(Cl)Cl
Product: CC(C)Cc1c(S(=O)(=O)Cl)sc2ccc(F)cc12
Temperature: 25 °C
Reaction time: 3 h
Yield: 60.5 %

Procedure:
To a solution of 5-fluoro-3-isobutyl-benzo[b]thiophene 0.55 g) in chloroform (10 ml) was added chlorosulfonic acid (1.54 g), and the resulting mixture was stirred at rt for 3 h, quenched with ice/water, and extracted with methylene chloride. The organic phases were washed with water and aqueous sodium bicarbonate solution, dried and concentrated. The residue was chromatographed on silica gel using heptane/ethyl acetate as eluent to obtain the title compound (0.49 g) as a colorless oil. MS (EI): 306.8 (M)
Reaction SMILES: N1C=CC=CC=1.[Cl:7][C:8]1[CH:9]=[C:10]2[C:14](=[CH:15][CH:16]=1)[NH:13][C:12](=[O:17])[C:11]2([C:19]1[C:20]([O:25][CH2:26][CH3:27])=[N:21][CH:22]=[CH:23][CH:24]=1)O.S(Cl)([Cl:30])=O>ClCCl>[Cl:30][C:11]1([C:19]2[C:20]([O:25][CH2:26][CH3:27])=[N:21][CH:22]=[CH:23][CH:24]=2)[C:10]2[C:14](=[CH:15][CH:16]=[C:8]([Cl:7])[CH:9]=2)[NH:13][C:12]1=[O:17]
Reactant: O=S(Cl)Cl
Reactant: CCOc1ncccc1C1(O)C(=O)Nc2ccc(Cl)cc21
Solvent: ClCCl
Solvent: c1ccncc1
Product: CCOc1ncccc1C1(Cl)C(=O)Nc2ccc(Cl)cc21
Temperature: 0 °C
Reaction time: 1 h
Yield: 110.7 %

Procedure:
4.4 ml (54.3 mmol) of pyridine were added to a suspension of 13.3 g (43.6 mmol) of 5-chloro-3-(2-ethoxypyridin-3-yl)-3-hydroxy-1,3-dihydroindol-2-one from example a.1 in 50 ml of dichloromethane. After the reaction mixture had been cooled to 0° C., 3.8 ml (52.3 mmol) of thionyl chloride was added dropwise. The mixture was stirred at room temperature for one hour and then poured into ice-water. After stirring for 15 minutes, the organic phase was separated off. The aqueous phase was extracted several times with dichloromethane. The combined organic phase was dried over magnesium sulfate and filtered, and the solvent was removed in vacuo. 15.6 g of the title compound were obtained as a yellowish solid which was employed without further purification in the next stage.
Reaction SMILES: [N:1]1([CH2:10]/[C:11](=[N:22]\[NH:23][S:24](C2C=CC(C)=CC=2)(=O)=O)/[C:12]2[C:21]3[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=3)[CH:15]=[CH:14][CH:13]=2)[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[N:2]1.O=S(Cl)Cl>>[N:1]1([C:10]2[S:24][N:23]=[N:22][C:11]=2[C:12]2[C:21]3[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=3)[CH:15]=[CH:14][CH:13]=2)[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[N:2]1
Reactant: Cc1ccc(S(=O)(=O)N/N=C(\Cn2nnc3ccccc32)c2cccc3ccccc23)cc1
Solvent: O=S(Cl)Cl
Product: c1ccc2c(-c3nnsc3-n3nnc4ccccc43)cccc2c1
Temperature: 60 °C
Reaction time: 18 h

