Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:13]([CH3:14])=[N:12][NH:11][C:10](=O)[C:9]=2[C:16]2[CH:21]=[C:20]([F:22])[CH:19]=[C:18]([F:23])[C:17]=2[F:24])=[CH:4][CH:3]=1.P(Cl)(Cl)([Cl:27])=O>>[Cl:27][C:10]1[N:11]=[N:12][C:13]([CH3:14])=[C:8]([C:5]2[CH:6]=[CH:7][C:2]([Cl:1])=[CH:3][CH:4]=2)[C:9]=1[C:16]1[CH:21]=[C:20]([F:22])[CH:19]=[C:18]([F:23])[C:17]=1[F:24]
Reactant: Cc1n[nH]c(=O)c(-c2cc(F)cc(F)c2F)c1-c1ccc(Cl)cc1
Reactant: O=P(Cl)(Cl)Cl
Product: Cc1nnc(Cl)c(-c2cc(F)cc(F)c2F)c1-c1ccc(Cl)cc1
Temperature: 110 °C
Reaction time: 1 h
Yield: 96.6 %

Procedure:
1.80 g of 5-(4-chlorophenyl)-6-methyl-4-(2,3,5-trifluorophenyl)-2H-pyridazin-3-one and 10 g of phosphorus oxychloride were mixed and stirred at 110° C. for 1 hour. The reaction mixture was allowed to cool down to room temperature and concentrated under reduced pressure. To the residue was added ethyl acetate and ice water, and was separated to two layer. The organic layer was washed sequentially with water and saturated brine, and dried over anhydrous sodium sulfate, then, concentrated under reduced pressure, to obtain 1.83 g of 3-chloro-5-(4-chlorophenyl)-6-methyl-4-(2,3,5-trifluorophenyl)pyridazine (hereinafter, referred to as compound (viii) of the present invention).
Reaction SMILES: [CH2:1]([O:17][CH2:18][C:19](=[CH2:25])[C:20](OCC)=[O:21])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH3:16].CC(C[AlH]CC(C)C)C.S([O-])([O-])(=O)=O.[Na+].[Na+]>CCOCC>[CH2:1]([O:17][CH2:18][C:19](=[CH2:25])[CH2:20][OH:21])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH3:16]
Reactant: C=C(COCCCCCCCCCCCCCCCC)C(=O)OCC
Agent: CC(C)C[AlH]CC(C)C
Agent: O=S(=O)([O-])[O-]
Agent: [Na+]
Solvent: CCOCC
Product: C=C(CO)COCCCCCCCCCCCCCCCC
Temperature: 25 °C
Reaction time: 2 h
Yield: 139.4 %

Procedure:
To a solution of 21 g of ethyl 2-[(hexadecyloxy)methyl]-2-propenoate in 400 ml of ether cooled to 0° C. under an inert atmosphere is added 2.25 ml of 1,2M DIBAL in hexanes over 30 minutes. The reaction is stirred at ambient temperature for 2 hours then cooled to 0° C. while 20 ml of saturated sodium sulfate is added dropwise. After filtering, the cake is washed with ether. The combined ether washings are dried and the solvent removed. The residue is crystallized from methyl alcohol:water to give 25.8 g of the desired product as a colorless solid.
Reaction SMILES: [CH:1]1[C:6]([C:7]2[C:16](=[O:17])[C:15]3[C:14]([OH:18])=[CH:13][C:12]([OH:19])=[CH:11][C:10]=3[O:9][CH:8]=2)=[CH:5][CH:4]=[C:3]([OH:20])[CH:2]=1.C([O-])=O.[NH4+]>>[OH:18][C:14]1[CH:13]=[C:12]([OH:19])[CH:11]=[C:10]2[C:15]=1[C:16](=[O:17])[CH:7]([C:6]1[CH:5]=[CH:4][C:3]([OH:20])=[CH:2][CH:1]=1)[CH2:8][O:9]2
Reactant: O=c1c(-c2ccc(O)cc2)coc2cc(O)cc(O)c12
Agent: O=C[O-]
Agent: [NH4+]
Product: O=C1c2c(O)cc(O)cc2OCC1c1ccc(O)cc1
Yield: 52.9 %

