Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [I:1][C@@H:2]1[C@@H:15]([O:16]C(=O)C)[C@H:14]([O:20]C(=O)C)[C@@H:13]([CH2:24][O:25]C(=O)C)[O:12][C@H:3]1[O:4][Si:5]([CH2:10][CH3:11])([CH2:8][CH3:9])[CH2:6][CH3:7].C(=O)([O-])[O-].[K+].[K+]>C(Cl)(Cl)Cl.CO>[I:1][C@@H:2]1[C@@H:15]([OH:16])[C@H:14]([OH:20])[C@@H:13]([CH2:24][OH:25])[O:12][C@H:3]1[O:4][Si:5]([CH2:10][CH3:11])([CH2:6][CH3:7])[CH2:8][CH3:9]
Reactant: CC[Si](CC)(CC)O[C@@H]1O[C@H](COC(C)=O)[C@@H](OC(C)=O)[C@H](OC(C)=O)[C@H]1I
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: ClC(Cl)Cl
Solvent: CO
Product: CC[Si](CC)(CC)O[C@@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1I
Temperature: 25 °C
Yield: 18.7 %

Procedure:
Subsequently, the 2-deoxy-2-iodo-3,4,6-tri-O-acetyl-1-O-triethylsilyl-β-D-glucopyranose (III) (0.7 g) was dissolved in the mixture of chloroform:methanol (7:3 v/v) (15 mL). Potassium carbonate (4 g) was added, and reaction mixture was stirred at room temperature until substrate deacetylation has been completed. Inorganic salts were filtered off and solvents were evaporated. Such obtained product was purified by column chromatography (SilicaGel 60, Merck) using chloroform and chloroform:methanol 99:1 as eluents, to give (0.1 g) of 2-deoxy-2-iodo-1-O-triethylsilyl-β-D-glucopyranose (VI) (yield 20%).
Reaction SMILES: [CH2:1]([C:3]1[CH:4]=[CH:5][C:6]2[C:7]([CH:17]=1)=[C:8]([C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1)[O:9][N:10]=2)[CH3:2].[Br:18]N1C(=O)CCC1=O>C(Cl)(Cl)(Cl)Cl.C(OOC(=O)C1C=CC=CC=1)(=O)C1C=CC=CC=1>[Br:18][CH:1]([C:3]1[CH:4]=[CH:5][C:6]2[C:7]([CH:17]=1)=[C:8]([C:11]1[CH:12]=[CH:13][CH:14]=[CH:15][CH:16]=1)[O:9][N:10]=2)[CH3:2]
Reactant: CCc1ccc2noc(-c3ccccc3)c2c1
Reactant: O=C1CCC(=O)N1Br
Agent: O=C(OOC(=O)c1ccccc1)c1ccccc1
Solvent: ClC(Cl)(Cl)Cl
Product: CC(Br)c1ccc2noc(-c3ccccc3)c2c1
Reaction time: 1 h
Yield: 105.5 %

Procedure:
A mixture of 15.4 g (0.069 mole) of 5-ethyl-3-phenyl-2,1-benzisoxazole, 12.4 g (0.0697 mole) of N-bromosuccinimide and 0.3 g of dibenzoyl peroxide in 300 ml of carbon tetrachloride was heated at reflux under floodlight illumination and an argon atmosphere for one hr and then filtered while still hot. The filtrate was concentrated under reduced pressure to give 22.0 g of a semi-solid residue (NMR indicated 80% product). A sample of this semi-solid was triturated with 3 ml of methylene chloride and filtered. The solid filter cake was recrystallized from ethyl ether to give yellow solid, m.p. 118°-119° C. (with decomposition).
Reaction SMILES: Br[C:2]1[N:7]=[C:6]([CH:8]=[O:9])[CH:5]=[CH:4][CH:3]=1.[C:10]1([N:16]([CH2:24][C:25]2[CH:34]=[CH:33][C:32]3[C:27](=[CH:28][CH:29]=[CH:30][CH:31]=3)[C:26]=2B2OC(C)(C)C(C)(C)O2)[C:17](=[O:23])[O:18][C:19]([CH3:22])([CH3:21])[CH3:20])[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1>CO.O.C1(C)C=CC=CC=1.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>[CH:8]([C:6]1[N:7]=[C:2]([C:26]2[C:27]3[C:32](=[CH:31][CH:30]=[CH:29][CH:28]=3)[CH:33]=[CH:34][C:25]=2[CH2:24][N:16]([C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)[C:17](=[O:23])[O:18][C:19]([CH3:22])([CH3:20])[CH3:21])[CH:3]=[CH:4][CH:5]=1)=[O:9]
Reactant: O=Cc1cccc(Br)n1
Reactant: CC(C)(C)OC(=O)N(Cc1ccc2ccccc2c1B1OC(C)(C)C(C)(C)O1)c1ccccc1
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Solvent: Cc1ccccc1
Solvent: CO
Solvent: O
Product: CC(C)(C)OC(=O)N(Cc1ccc2ccccc2c1-c1cccc(C=O)n1)c1ccccc1
Temperature: 25 °C