Procedure:
A mixture of (Z)—N′-(2-(1H-benzo[d][1,2,3]triazol-1-yl)-1-(naphthalen-1-yl)ethylidene)-4-methylbenzenesulfonohydrazide (1 g, 2.19 mmol) and SOCl2 (25 mL) was stirred at 60° C. for 18 h and then concentrated and purified by TLC (100% DCM) to afford 5-(1H-benzo[d][1,2,3]triazol-1-yl)-4-(naphthalen-1-yl)-1,2,3-thiadiazole as an amber solid.
Reaction SMILES: [OH-].[K+].[C:3]([N:6](C)[C@H:7]1[C@@H:12]([OH:13])[CH2:11][C@H:10]2[C@H:14]3[C@H:24]([CH2:25][CH2:26][C@:8]12[CH3:9])[C@:22]1([CH3:23])[C@H:17]([CH2:18][C@@H:19]([OH:27])[CH2:20][CH2:21]1)[CH2:16][CH2:15]3)(=O)C>C(O)C>[CH3:3][NH:6][C@H:7]1[C@@H:12]([OH:13])[CH2:11][C@H:10]2[C@H:14]3[C@H:24]([CH2:25][CH2:26][C@:8]12[CH3:9])[C@:22]1([CH3:23])[C@H:17]([CH2:18][C@@H:19]([OH:27])[CH2:20][CH2:21]1)[CH2:16][CH2:15]3
Reactant: CC(=O)N(C)[C@H]1[C@@H](O)C[C@H]2[C@@H]3CC[C@H]4C[C@@H](O)CC[C@]4(C)[C@H]3CC[C@]12C
Agent: [K+]
Agent: [OH-]
Solvent: CCO
Product: CN[C@H]1[C@@H](O)C[C@H]2[C@@H]3CC[C@H]4C[C@@H](O)CC[C@]4(C)[C@H]3CC[C@@]21C
Yield: 82.5 %

Procedure:
Potassium hydroxide (4.8 ml; 10 N) was added to a stirred suspension of 17β-(N-acetyl-methylamino)-5α-androstane-3β,16β-diol (4.8 g) in ethanol (96 ml) and the stirred mixture was heated under reflux for 2 h. A clear solution was obtained after 5 min., and a solid product precipitated after 30 min. The mixture was cooled, water was added, followed by brine and the product was filtered off and washed with water. Crystallisation from aqueous ethanol gave 17β-methylamino-5α-androstane-3β,16β-diol as prisms (3.5 g), m.p. 241°-253° C.
Reaction SMILES: [Cl-].COC[P+](F)(F)F.C([N-]C(C)C)(C)C.[Li+].[CH2:17]1[CH2:21][O:20][CH2:19][CH2:18]1.[Si:22]([O:29][CH2:30][C:31]1[CH:32]=[C:33]2[C:38](=[CH:39][CH:40]=1)[CH:37]=[C:36](CCC=O)[CH:35]=[CH:34]2)([C:25]([CH3:28])([CH3:27])[CH3:26])([CH3:24])[CH3:23]>C1COCC1>[C:25]([Si:22]([O:29][C:30]1[CH:37]=[CH:36][C:35]2[C:40](=[CH:39][CH:38]=[C:33]([CH2:32][CH2:18][CH:17]=[CH:21][O:20][CH3:19])[CH:34]=2)[CH:31]=1)([CH3:23])[CH3:24])([CH3:27])([CH3:26])[CH3:28]
Reactant: CC(C)(C)[Si](C)(C)OCc1ccc2cc(CCC=O)ccc2c1
Reactant: C1CCOC1
Agent: CC(C)[N-]C(C)C
Agent: COC[P+](F)(F)F
Agent: [Cl-]
Product: COC=CCCc1ccc2cc(O[Si](C)(C)C(C)(C)C)ccc2c1
Temperature: 25 °C
Reaction time: 1 h