Procedure:
Compound 22 was prepared following the general procedure described by Wähälä K. and Hase T. A., Heterocycles 28:183-86 (1989), herein incorporated by reference in its entirety. To a 50 mL round bottom flask was added genistein (270 mg, 1 mmol) and ammonium formate (1.08 g, 4 mmol). The flask was purged with N2, followed by addition of methanol (20 mL) and 10% Pd/C (255 mg). Upon consumption of the starting material (measured by reverse phase HPLC), the reaction mixture was passed through a pad of silica gel with EtOAc/Hex as the eluent. The solvent was concentrated in vacuo to afford crude 22. Purified by recrystallization from CHCl3/MeOH to afford 22 (144 mg, 53%) as brown crystals. Analytical data for isoflavanone 22: 1H NMR (500 MHz, DMSO) δ 12.19 (s, 1H), 10.84 (br s, 1H), 9.42 (br s, 1H), 7.08 (d, J=8.5 Hz, 2H), 6.73 (d, J=8.5 Hz, 2H), 5.91-5.90 (s, 2H), 4.53 (d, J=6.5 Hz, 2H), 4.00 (t, J=6.5 Hz, 1H); 13C NMR (125 MHz, DMSO) δ 197.6, 167.4, 164.6, 163.6, 157.4, 130.4, 126.3, 116.0, 102.5, 96.9, 95.5, 49.9; LCMS: Mass calculated for C15H12O5, [M+H]+, 273. Found 273.
Reaction SMILES: [CH3:1][O:2][C:3](=[O:26])[CH2:4][C:5]1[C:14]([CH3:15])=[C:13](B2OC(C)(C)C(C)(C)O2)[C:12]2[C:7](=[CH:8][CH:9]=[C:10]([F:25])[CH:11]=2)[CH:6]=1.Br[C:28]1[CH:33]=[CH:32][C:31]([S:34][C:35]2[CH:40]=[C:39]([F:41])[CH:38]=[C:37]([F:42])[CH:36]=2)=[CH:30][CH:29]=1.C(=O)(O)[O-].[Na+].O>C(COC)OC.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH3:1][O:2][C:3](=[O:26])[CH2:4][C:5]1[C:14]([CH3:15])=[C:13]([C:28]2[CH:29]=[CH:30][C:31]([S:34][C:35]3[CH:40]=[C:39]([F:41])[CH:38]=[C:37]([F:42])[CH:36]=3)=[CH:32][CH:33]=2)[C:12]2[C:7](=[CH:8][CH:9]=[C:10]([F:25])[CH:11]=2)[CH:6]=1
Reactant: Fc1cc(F)cc(Sc2ccc(Br)cc2)c1
Reactant: COC(=O)Cc1cc2ccc(F)cc2c(B2OC(C)(C)C(C)(C)O2)c1C
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: COCCOC
Solvent: O
Product: COC(=O)Cc1cc2ccc(F)cc2c(-c2ccc(Sc3cc(F)cc(F)c3)cc2)c1C
Yield: 36.2 %

Procedure:
A stirred solution of [6-fluoro-3-methyl-4-(4,4,5,5-tetra methyl-[1,3,2]-dioxaborolan-2-yl)-naphthalen-2-yl]-acetic acid methyl ester (0.2 g, 0.55 mmol) in dimethoxyethane (5 mL) was purged with argon for 5 minutes at room temperature. Tetrakis(triphenylphosphine)palladium(0) (0.032 g, 0.028 mmol), impure 1-(4-bromo-phenylsulfanyl)-3,5-difluorobenzene (0.184 g) and 1.0 M aqueous sodium bicarbonate (5 mL, 5 mmol) were added simultaneously to the reaction mixture under argon. The reaction mixture was refluxed for 2 hours and then brought to room temperature. Water was added and the resulting mixture was extracted twice with ethyl acetate. The combined organic extracts were washed with water and brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure to give the crude product, which was finally purified using flash chromatography (0-3% ethyl acetate in hexanes) to give {4-[4-(3,5-difluoro-phenylsulfanyl)-phenyl]-6-fluoro-3-methyl-naphthalen-2-yl}-acetic acid methyl ester (0.09 g, 36%) as a solid. MS calcd. for C26H18F3O2S [(M−H)−] 451, obsd. 451.2.
Reaction SMILES: [NH2:1][C:2]([CH3:6])([CH3:5])[CH2:3][OH:4].[C:7](Cl)(=[O:14])[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1>ClCCl>[C:7]([NH:1][C:2]([CH3:6])([CH3:5])[CH2:3][OH:4])(=[O:14])[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1
Reactant: CC(C)(N)CO
Reactant: O=C(Cl)c1ccccc1
Solvent: ClCCl
Product: CC(C)(CO)NC(=O)c1ccccc1
Temperature: 25 °C