Procedure:
A solution of 24.3 g (84.8 mmol) of Na2CO3(H2O)1 in a mixture of 120 ml of methanol and 450 ml of water was added to a mixture of 6.30 g (33.9 mmol) of 6-bromopyridine-2-carbaldehyde, 15.6 g (33.9 mmol) of tert-butyl phenyl{[1-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2-naphthyl]methyl}carbamate and 1.96 g (1.70 mmol) of Pd(PPh3)4 in 600 ml of toluene by vigorous stirring at room temperature. The resulting mixture was stirred at 80° C. for 12 h. Further on, this mixture was cooled to room temperature, the organic layer was separated, dried over MgSO4, and then evaporated to dryness. The product was isolated by flash chromatography on silica gel 60 (40-63 um; eluent: hexanes-ethyl acetate=50:1 and then 10:1, vol.). Yield 9.50 g (64%). Anal. calc. for C28H26N2O3: C, 76.69; H, 5.98; N, 6.39. Found: C, 76.87; H, 6.12; N, 6.25. 1H NMR (CDCl3): 10.03 (s, 1H, CHO), 7.94-7.98 (m, 2H, 3,5-H in Py), 7.88 (m, 1H, 8-H in naphthyl), 7.83 (m, 1H, 4-H in Py), 7.75 (d, J=8.6 Hz, 1H, 4-H in naphthyl), 7.45 (m, 1H, 7-H in naphthyl), 7.34 (m, 1H, 6-H in naphthyl), 7.11-7.18 (m, 4H, 5-H in naphthyl and 3,4,5-H in Ph), 7.03 (d, J=8.6 Hz, 1H, 3-H in naphthyl), 6.93 (m, 2H, 2,6-H in Ph), 5.06 (d, J=15.9 Hz, 1H, CHH′N), 4.52 (d, J=15.9 Hz, 1H, CHH′N), 1.40 (s, 9H, tBu).
Reaction SMILES: [CH3:1][O:2][C:3](=[O:12])[C:4]1[CH:9]=[C:8](Br)[CH:7]=[CH:6][C:5]=1[NH2:11].[Cu][C:14]#[N:15]>CN1CCCC1=O.O>[CH3:1][O:2][C:3](=[O:12])[C:4]1[CH:9]=[C:8]([C:14]#[N:15])[CH:7]=[CH:6][C:5]=1[NH2:11]
Reactant: COC(=O)c1cc(Br)ccc1N
Reactant: N#C[Cu]
Solvent: O
Solvent: CN1CCCC1=O
Product: COC(=O)c1cc(C#N)ccc1N
Temperature: 25 °C
Yield: 28.4 %