Procedure:
Methoxymethyltrifluorophosphonium chloride (425 mg) was dissolved in anhydrous THF (10 ml). Then, the solution obtained was added with a 2 mol/l lithium diisopropylamide/THF solution (0.619 ml) under ice-cooling, followed by stirring at room temperature for 1 hour. A solution of the compound (296 mg) obtained in Example 121-7 in anhydrous THF was added in this solution, and the whole was stirred overnight at room temperature. After completion of the reaction, distilled water was added to the solution, and the whole was stirred. The solution was extracted with chloroform and the extract was washed with saturated saline solution. The organic layer was dried with anhydrous sodium sulfate. The solvent was distilled off and the residue was then purified through silica gel column chromatography (hexane/ethyl acetate), thereby obtaining the subject compound (264 mg) (geometrical-isomer mixture) as a yellow oily substance.
Reaction SMILES: Cl[CH2:2][CH2:3][CH2:4][CH2:5][S:6][C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1.[CH3:13][CH:14]([CH3:30])[C:15]([NH:17][C:18]1[CH:23]=[CH:22][CH:21]=[C:20]([CH:24]2[CH2:29][CH2:28][NH:27][CH2:26][CH2:25]2)[CH:19]=1)=[O:16]>>[CH3:13][CH:14]([CH3:30])[C:15]([NH:17][C:18]1[CH:23]=[CH:22][CH:21]=[C:20]([CH:24]2[CH2:29][CH2:28][N:27]([CH2:2][CH2:3][CH2:4][CH2:5][S:6][C:7]3[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=3)[CH2:26][CH2:25]2)[CH:19]=1)=[O:16]
Reactant: CC(C)C(=O)Nc1cccc(C2CCNCC2)c1
Reactant: ClCCCCSc1ccccc1
Product: CC(C)C(=O)Nc1cccc(C2CCN(CCCCSc3ccccc3)CC2)c1

Procedure:
Prepared by Procedure G and Scheme B1 using [(4-chlorobutyl)sulfanyl]benzene and 2-methyl-N-[3-(4-piperidinyl)phenyl]propanamide: ESMS m/e: 410.6 (M+H)+.
Reaction SMILES: [C:1](=[N:14][OH:15])([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[OH-].[Na+].[CH:18]1([N:24]=[C:25]=[N:26][CH:27]2[CH2:32][CH2:31][CH2:30][CH2:29][CH2:28]2)[CH2:23][CH2:22][CH2:21][CH2:20][CH2:19]1>C1COCC1>[CH:27]1([NH:26][C:25](=[N:24][CH:18]2[CH2:23][CH2:22][CH2:21][CH2:20][CH2:19]2)[O:15][N:14]=[C:1]([C:8]2[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=2)[C:2]2[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=2)[CH2:28][CH2:29][CH2:30][CH2:31][CH2:32]1
Reactant: ON=C(c1ccccc1)c1ccccc1
Reactant: C(=NC1CCCCC1)=NC1CCCCC1
Agent: [Na+]
Agent: [OH-]
Solvent: C1CCOC1
Product: c1ccc(C(=NOC(=NC2CCCCC2)NC2CCCCC2)c2ccccc2)cc1
Temperature: 25 °C
Reaction time: 22 h
Yield: 36.3 %