Procedure:
To a 250 ml dichloromethane solution containing 89 g (1.0 mol) 2-amino-2-methyl-1-propanol at 0° was added dropwise with stirring 70 g (0.5 mol) benzoyl chloride in 250 ml dichloromethane. The reaction mixture was warmed to room temperature and stirred for several hours. The 2-amino-2-methyl-1-propanol hydrochloride was removed from the reaction mixture by filtration and was thoroughly washed with dichloromethane. The filtrate and washings were combined and the dichloromethane removed under reduced pressure to afford 67.55 g (0.35 mol), 70%, 2-benzoylamino-2-methyl-1-propanol as a white solid, mp 80°-82°, sublimation at 75° (0.2 mm); ir (KBr) 1630 (c=o) cm-1 ; pmr (CDCl3) δ 1.50 (s, 6H), 3.67 (s, 2H), 5.27 (bs, 1H), 6.92 (bs, 1H) and 7.1-8.3 (m, 5H) ppm.
Reaction SMILES: Br[C:2]1[N:3]=[C:4]([C:22]([F:25])([F:24])[F:23])[N:5]2[CH:10]=[C:9]([C:11]3[CH:16]=[CH:15][C:14]([O:17][C:18]([F:21])([F:20])[F:19])=[CH:13][CH:12]=3)[CH:8]=[CH:7][C:6]=12.[Li][C:27](C)(C)C.CI.O>CCOCC>[CH3:27][C:2]1[N:3]=[C:4]([C:22]([F:25])([F:24])[F:23])[N:5]2[CH:10]=[C:9]([C:11]3[CH:16]=[CH:15][C:14]([O:17][C:18]([F:21])([F:20])[F:19])=[CH:13][CH:12]=3)[CH:8]=[CH:7][C:6]=12
Reactant: [Li]C(C)(C)C
Reactant: FC(F)(F)Oc1ccc(-c2ccc3c(Br)nc(C(F)(F)F)n3c2)cc1
Solvent: CCOCC
Solvent: CI
Solvent: O
Product: Cc1nc(C(F)(F)F)n2cc(-c3ccc(OC(F)(F)F)cc3)ccc12
Temperature: -78 °C

Procedure:
1-bromo-6-(4-(trifluoromethoxy)phenyl)-3-(trifluoromethyl)imidazo[1,5-a]pyridine (50.0 mg, 0.118 mmol) was dissolved in ether (2 mL) in a 50 mL round bottomed flask under a nitrogen atmosphere. The solution was cooled down to −78° C. and treated with t-BuLi (1.7 M pentane solution, 0.15 mL, 0.255 mmol, 2.2 equiv.) for 5 min. To the mixture was added a solution of MeI (65.8 mg, 0.464 mmol, 4.0 equiv.) in ether (1 mL). The reaction was allowed to warm up to room temperature for 30 min. To the mixture was added H2O (30 mL) and the whole was extracted with EtOAc (30 mL×3). Combined organic layers were washed with brine (30 mL) and dried with Na2SO4. The solvent was removed under a reduced pressure to give a crude mixture. The crude mixture was purified by a preparative TLC (SiO2=1 plate, ether/hexane=1:3 Rf=0.4) to give 1-methyl-6-(4-(trifluoromethoxy)phenyl)-3-(trifluoromethyl)imidazo[1,5-a]pyridine as light yellow crystals.
Reaction SMILES: [CH2:1]([C:5]1[N:6]([CH2:23][C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=2[Cl:30])[C:7](/[CH:10]=[C:11](\[CH2:16][C:17]2[CH:22]=[CH:21][N:20]=[CH:19][CH:18]=2)/[C:12]([O:14]C)=[O:13])=[CH:8][N:9]=1)[CH2:2][CH2:3][CH3:4].[OH-].[Na+]>C(O)C>[CH2:1]([C:5]1[N:6]([CH2:23][C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=2[Cl:30])[C:7](/[CH:10]=[C:11](\[CH2:16][C:17]2[CH:18]=[CH:19][N:20]=[CH:21][CH:22]=2)/[C:12]([OH:14])=[O:13])=[CH:8][N:9]=1)[CH2:2][CH2:3][CH3:4]
Reactant: CCCCc1ncc(/C=C(\Cc2ccncc2)C(=O)OC)n1Cc1ccccc1Cl
Agent: [Na+]
Agent: [OH-]
Solvent: CCO
Product: CCCCc1ncc(/C=C(\Cc2ccncc2)C(=O)O)n1Cc1ccccc1Cl
Temperature: 25 °C
Reaction time: 18 h
Yield: 16 %