Procedure:
2-Amino-5-bromobenzoic acid methyl ester (4.6 g, 20 mmol) and copper (I) cyanide (3.6 g, 40 mmol) were heated at 200° C. in N-methylpyrrolidinone (20 ml) for 4 h. After cooling to room temperature, the solution was diluted with water, extracted with ethyl acetate, the aqueous extract acidified with 2N hydrochloric acid and filtered. The organic layer was separated, dried over magnesium sulphate and evaporated. The residue was purified by flash column chromatography on silica eluting with 50% ethyl acetate in hexane to yield the title compound as a colourless oil (1.0 g). MS (+EI) m /z 176 [M+ ].
Reaction SMILES: [O:1]1[CH2:6][CH2:5][N:4]([C:7]2[CH:12]=[CH:11][C:10]([C:13]3[CH:14]=[CH:15][C:16]4[S:22][CH2:21][CH2:20][C:19]([C:23]([O:25]C)=[O:24])=[CH:18][C:17]=4[CH:27]=3)=[CH:9][CH:8]=2)[CH2:3][CH2:2]1.[OH-].[Na+].Cl>C(O)C.C1COCC1>[O:1]1[CH2:2][CH2:3][N:4]([C:7]2[CH:12]=[CH:11][C:10]([C:13]3[CH:14]=[CH:15][C:16]4[S:22][CH2:21][CH2:20][C:19]([C:23]([OH:25])=[O:24])=[CH:18][C:17]=4[CH:27]=3)=[CH:9][CH:8]=2)[CH2:5][CH2:6]1
Reactant: COC(=O)C1=Cc2cc(-c3ccc(N4CCOCC4)cc3)ccc2SCC1
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: C1CCOC1
Solvent: CCO
Product: O=C(O)C1=Cc2cc(-c3ccc(N4CCOCC4)cc3)ccc2SCC1
Reaction time: 144 h
Yield: 94.8 %

Procedure:
To a solution of methyl 7-(4-morpholinophenyl)-2,3-dihydro-1-benzothiepine-4-carboxylate (0.55 g) in ethanol/THF (30/30 ml) was added at room temperature 1N sodium hydroxide solution (1.8 ml), and the mixture was stirred for 6 days and then refluxed for 2 hours. To the mixture was added 1N hydrochloric acid (1.8 ml). The resulting solid was collected by filtration, which was washed with ethanol and diethylether to give yellow powder of 7-(4-morpholinophenyl)-2,3-dihydro-l-benzo-thiepine-4-carboxylic acid (502.2 mg).
Reaction SMILES: [Cl:1][C:2]1[N:6]2[CH2:7][CH2:8][NH:9][CH2:10][C:5]2=[C:4]([C:11]([NH2:13])=[O:12])[C:3]=1[C:14]1[CH:19]=[CH:18][CH:17]=[C:16]([F:20])[CH:15]=1.[F:21][C:22]([F:40])([F:39])[C:23]([NH:26][C:27](=O)[O:28]C1C=CC([N+]([O-])=O)=CC=1)([CH3:25])[CH3:24].C(=O)([O-])[O-].[Na+].[Na+].[OH-].[Na+]>C(#N)C>[Cl:1][C:2]1[N:6]2[CH2:7][CH2:8][N:9]([C:27]([NH:26][C:23]([CH3:25])([CH3:24])[C:22]([F:40])([F:39])[F:21])=[O:28])[CH2:10][C:5]2=[C:4]([C:11]([NH2:13])=[O:12])[C:3]=1[C:14]1[CH:19]=[CH:18][CH:17]=[C:16]([F:20])[CH:15]=1
Reactant: NC(=O)c1c(-c2cccc(F)c2)c(Cl)n2c1CNCC2
Reactant: CC(C)(NC(=O)Oc1ccc([N+](=O)[O-])cc1)C(F)(F)F
Agent: O=C([O-])[O-]
Agent: [Na+]
Agent: [OH-]
Solvent: CC#N
Product: CC(C)(NC(=O)N1CCn2c(Cl)c(-c3cccc(F)c3)c(C(N)=O)c2C1)C(F)(F)F
Temperature: 65 °C