Procedure:
To a solution of benzophenone oxime (3.94 g, 0.02 mol) in dry THF (40 ml) is added finely powdered NaOH (0.08 g) and dicyclohexylcarbodiimide (4.25 g, 0.0206 mol). The mixture is then stirred 22 h at room temperature under argon. The turbid mixture is thereafter filtered and evaporated under reduced pressure. The residue is crystallized from acetonitrile and again from acetonitrile-dichloromethane-hexane to afford 2.93 g of the title compound as a colorless solid, mp. 104-107° C.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]([C:58]2[CH:63]=[CH:62][C:61]([O:64][CH3:65])=[CH:60][CH:59]=2)([C:52]2[CH:57]=[CH:56][CH:55]=[CH:54][CH:53]=2)[O:10][CH2:11][CH2:12][CH:13]([OH:51])[CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][O:23][C@H:24]2[CH2:48][CH2:47][C@@:46]3([CH3:49])[C:26](=[CH:27][CH2:28][C@@H:29]4[C@@H:45]3[CH2:44][CH2:43][C@@:42]3([CH3:50])[C@H:30]4[CH2:31][CH2:32][C@@H:33]3[C@H:34]([CH3:41])[CH2:35][CH2:36][CH2:37][CH:38]([CH3:40])[CH3:39])[CH2:25]2)=[CH:5][CH:4]=1.[C:66]1(=[O:72])[O:71][C:69](=[O:70])[CH2:68][CH2:67]1.CCOC(C)=O>C(Cl)Cl>[CH3:65][O:64][C:61]1[CH:60]=[CH:59][C:58]([C:9]([C:6]2[CH:7]=[CH:8][C:3]([O:2][CH3:1])=[CH:4][CH:5]=2)([C:52]2[CH:53]=[CH:54][CH:55]=[CH:56][CH:57]=2)[O:10][CH2:11][CH2:12][CH:13]([O:51][C:66](=[O:72])[CH2:67][CH2:68][C:69]([OH:71])=[O:70])[CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][O:23][C@H:24]2[CH2:48][CH2:47][C@@:46]3([CH3:49])[C:26](=[CH:27][CH2:28][C@@H:29]4[C@@H:45]3[CH2:44][CH2:43][C@@:42]3([CH3:50])[C@H:30]4[CH2:31][CH2:32][C@@H:33]3[C@H:34]([CH3:41])[CH2:35][CH2:36][CH2:37][CH:38]([CH3:40])[CH3:39])[CH2:25]2)=[CH:63][CH:62]=1
Reactant: COc1ccc(C(OCCC(O)CCCCCCCCCO[C@H]2CC[C@@]3(C)C(=CC[C@H]4[C@@H]5CC[C@H]([C@H](C)CCCC(C)C)[C@@]5(C)CC[C@@H]43)C2)(c2ccccc2)c2ccc(OC)cc2)cc1
Reactant: O=C1CCC(=O)O1
Solvent: ClCCl
Solvent: CCOC(C)=O
Product: COc1ccc(C(OCCC(CCCCCCCCCO[C@H]2CC[C@@]3(C)C(=CC[C@H]4[C@@H]5CC[C@H]([C@H](C)CCCC(C)C)[C@@]5(C)CC[C@@H]43)C2)OC(=O)CCC(=O)O)(c2ccccc2)c2ccc(OC)cc2)cc1
Reaction time: 17 h

Procedure:
In a 20 mL scintillation vial was 1-((bis(4-methoxyphenyl)(phenyl)methoxy))-12-(Cholest-5-en-3β-oxy)dodecan-3-ol (0.5 g, 0.562 mmol) and succinic anhydride (0.113 g, 1.124 mmol) in DCM (10 ml) to give a colorless solution. TEA (0.313 ml, 2.249 mmol) was added and the mixture set to stir for 17 hours. The reaction was judged complete by TLC (25% EtOAc/Hex, PMA visualization). The reaction mixture was washed with 5% NaHPO4 solution (3×15 mL) and brine (1×15 mL). The organic phase was dried over sodium sulfate, filtered and concentrated to dryness for use without further purification. 1H NMR (300 MHz, CDCl3) δ0.70 (3H, s); 0.83-1.74 (49H, m); 1.77-2.12 (5H, m); 2.14-2.29 (1H, m); 2.33-2.44 (1H, m); 2.53-2.72 (4H, m); 3.00-3.09 (2H, m); 3.16 (1H, tt, J=11.2, 4.4 Hz); 3.48 (2H, t, J=6.8 Hz); 3.80 (6H, s); 4.85-5.00 (1H, m); 5.36 (1H, d, J=5.1 Hz); 6.78-6.90 (4H, m), 7.15-7.38 (7H, m); 7.40-7.49 (2H, m); 9.29 (1H, bs).
Reaction SMILES: [Li+].C[Si]([N-][Si](C)(C)C)(C)C.[NH2:11][C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1.Cl[C:19]1[CH:28]=[CH:27][C:26]2[C:21](=[C:22]([C:29]3[NH:37][C:36]4[CH:35]([CH3:38])[CH2:34][NH:33][C:32](=[O:39])[C:31]=4[CH:30]=3)[CH:23]=[CH:24][CH:25]=2)[N:20]=1.C(O)(C(F)(F)F)=O>CS(C)=O>[CH3:38][CH:35]1[CH2:34][NH:33][C:32](=[O:39])[C:31]2[CH:30]=[C:29]([C:22]3[CH:23]=[CH:24][CH:25]=[C:26]4[C:21]=3[N:20]=[C:19]([NH:11][C:12]3[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=3)[CH:28]=[CH:27]4)[NH:37][C:36]1=2
Reactant: Nc1ccccc1
Reactant: CC1CNC(=O)c2cc(-c3cccc4ccc(Cl)nc34)[nH]c21
Agent: C[Si](C)(C)[N-][Si](C)(C)C
Agent: [Li+]
Solvent: O=C(O)C(F)(F)F
Solvent: CS(C)=O
Product: CC1CNC(=O)c2cc(-c3cccc4ccc(Nc5ccccc5)nc34)[nH]c21
Reaction time: 8 h
Yield: 40.1 %