Procedure:
A solution of methyl (E)-3-[2-n-butyl-1-{(2-chlorophenyl)methyl}-1H-imidazol-5-yl]-2-(4-pyridyl)methyl-2-propenoate (3.1 g, 7.3 mmol) in ethanol (16 mL) was treated with 10% sodium hydroxide solution and the mixture was stirred for 18 hours at 25° C. The solution was concentrated in vacuum, water was added, the pH was adjusted to 6.5 and the resulting solid was filtered, washed with water and crystallized from methanol/ether to afford 0.48 g of (E)-3-[2-n-butyl-1-{(2-chlorophenyl)methyl}-1H-imidazol-5-yl]-2-(4-pyridyl)methyl-2-propenoic acid; mp 178°-182° C. (d).
Reaction SMILES: [C:1](N1C=CN=C1)(N1C=CN=C1)=[O:2].[NH2:13][CH2:14][CH2:15][CH2:16][NH:17][C:18]1([CH2:31][OH:32])[CH2:23][CH2:22][N:21]([CH2:24][C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)[CH2:20][CH2:19]1>C1COCC1>[OH:32][CH2:31][C:18]1([N:17]2[CH2:16][CH2:15][CH2:14][NH:13][C:1]2=[O:2])[CH2:19][CH2:20][N:21]([CH2:24][C:25]2[CH:26]=[CH:27][CH:28]=[CH:29][CH:30]=2)[CH2:22][CH2:23]1
Reactant: NCCCNC1(CO)CCN(Cc2ccccc2)CC1
Reactant: O=C(n1ccnc1)n1ccnc1
Solvent: C1CCOC1
Product: O=C1NCCCN1C1(CO)CCN(Cc2ccccc2)CC1
Temperature: 25 °C
Reaction time: 8 h
Yield: 49.3 %

Procedure:
1,1′-Carbonylbis-1H-imidazole (0.0149 mol) was added to a mixture of intermediate (15) (0.0137 mol) in THF (40 ml). The mixture was stirred at room temperature overnight. The precipitate was filtered off, crystallized from ACN, filtered off, washed with ACN and DIPE and then dried, yielding 2.05 g of tetrahydro-1-[4-(hydroxy-methyl)-1-(phenylmethyl)4-piperidinyl]-2(1H)-pyrimidinone (intermediate 16, mp. 210° C.).
Reaction SMILES: [NH2:1][C@H:2]([C:13]([OH:15])=[O:14])[CH2:3][C:4]1[C:12]2[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=2)[NH:6][CH:5]=1.[CH2:16]=O>>[CH2:16]1[C:5]2[NH:6][C:7]3[C:12]([C:4]=2[CH2:3][CH:2]([C:13]([OH:15])=[O:14])[NH:1]1)=[CH:11][CH:10]=[CH:9][CH:8]=3
Reactant: N[C@@H](Cc1c[nH]c2ccccc12)C(=O)O
Reactant: C=O
Product: O=C(O)C1Cc2c([nH]c3ccccc23)CN1

Procedure:
To a mixture of 0.1 NH2SO4 (150 mL) and 37% formaldehyde (80 mL) was added portionwise L-tryptophane (50 g, 245 mmol) with stirring. After being stirred for 4 h at room temperature, the white solid separated out was collected by filtration. The solid cake was washed with water and dried to give 1,2,3,4-tetrahydro-pyrido[3,4-b]indole-3-carboxylic acid, 41 g, (78%); mp 275-276° C. (lit.18 mp 280-282° C.). 1H NMR (DMSO-d6) δ 2.84 (1H, m, CH2), 3.16 (1H, m, CH2), 3.66 (1H, m, CH2), 4.23 (1H, m, CH2), 4.38 (1H, m, CH), 6.98-7.02 (1H, m, ArH), 7.13-7.16 (1H, m, ArH), 7.32-7.34 (1H, m, ArH), 7.45-7.48 (1H, m, ArH), 11.03 (1H, brs, exchangeable, NH).
Reaction SMILES: I[C:2]1[CH:19]=[CH:18][C:5]2[N:6]([CH2:11][CH2:12][N:13]3[CH2:17][CH2:16][CH2:15][CH2:14]3)[C:7](=[O:10])[N:8]([CH3:9])[C:4]=2[CH:3]=1.[Cl:20][C:21]1[CH:26]=[CH:25][C:24]([C:27]2[CH:28]=[CH:29][C:30]([C:33]#[CH:34])=[N:31][CH:32]=2)=[CH:23][CH:22]=1>>[Cl:20][C:21]1[CH:22]=[CH:23][C:24]([C:27]2[CH:28]=[CH:29][C:30]([C:33]#[C:34][C:2]3[CH:19]=[CH:18][C:5]4[N:6]([CH2:11][CH2:12][N:13]5[CH2:17][CH2:16][CH2:15][CH2:14]5)[C:7](=[O:10])[N:8]([CH3:9])[C:4]=4[CH:3]=3)=[N:31][CH:32]=2)=[CH:25][CH:26]=1
Reactant: C#Cc1ccc(-c2ccc(Cl)cc2)cn1
Reactant: Cn1c(=O)n(CCN2CCCC2)c2ccc(I)cc21
Product: Cn1c(=O)n(CCN2CCCC2)c2ccc(C#Cc3ccc(-c4ccc(Cl)cc4)cn3)cc21