Procedure:
A suspension of 0.165 (0.56 mmol) of 6-chloro-7-(3-fluorophenyl)-1,2,3,4-tetrahydropyrrolo[1,2-a]pyrazine-8-carboxamide, 0.197 g (0.67 mmol) of 4-nitrophenyl 1,1,1-trifluoro-2-methylpropan-2-ylcarbamate and 0.155 (1.12 mmol) of sodium carbonate in 3 ml of acetonitrile is heated at 65° C. for 1 hour 30 minutes. After cooling, the mixture is poured into aqueous 1N sodium hydroxide solution and the product is extracted with dichloromethane. After drying over sodium sulfate and filtering, the solvent is evaporated off under reduced pressure and the residue is purified by chromatography on a column of 24 g of silica gel, eluting with a mixture of 3% methanol in dichloromethane, to give 0.125 g of 6-chloro-7-(3-fluorophenyl)-N2-(1,1,1-trifluoro-2-methylpropan-2-yl)-3,4-dihydropyrrolo[1,2-a]pyrazine-2,8(1H)-dicarboxamide in the form of a white powder after crystallization from 4 ml of acetonitrile, filtering off and drying under reduced pressure.
Reaction SMILES: [F:1][C:2]1[C:3](I)=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][C:6](=[O:11])/[C:5]/2=[CH:12]\[C:13]1[NH:14][CH:15]=[CH:16][CH:17]=1.C([O-])([O-])=O.[Na+].[Na+].[OH:25][C:26]1[CH:31]=[CH:30][C:29](B(O)O)=[CH:28][CH:27]=1>COCCOC.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>[F:1][C:2]1[C:3]([C:29]2[CH:30]=[CH:31][C:26]([OH:25])=[CH:27][CH:28]=2)=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][C:6](=[O:11])/[C:5]/2=[CH:12]\[C:13]1[NH:14][CH:15]=[CH:16][CH:17]=1
Reactant: O=C1Nc2ccc(F)c(I)c2/C1=C/c1ccc[nH]1
Reactant: OB(O)c1ccc(O)cc1
Agent: Cl[Pd](Cl)([P](c1ccccc1)(c1ccccc1)c1ccccc1)[P](c1ccccc1)(c1ccccc1)c1ccccc1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: COCCOC
Product: O=C1Nc2ccc(F)c(-c3ccc(O)cc3)c2/C1=C/c1ccc[nH]1

Procedure:
A solution of (Z)-1,3-dihydro-5-fluoro-4-iodo-3-[(1H-pyrrol-2-yl)methylene]-2H-indol-2-one (100 mg, 0.28 mmol) (Starting Material 12), 2M aqueous Na2CO3 solution (0.28 mL), (Ph3P)2PdCl2 (22.9 mg, 0.028 mmol) and 4-hydroxyphenylboronic acid (77.2 mg, 0.56 mmol) in 1,2-dimethoxyethane (10 mL) was heated at 104° C. for 2 days. The reaction mixture was filtered and concentrated. The crude material was purified by reverse phase HPLC to give (Z)-1,3-Dihydro-5-fluoro-4-(4-hydroxyphenyl)-3-[(1H-pyrrol-2-yl)methylene]-2H-indol-2-one. (Yield 55mg, 61%).
Reaction SMILES: C1(P(C2C=CC=CC=2)CCCCP(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[CH2:31]([O:33][C:34]([CH:36]1[CH2:41][CH2:40][N:39]([C:42](=[O:68])[C:43]2[CH:48]=[CH:47][CH:46]=[C:45]([C@@H:49]([N:57]3[CH2:62][C@@H:61]([CH3:63])[N:60](CC=C)[CH2:59][C@@H:58]3[CH3:67])[C:50]3[CH:55]=[CH:54][CH:53]=[C:52]([OH:56])[CH:51]=3)[CH:44]=2)[CH2:38][CH2:37]1)=[O:35])[CH3:32].C(O)(=O)C1C(=CC=CC=1)S>C1COCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[CH2:31]([O:33][C:34]([CH:36]1[CH2:41][CH2:40][N:39]([C:42](=[O:68])[C:43]2[CH:48]=[CH:47][CH:46]=[C:45]([C@@H:49]([N:57]3[CH2:62][C@@H:61]([CH3:63])[NH:60][CH2:59][C@@H:58]3[CH3:67])[C:50]3[CH:55]=[CH:54][CH:53]=[C:52]([OH:56])[CH:51]=3)[CH:44]=2)[CH2:38][CH2:37]1)=[O:35])[CH3:32]
Reactant: C=CCN1C[C@H](C)N([C@@H](c2cccc(O)c2)c2cccc(C(=O)N3CCC(C(=O)OCC)CC3)c2)C[C@H]1C
Agent: [Pd]
Agent: O=C(/C=C/c1ccccc1)/C=C/c1ccccc1
Agent: O=C(O)c1ccccc1S
Solvent: C1CCOC1
Product: CCOC(=O)C1CCN(C(=O)c2cccc([C@H](c3cccc(O)c3)N3C[C@@H](C)NC[C@@H]3C)c2)CC1
Temperature: 25 °C
Reaction time: 8 h
Yield: 90.3 %