Procedure:
A solution of LHMDS (1.0 M in THF; 2.197 ml, 2.197 mmol), aniline (0.200 ml, 2.197 mmol), and 2-(2-chloroquinolin-8-yl)-7-methyl-6,7-dihydro-1H-pyrrolo[3,2-c]pyridin-4(5H)-one (Example 27; 0.137 g, 0.439 mmol) was stirred at RT for 1.5 h. An additional 2 equiv LHMDS (1.0 M in THF) was added, and the reaction was stirred overnight. The reaction was concentrated under N2, treated with DMSO and TFA (0.474 ml, 6.15 mmol), filtered, and purified by rpHPLC (Phenomenex Gemini 150×30 mm C18 column, 10-80% ACN/H2O with 0.1% TFA); product-containing fractions were treated with saturated aq. NaHCO3 and DCM. The organic layer was separated, and the aq. layer was extracted 3×DCM. The combined organic layers were then dried over Na2SO4, filtered, and concentrated in vacuo to give rac-7-methyl-2-(2-(phenylamino)quinolin-8-yl)-6,7-dihydro-1H-pyrrolo[3,2-c]pyridin-4(5H)-one (0.065 g, 0.176 mmol, 40% yield, Example 238) as an orange solid: 1H NMR (400 MHz, DMSO-d6) δ ppm 12.11 (1H, br. s), 9.53 (1H, s), 8.12 (1H, d, J=9.0 Hz), 7.93 (1H, dt, J=7.4, 0.8 Hz), 7.56-7.71 (3H, m), 7.34-7.45 (2H, m), 7.29 (1H, t, J=7.6 Hz), 6.99-7.14 (2H, m), 6.85-6.98 (2H, m), 3.38-3.52 (1H, m), 2.86-3.08 (2H, m), 0.84 (3H, d, J=6.7 Hz). m/z (ESI, +ve) 369.1 (M+H)+. A portion of this material was resolved by chiral SFC (ChiralPak AS-H (21×250, 5 μm); additive in supercritical fluid CO2 was 40% MeOH with 20 mM NH3; 60 mL/min; column temperature 40° C.; outlet pressure 100 bar) to give separated enantiomers 7-methyl-2-(2-(phenylamino)quinolin-8-yl)-6,7-dihydro-1H-pyrrolo[3,2-c]pyridin-4(5H)-one (Example 29, first eluting enantiomer) and 7-methyl-2-(2-(phenylamino)quinolin-8-yl)-6,7-dihydro-1H-pyrrolo[3,2-c]pyridin-4(5H)-one (Example 30, second eluting anantiomer).
Reaction SMILES: CO[C:3](=[O:17])[C:4]([S:7][C:8]1[CH:13]=[C:12]([Cl:14])[CH:11]=[CH:10][C:9]=1[O:15]C)([CH3:6])[CH3:5].Br>>[Cl:14][C:12]1[CH:11]=[CH:10][C:9]2[O:15][C:3](=[O:17])[C:4]([CH3:5])([CH3:6])[S:7][C:8]=2[CH:13]=1
Reactant: COC(=O)C(C)(C)Sc1cc(Cl)ccc1OC
Agent: Br
Product: CC1(C)Sc2cc(Cl)ccc2OC1=O