Procedure:
Prepared according to general working method I from 5-iodo-3-methyl-1-(2-pyrrolidin-1-yl-ethyl)-1,3-dihydro-benzimidazol-2-one (120 mg, 0.32 mmol) and 5-(4-chloro-phenyl)-2-ethynyl-pyridine (68 mg, 0.32 mmol).
Reaction SMILES: [H-].[Na+].Br[CH2:4][C:5]1[CH:15]=[CH:14][C:8]([C:9]([O:11][CH2:12][CH3:13])=[O:10])=[CH:7][CH:6]=1.C(OP(OCC)OCC)C.[CH:26](=O)[C:27]1[O:31][CH:30]=[CH:29][CH:28]=1>O1CCCC1>[CH2:12]([O:11][C:9](=[O:10])[C:8]1[CH:14]=[CH:15][C:5](/[CH:4]=[CH:26]/[C:27]2[O:31][CH:30]=[CH:29][CH:28]=2)=[CH:6][CH:7]=1)[CH3:13]
Reactant: O=Cc1ccco1
Reactant: CCOC(=O)c1ccc(CBr)cc1
Agent: CCOP(OCC)OCC
Agent: [H-]
Agent: [Na+]
Solvent: C1CCOC1
Product: CCOC(=O)c1ccc(/C=C/c2ccco2)cc1
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 42 %

Procedure:
60% Sodium hydride (0.48 g, 12 mmol) was suspended in anhydrous tetrahydrofuran (10 mL) under nitrogen atmosphere, and diethyl 4-ethoxycarbonyl benzylphosphonate (3.6 g, 12 mmol) prepared from ethyl 4-bromomethylbenzoate and triethylphosphite according to the methods as similar to those of Manufacturing Example 93-1-1 was added at room temperature and stirred for 30 minutes at room temperature. Furfural (1 g, 10.4 mmol) was then added at room temperature, and stirred for 2 hours at room temperature. The reaction mixture was partitioned into water and ethyl acetate on an ice bath (0° C.). The organic layer was washed with water and saturated aqueous sodium chloride and dried over anhydrous magnesium sulfate, and the solvent was evaporated under a reduced pressure. The residue was purified by NH silica gel column chromatography (ethyl acetate:heptane=1:20) to obtain the title compound (1.07 g, 42%).
Reaction SMILES: Cl[CH2:2][CH2:3][CH2:4][N:5]1[CH2:10][CH2:9][CH:8]([CH:11]([C:20]2[CH:25]=[CH:24][C:23]([F:26])=[CH:22][CH:21]=2)[NH:12][C:13]2[CH:18]=[CH:17][C:16]([F:19])=[CH:15][CH:14]=2)[CH2:7][CH2:6]1.[NH2:27][C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1>>[F:19][C:16]1[CH:17]=[CH:18][C:13]([NH:12][CH:11]([C:20]2[CH:25]=[CH:24][C:23]([F:26])=[CH:22][CH:21]=2)[CH:8]2[CH2:9][CH2:10][N:5]([CH2:4][CH2:3][CH2:2][NH:27][C:28]3[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=3)[CH2:6][CH2:7]2)=[CH:14][CH:15]=1
Reactant: Fc1ccc(NC(c2ccc(F)cc2)C2CCN(CCCCl)CC2)cc1
Reactant: Nc1ccccc1
Product: Fc1ccc(NC(c2ccc(F)cc2)C2CCN(CCCNc3ccccc3)CC2)cc1