Procedure:
Bis(dibenzylideneacetone)palladium (398 mg) was added to a solution of 1,4-bis(diphenylphosphino)butane (295 mg) in THF (7.3 mL) under nitrogen at room temperature for 10 minutes. The resulting Pd-catalyst was transferred to the solution of 1-{3-[(R)-((2S,5R)-4-allyl-2,5-dimethyl-piperazin-1-yl)-(3-hydroxy-phenyl)-methyl]-benzoyl}-piperidine-4-carboxylic acid ethyl ester (3.6 g, Ex. 58) and thiosalicylic acid (1.71 g) in THF (40 mL) via a syringe. The reaction was stirred under nitrogen at room temperature for overnight. The reaction mixture was concentrated under vacuum. EtOAc (75 mL) was added to the residue, followed by the addition of 1 N aqueous HCl (110 mL). The EtOAc layer and acidic water layer were separated. The acidic water layer was extracted with EtOAc (50 mL×2). The acidic water layer was neutralized with saturated NaHCO3 solution to pH≅8 and then extracted with n-butanol (75 mL×3). The combined n-butanol layer was washed with water (60 mL) and concentrated to give crude product, 1-{3-[(R)-((2S,5R)-2,5-dimethyl-piperazin-1-yl)-(3-hydroxy-phenyl)-methyl]-benzoyl}-piperidine-4-carboxylic acid ethyl ester (3.0 g). 1H NMR (300 MHz, CD3OD) δ 7.55-7.37 (m, 3H), 7.27 (m, 1H), 7.18 (dd, J=8.0, 8.0, 1H), 6.71 (m, 2H), 6.61 (s, 1H), 5.36 (s, 1H), 4.44 (m, 1H), 4.14 (q, J=7.0 Hz, 2H), 3.68 (m, 1H), 3.08 (m, 2H), 2.89 (m, 2H), 2.65 (m, 2H), 2.46 (m, 1H), 2.00 (m, 1H), 1.84 (m, 1H), 1.76-1.45 (m, 3H), 1.25 (t, J=7.0 Hz, 3H), 1.21 (d, J=6.0 Hz, 3H), 0.96 (d, J=6.5, 3H).
Reaction SMILES: Cl.[S:2]1[CH2:7][CH2:6][CH:5]([NH2:8])[CH2:4][CH2:3]1.C(N(CC)CC)C.[N+:16]([C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][C:20]=1[S:25](Cl)(=[O:27])=[O:26])([O-:18])=[O:17]>C1COCC1>[N+:16]([C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][C:20]=1[S:25]([NH:8][CH:5]1[CH2:6][CH2:7][S:2][CH2:3][CH2:4]1)(=[O:27])=[O:26])([O-:18])=[O:17]
Reactant: NC1CCSCC1
Reactant: O=[N+]([O-])c1ccccc1S(=O)(=O)Cl
Agent: Cl
Solvent: CCN(CC)CC
Solvent: C1CCOC1
Product: O=[N+]([O-])c1ccccc1S(=O)(=O)NC1CCSCC1
Temperature: 13 °C
Reaction time: 23 h
Yield: 92.5 %