Procedure:
To 2-(5-chloro-2-methoxy-phenylsulfanyl)-2-methyl-propionic acid methyl ester (prepared from 5-chloro-2-methoxy-benzenesulfonyl chloride: Syn. Comm., (2001), 31, 505–510) (0.25 g, 0.9 mmol) was added 48% hydrobromic acid (5 ml). The reaction was heated to reflux for 24 hours at which time the solvent was removed by evaporation. To the crude acid phenol was added toluene (5 ml) and catalytic pyridinium p-toluenesulfonate. After 12 hours of heating at reflux the reaction was concentrated and the title compound was isolated by chromatography on silica gel (0.27 g).
Reaction SMILES: [OH:1][C:2]1[CH:3]=[C:4]([C:9]2([S:15][CH3:16])[CH2:14][CH2:13][O:12][CH2:11][CH2:10]2)[CH:5]=[C:6]([F:8])[CH:7]=1.C[OH:18].O>>[OH:1][C:2]1[CH:3]=[C:4]([C:9]2([S:15]([CH3:16])=[O:18])[CH2:14][CH2:13][O:12][CH2:11][CH2:10]2)[CH:5]=[C:6]([F:8])[CH:7]=1
Reactant: CSC1(c2cc(O)cc(F)c2)CCOCC1
Reactant: CO
Solvent: O
Product: CS(=O)C1(c2cc(O)cc(F)c2)CCOCC1
Temperature: 25 °C
Reaction time: 2 h
Yield: 94 %

Procedure:
To a stirred solution of 4-(3-hydroxy-5-fluorophenyl)-4-methylthio-3,4,5,6-tetrahydro-2H-pyran (749 mg, 3.1 mmol)(EP 462830 A2 (1991)) in methanol-water (1:1.v/v; 20 ml) cooled to 0° C. was added NalO4 (710 mg, 3.3 mmol), the ice bath removed and the mixture stirred at room temperature for 2 hours. The reaction mixture was poured into water (50 ml) and extracted with ethyl acetate (50 ml). The organic extract was washed with water (50 ml), brine (50 ml), dried (MgSO4) and concentrated in vacuo. The residual solids were purified by column chromatography on silica gel (SiO2, 150 g; ethyl acetate) to afford 752 mg (94%) of the titled compound as white solids.
Reaction SMILES: [C:1]1([CH:8]=[CH:7][CH:6]=[C:4]([OH:5])[CH:3]=1)[OH:2].[C:9](OCC)(=[O:14])[CH2:10][C:11]([CH3:13])=O>C1(C)C(C)=CC=CC=1>[OH:2][C:1]1[CH:3]=[C:4]2[C:6]([C:11]([CH3:13])=[CH:10][C:9](=[O:14])[O:5]2)=[CH:7][CH:8]=1
Reactant: Oc1cccc(O)c1
Reactant: CCOC(=O)CC(C)=O
Solvent: Cc1ccccc1C
Product: Cc1cc(=O)oc2cc(O)ccc12
Temperature: 120 °C