Procedure:
1-(3-Chloropropyl)-N,α-bis(4-fluorophenyl)-4-piperidinemethanamine and excess aniline are heated together until the reaction is complete. Excess aniline is distilled off and the residual material partitioned between dilute aqueous sodium hydroxide and methylene chloride. The methylene chloride solution is dried and concentrated to obtain the title compound.
Reaction SMILES: [C:1]1([S:7]([N:10]2[C:25]([CH:26]=[CH2:27])=[C:14]3[CH2:15][CH:16]([N:22]([CH3:24])[CH3:23])[C:17]4[CH2:18][O:19][CH:20]=[CH:21][C:12]([C:13]=43)=[CH:11]2)(=[O:9])=[O:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1>CO.O1CCCC1.[Pd]>[C:1]1([S:7]([N:10]2[C:25]([CH2:26][CH3:27])=[C:14]3[CH2:15][CH:16]([N:22]([CH3:23])[CH3:24])[C:17]4[CH2:18][O:19][CH:20]=[CH:21][C:12]([C:13]=43)=[CH:11]2)(=[O:9])=[O:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: C=CC1=C2CC(N(C)C)C3=C2C(=CN1S(=O)(=O)c1ccccc1)C=COC3
Agent: [Pd]
Solvent: CO
Solvent: C1CCOC1
Product: CCC1=C2CC(N(C)C)C3=C2C(=CN1S(=O)(=O)c1ccccc1)C=COC3
Temperature: 25 °C
Reaction time: 18 h
Yield: 98.4 %

Procedure:
Compound (54) 200.1 mg was dissolved in a mixture of methanol 8 ml and tetrahydrofuran 4 ml. 10% Pd/C 49.8 mg was added. The mixture was stirred under hydrogen atmosphere for 18 h at room temperature. The catalyst was filtered off and the filtrate was concentrated under reduced pressure. The residue obtained was chromatographed on aluminum oxide in chloroform:hexane (1:1) to give the titled compound as a colorless oil 198 mg. Yield 98%. This was treated with 1 eq. of oxalic acid to give the salt, which was recrystallized from ether-methanol to give colorless crystals, m.p. 193-194° C.(dec.).
Reaction SMILES: [CH3:1][C:2]1([C:11](=[O:13])[CH3:12])[CH2:10][C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[CH2:3]1.[Br:14]Br>C(Cl)Cl>[Br:14][CH2:12][C:11]([C:2]1([CH3:1])[CH2:10][C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[CH2:3]1)=[O:13]
Reactant: BrBr
Reactant: CC(=O)C1(C)Cc2ccccc2C1
Solvent: ClCCl
Product: CC1(C(=O)CBr)Cc2ccccc2C1

Procedure:
1-(2,3-Dihydro-2-methyl-1H-inden-2-yl)ethanone (3.69 g) in methylene chloride (40 ml) is stirred and cooled at 10° C. during the dropwise addition of bromine (2.82 g)/methylene chloride (10 ml). Work-up of the resultant solution gives 2-bromo-1-(2,3-dihydro-2-methyl-1H-inden-2-yl)ethanone.
Reaction SMILES: [OH:1][C:2]1[CH:3]=[N:4][CH:5]=[CH:6][CH:7]=1.[CH2:8]1[CH2:12][O:11][CH2:10]C1>CS(C)=O>[N:4]1[CH:5]=[CH:6][CH:7]=[C:2]([O:1][CH2:8][C@@H:12]2[CH2:10][O:11]2)[CH:3]=1
Reactant: Oc1cccnc1
Reactant: C1CCOC1
Solvent: CS(C)=O
Product: c1cncc(OC[C@@H]2CO2)c1
Temperature: 25 °C
Reaction time: 0.08 h
Yield: 51 %