Procedure:
To a suspension of tetrahydro-2H-thiopyran-4-amine hydrochloride (80.0 g) in THF (800 mL) were added triethylamine (239 mL) and 2-nitrobenzenesulfonyl chloride (126.9 g) under ice-cooling at an inside temperature of 2-24° C., and the mixture was stirred at room temperature for 23 hr. The reaction solution was partitioned and extracted with ethyl acetate and water, and the organic layer was washed with water and saturated brine, dried over magnesium sulfate, and concentrated under reduced pressure to the extent crystals do not precipitate and purified by silica gel column chromatography [eluent; hexane:ethyl acetate=50:50 (volume ratio)]. The obtained solid was washed with ethanol-diisopropyl ether (1:4), and dried under reduced pressure to give the title compound (145.6 g, yield 92%) as a pale-green solid.
Reaction SMILES: C1CCC(N=C=NC2CCCCC2)CC1.[C:16]([OH:20])(=O)[C:17]#[CH:18].[C:21]([C:24]1[CH:29]=[CH:28][C:27]([NH2:30])=[CH:26][CH:25]=1)#[C:22][CH3:23]>ClCCl>[C:21]([C:24]1[CH:29]=[CH:28][C:27]([NH:30][C:16](=[O:20])[C:17]#[CH:18])=[CH:26][CH:25]=1)#[C:22][CH3:23]
Reactant: C#CC(=O)O
Reactant: CC#Cc1ccc(N)cc1
Agent: C(=NC1CCCCC1)=NC1CCCCC1
Solvent: ClCCl
Product: C#CC(=O)Nc1ccc(C#CC)cc1
Reaction time: 0.5 h

Procedure:
1.2 g (5.86 mmol) of DCC is added to a solution of 375 mg (5.35 mmol) of propynoic acid in 10 mL of dichloromethane at 0° C. and the mixture is stirred for 30 minutes. Then 0.7 g (5.35 mmol) of 4-prop-1-ynylphenylamine dissolved in dichloromethane is slowly added dropwise and the mixture is stirred for 2 hours again at 0° C. The reaction mixture is then filtered through CELITE® filter aid and the filtrate is evaporated down. The purification is carried out by column chromatography on silica gel (eluant: dichloromethane/ethanol (40:1)). Yield: 0.7 g (71.4% of theory); C12H9NO (M=183.21); calc.: molecular ion peak (M+H)+: 184; found: molecular ion peak (M+H)+: 184; Rf value: 0.65 (silica gel, dichloromethane/ethanol/acetic acid 20:1).
Reaction SMILES: Br[C:2]1([Br:17])[CH2:4][C:3]1([C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1)[C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1.[CH2:18]([Li])CCC.CCCCCC.CI>O.C1COCC1>[Br:17][C:2]1([CH3:18])[CH2:4][C:3]1([C:5]1[CH:6]=[CH:7][CH:8]=[CH:9][CH:10]=1)[C:11]1[CH:12]=[CH:13][CH:14]=[CH:15][CH:16]=1
Reactant: [Li]CCCC
Reactant: BrC1(Br)CC1(c1ccccc1)c1ccccc1
Solvent: CCCCCC
Solvent: C1CCOC1
Solvent: CI
Product: CC1(Br)CC1(c1ccccc1)c1ccccc1
Temperature: -70 °C
Reaction time: 0.5 h
Yield: 89 %

Procedure:
Under a nitrogen atmosphere, 1,1-dibromo-2,2-diphenylcyclopropane(10.6 g, 30.0 mmol) obtained in Example 1-(1) and THF (tetrahydrofuran, 120 ml) were placed in a reaction flask and cooled to −70° C. To the mixture, n-butyllithium in hexane (20 ml, 1.57M, 31.4 mmol) was added gradually, and the mixture was stirred at the same temperature for 30 minutes. Methyl iodide (2.1 ml, 33 mmol) was added to the reaction mixture and the resulting mixture was stirred for 30 minutes and then warmed to room temperature. Then, water was added to the reaction mixture and the organic layer was extracted with toluene. The toluene extract was dried over anhydrous magnesium sulfate and then the solvent was removed under reduced pressure. The residue was recrystallized from methanol to give the title compound (7.28 g, 89%) as white crystal.
Reaction SMILES: [C:1]([CH2:3][CH2:4][O:5][CH2:6][C:7]1[C:8]([N+:14]([O-])=O)=[C:9]([CH3:13])[CH:10]=[CH:11][CH:12]=1)#[N:2]>C(O)(=O)C.[Pt](=O)=O>[NH2:2][CH2:1][CH2:3][CH2:4][O:5][CH2:6][C:7]1[CH:12]=[CH:11][CH:10]=[C:9]([CH3:13])[C:8]=1[NH2:14]
Reactant: Cc1cccc(COCCC#N)c1[N+](=O)[O-]
Agent: O=[Pt]=O
Solvent: CC(=O)O
Product: Cc1cccc(COCCCN)c1N
Temperature: 25 °C
Reaction time: 6 h
Yield: 29.5 %