Procedure:
To a 2 liter flask, a reaction mixture of 55 g (0.5 mole) resorcinol, 71.5 g (1.3 mole) ethyl acetoacetate, 200 g xylene, and 10 g Amberlyst 15 (Rohm and Haas) ion exchange resin catalyst was charged. With heating to a strong reflux at 110-130° C., a Von Pechman condensation reaction was carried out between resorcinol and ethyl acetoacetate to yield 7-hydroxy-4-methyl coumarine product.
Reaction SMILES: [OH-].[Na+].[Cl:3][C:4]1[C:12]2[O:11][CH:10]([C:13]([O:15]CC)=[O:14])[O:9][C:8]=2[CH:7]=[C:6]([C:18]([C:20]2[N:24]([CH3:25])[N:23]=[CH:22][CH:21]=2)=[O:19])[C:5]=1[Cl:26]>O.C(O)C>[Cl:3][C:4]1[C:12]2[O:11][CH:10]([C:13]([OH:15])=[O:14])[O:9][C:8]=2[CH:7]=[C:6]([C:18]([C:20]2[N:24]([CH3:25])[N:23]=[CH:22][CH:21]=2)=[O:19])[C:5]=1[Cl:26]
Reactant: CCOC(=O)C1Oc2cc(C(=O)c3ccnn3C)c(Cl)c(Cl)c2O1
Agent: [Na+]
Agent: [OH-]
Solvent: CCO
Solvent: O
Product: Cn1nccc1C(=O)c1cc2c(c(Cl)c1Cl)OC(C(=O)O)O2
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 96.5 %

Procedure:
A solution of 0.36 g of sodium hydroxide in 15 ml of water is added to a suspension of 1.86 g of ethyl 4,5-dichloro-6-(1-methyl-5-pyrazolylcarbonyl)-1,3-benzodi oxole-2-carboxylate in 35 ml of ethanol and the mixture is stirred at room temperature for 0.5 hour. The reaction mixture is concentrated to remove ethanol and adjusted to pH 1 with aqueous 10% hydrochloric acid. The resultant crystals are collected by filtration, washed successively with water and isopropyl ether and dried to give 1.66 g of 4,5-dichloro-6-(1-methyl-5-pyrazolylcarbonyl)-1,3-benzodioxole-2-carboxylic acid. Yield: 97%
Reaction SMILES: C1C(=O)N([Br:8])C(=O)C1.[Cl:9][C:10]([Cl:20])([Cl:19])[C:11]([C:13]1[N:14]([CH3:18])[CH:15]=[CH:16][CH:17]=1)=[O:12]>C1COCC1>[Br:8][C:16]1[CH:17]=[C:13]([C:11](=[O:12])[C:10]([Cl:9])([Cl:19])[Cl:20])[N:14]([CH3:18])[CH:15]=1
Reactant: Cn1cccc1C(=O)C(Cl)(Cl)Cl
Reactant: O=C1CCC(=O)N1Br
Solvent: C1CCOC1
Product: Cn1cc(Br)cc1C(=O)C(Cl)(Cl)Cl
Reaction time: 2 h
Yield: 87.8 %

Procedure:
NBS (N-Bromosuccinimide, 2.36 g, 13.24 mmol, 1.0 equiv.) was added to a stirred solution of 2-(trichloroacetyl)-1-methylpyrrole (2) (3 g, 13.24 mmol, 1.0 equiv.) in anhydrous THF (35 mL) at −10° C. The reaction mixture was kept at −10° C. for 2 hours and then left to reach room temperature (ca. 4 hours). Excess THF was evaporated in vacuum and the solid was re-dissolved in a mixture of EtOAc/n-hexane (1:9). The resulting mixture was filtered through a plug of silica, and the filtrate was evaporated in vacuo. The resulting solid was recrystallised from n-hexane to give 3 (3.55 g, 88%). IR (FTIR, vmax/cm−1): 3148, 2956, 1669 (C═O), 1458, 1215, 1189, 1062, 923, 842, 823, 748, 678; 1H-NMR (CDCl3, 400 MHz) δ 7.46 (1H, d, J=2.0 Hz), 6.95 (1H, d, J=1.6 Hz) 3.95 (3H, s); 13C NMR (CDCl3, 100 MHz): δ 172.4, 132.8, 124.6, 132.2, 96.1, 38.7; EIMS m/z (+EI) calc. for C7H5BrCl3NO (M)+ 305.38, LCMS analysis found 306.86 (M+H)+