Procedure:
To a solution of 11.9 g (0.125 mol) of 3-hydroxypyridine in 50 mL of DMSO at 15° C. was added 120 mL (0.12 mol) of a 1.0 M solution of sodium hexamethyldisilylazide in THF. After the reaction mixture was allowed to stir for 5 min, 25.9 g (0.10 mol) of (2S)-glycidyl 3-nitrobenzene sulfonate was added in one portion. The mixture was cooled with a room temperature water bath for 30 min. It s was then quenched by the addition of 250 mL of water and extracted with three portions of ethyl acetate. The combined aqueous extracts were washed sequentially with water and brine, dried over sodium sulfate, treated with granular charcoal, filtered and concentrated to give 7.7 g (51%) of an orange oil which was used without further purification. An analytical sample was prepared by flash chromatography (silica gel, 80% ethyl acetate/hexane): 1H NMR (400 MHz, CDCl3) a 8.31 (m, 1H), 8.21 (m, 1H), 7.20-7.22 (m, 2H), 4.29 (dd, 1H, J=1,6 Hz), 3.95 (m, 1H), 3.34 (m, 1H), 2.90 (t, 1H, J=3Hz), 2.75 (m, 1H).
Reaction SMILES: [Cl-].[Cl-].[Cl-].[Al+3].[C:5](Cl)(=[O:11])[CH2:6][CH2:7][CH2:8][CH2:9][CH3:10].[S:13]([N:23]1[C:31]2[C:26](=[CH:27][CH:28]=[CH:29][CH:30]=2)[CH:25]=[CH:24]1)([C:16]1[CH:22]=[CH:21][C:19]([CH3:20])=[CH:18][CH:17]=1)(=[O:15])=[O:14]>ClCCl>[C:5]([C:25]1[C:26]2[C:31](=[CH:30][CH:29]=[CH:28][CH:27]=2)[N:23]([S:13]([C:16]2[CH:22]=[CH:21][C:19]([CH3:20])=[CH:18][CH:17]=2)(=[O:15])=[O:14])[CH:24]=1)(=[O:11])[CH2:6][CH2:7][CH2:8][CH2:9][CH3:10]
Reactant: Cc1ccc(S(=O)(=O)n2ccc3ccccc32)cc1
Reactant: CCCCCC(=O)Cl
Agent: [Al+3]
Agent: [Cl-]
Solvent: ClCCl
Product: CCCCCC(=O)c1cn(S(=O)(=O)c2ccc(C)cc2)c2ccccc12
Temperature: 5 °C
Reaction time: 0.17 h
Yield: 78.4 %

Procedure:
Aluminium trichloride (6.01 g, 45.2 mmol), is suspended in dichloromethane (80 cm3), under nitrogen. A solution of hexanoyl chloride (5a) (6.62 g, 49.2 mmol) in dichloromethane (20 cm3) is added slowly to the stirred mixture at ambient temperature. After the addition is complete, the mixture is stirred for a further 10 minutes. The reaction mixture is cooled to 5° C. 1-tosylindole (4) (45.2 mmol, 12.24 g) in dichloromethane (20 cm3) is added to the mixture while the temperature is maintained at 5° C. After two hours stirring at room temperature the reaction mixture is treated with ice water, extracted with dichloromethane and dried over magnesium sulphate. Evaporation of the solvent gives a thick oil, which crystallises in the presence of methanol and dichloromethane to yield colourless crystals of 3-hexanoyl-1-tosylindole (6a) (13.07 g, 35.42 mmol, 78%), m.p. 91-93° C.
Reaction SMILES: Br[C:2]1[CH:3]=[C:4]([S:8]([N:11]2[C:15]([C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=3)=[CH:14][C:13]([CH2:22][N:23]([CH3:31])C(=O)OC(C)(C)C)=[CH:12]2)(=[O:10])=[O:9])[CH:5]=[N:6][CH:7]=1.C(N(CC)CC)C.CO.[C:41]([O:44][CH2:45]C)(=[O:43])C.[ClH:47]>C(O)C>[ClH:47].[CH3:31][NH:23][CH2:22][C:13]1[CH:14]=[C:15]([C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)[N:11]([S:8]([C:4]2[CH:5]=[N:6][CH:7]=[C:2]([CH:3]=2)[C:41]([O:44][CH3:45])=[O:43])(=[O:10])=[O:9])[CH:12]=1
Reactant: CN(Cc1cc(-c2ccccc2)n(S(=O)(=O)c2cncc(Br)c2)c1)C(=O)OC(C)(C)C
Reactant: CCOC(C)=O
Agent: Cl
Solvent: CCN(CC)CC
Solvent: CO
Solvent: CCO
Product: CNCc1cc(-c2ccccc2)n(S(=O)(=O)c2cncc(C(=O)OC)c2)c1
Temperature: 100 °C
Reaction time: 12 h
Yield: 56 %

Procedure:
A mixture of tert-butyl ({1-[(5-bromopyridin-3-yl)sulfonyl]-5-phenyl-1H-pyrrol-3-yl}methyl)methylcarbamate (112 mg), dichloro[bis(triphenylphosphine)]palladium (28 mg), triethylamine (0.25 mL) and methanol (15 mL) was stirred under a carbon monoxide atmosphere (3 atm) at 100° C. for 12 hr. After cooling to room temperature, the reaction mixture was concentrated under reduced pressure. A saturated aqueous sodium hydrogencarbonate solution was added to the residue, and the mixture was extracted with ethyl acetate. The extract was washed with saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: hexane-ethyl acetate=19:1→3:2) to give a colorless oil. The obtained oil was dissolved in ethanol (2 mL), and a 4 mol/L hydrogen chloride-ethyl acetate solution (2 mL) was added. After stirring at room temperature for 1 hr, the mixture was concentrated under reduced pressure, and recrystallized from ethanol to give the title compound as a solid (yield 47.0 mg, 56%).
Reaction SMILES: [CH3:1][O:2][C:3]([C:5]1([CH2:11][CH:12]=C)[CH2:10][CH2:9][CH2:8][CH2:7][CH2:6]1)=[O:4].I([O-])(=O)(=O)=[O:15].[Na+]>C(O)(C)C.O.[Os](=O)(=O)(=O)=O>[CH3:1][O:2][C:3]([C:5]1([CH2:11][CH:12]=[O:15])[CH2:10][CH2:9][CH2:8][CH2:7][CH2:6]1)=[O:4]
Reactant: [O-][I+3]([O-])([O-])[O-]
Reactant: C=CCC1(C(=O)OC)CCCCC1
Agent: O=[Os](=O)(=O)=O
Agent: [Na+]
Solvent: CC(C)O
Solvent: O
Product: COC(=O)C1(CC=O)CCCCC1
Reaction time: 24 h
Yield: 31 %

Procedure:
To a solution of 1-allyl-cyclohexanecarboxylic acid methyl ester (4.0 g, 21.5 mmol) in isopropanol (35 mL) was added a solution of sodium periodate (10.1 g, 47.3 mmol) in H2O (35 mL) followed by the addition of osmium tetroxide (16 mg, 0.065 mmol). More isopropanol (30 mL) and H2O (35 mL) was added and the resulting suspension was stirred for 24 hours. Then, the reaction mixture was poured into ice/H2O (200 mL) and extracted with EtOAc (2×200 mL) in a separatory funnel. The organic layers were combined and dried over Na2SO4, filtered and concentrated to provide a crude oil which was purified by flash column chromatography (10 to 60% EtOAc/heptane) to provide 1.24 g (31% yield over two steps) of the title compound as an oil.
Reaction SMILES: [N:1]([C:4]1[CH:5]=[CH:6][C:7]([CH3:28])=[C:8]([C:10]([C:12]2[CH:17]=[CH:16][C:15]([NH:18][C:19]3[CH:24]=[CH:23][C:22]([O:25][CH3:26])=[CH:21][CH:20]=3)=[CH:14][C:13]=2[Cl:27])=[O:11])[CH:9]=1)=[N+:2]=[N-:3].[CH2:29]([OH:33])[CH2:30][C:31]#[CH:32]>>[Cl:27][C:13]1[CH:14]=[C:15]([NH:18][C:19]2[CH:24]=[CH:23][C:22]([O:25][CH3:26])=[CH:21][CH:20]=2)[CH:16]=[CH:17][C:12]=1[C:10]([C:8]1[CH:9]=[C:4]([N:1]2[CH:32]=[C:31]([CH2:30][CH2:29][OH:33])[N:3]=[N:2]2)[CH:5]=[CH:6][C:7]=1[CH3:28])=[O:11]
Reactant: COc1ccc(Nc2ccc(C(=O)c3cc(N=[N+]=[N-])ccc3C)c(Cl)c2)cc1
Reactant: C#CCCO
Product: COc1ccc(Nc2ccc(C(=O)c3cc(-n4cc(CCO)nn4)ccc3C)c(Cl)c2)cc1

Procedure:
The reaction was carried out similarly as described in the preparation of compound 116, using compound 448 (0.03 mmol) and but-3-yn-1-ol (0.06 mmol). The crude product was purified by continuous gradient flash chromatography using EtOAc/petroleum ether (40-60) 30:70 to 100:0 as the eluent to afford the title compound. 13C NMR (CDCl3) δ 194.7, 157.3, 150.5, 146.2, 141.4, 138.1, 135.8, 134.6, 134.2, 132.5, 132.2, 126.5, 125.3, 122.1, 120.6, 120.1, 115.2, 115.0, 111.8, 61.5, 55.6, 28.6, 19.9