Procedure:
A solution of 12 g (55 mMol) of the nitro compound (2) in 140 ml of glacial acetic acid was combined with 550 mg of platinum dioxide (PtO2) and shaken at room temperature under a hydrogen atmosphere of 50 pounds per square inch (psi) for 6 hours. It was then filtered to remove the catalyst and the solvent was evaporated under reduced pressure. The residue was dissolved in 100 ml of n-butanol and the solution washed twice with 50 ml of saturated aqueous sodium bicarbonate solution. The aqueous washes were combined and extracted two 75 ml portions of n-butanol. The combined butanol extracts were combined, dried over anhydrous sodium sulfate (Na2SO4), and evaporated. The oily residue was purified on a preparative liquid chromatograph using silica gel as the adsorbent and eluting with 40:10:1 (v/v/v) chloroform (CHCl3):methanol:conc. ammonium hydroxide. This yielded 3.15 g (30% yield) of 2-(3-aminopropoxymethyl)-6-methylaniline (3) as an oil.
Reaction SMILES: Br[CH2:2][C:3]([C:5]1[CH:10]=[CH:9][C:8]([Cl:11])=[CH:7][CH:6]=1)=[CH2:4].[Cl:12][C:13]1[CH:14]=[C:15]([OH:21])[C:16](=[CH:19][CH:20]=1)[CH:17]=[O:18].C(=O)([O-])[O-].[K+].[K+].CN(C=O)C>O>[Cl:12][C:13]1[CH:20]=[CH:19][C:16]([CH:17]=[O:18])=[C:15]([O:21][CH2:2][C:3]([C:5]2[CH:10]=[CH:9][C:8]([Cl:11])=[CH:7][CH:6]=2)=[CH2:4])[CH:14]=1
Reactant: O=Cc1ccc(Cl)cc1O
Reactant: C=C(CBr)c1ccc(Cl)cc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CN(C)C=O
Product: C=C(COc1cc(Cl)ccc1C=O)c1ccc(Cl)cc1
Temperature: 25 °C
Reaction time: 72 h
Yield: 106.8 %

Procedure:
A mixture of 19.2 g (0.083 mol) of the product from Step A, 10.0 g (0.064 mol) of 4-chlorosalicylaldehyde, 17.6 g (0.13 mol) of potassium carbonate and 64 mL of DMF was stirred at RT for 72 h. Resulting mixture treated with 125 mL of H2O and filtered. Solids were washed with several portions of H2O and dried in a vacuum oven at 40° C. to give 21.0 g of a brown solid. 1H NMR (CDCl3, 200 MHz) δ4.99 (s, 2H), 5.51 (s, 1H), 5.65 (s, 1H), 7.04-7.07 (m, 2H), 7.25-7.45 (m, 4H), 7.77 (d, 1H), 10.28 (s, 1H).
Reaction SMILES: C[O-].[Na+].[NH2:4][C:5]1[CH:15]=[CH:14][C:8]([C:9]([O:11][CH2:12][CH3:13])=[O:10])=[CH:7][CH:6]=1.[CH3:16][C:17](=[CH:19][CH2:20][CH2:21][CH:22](CCO)[CH3:23])[CH3:18].CCO>C1CCCCC1>[NH2:4][C:5]1[CH:6]=[CH:7][C:8]([C:9]([O:11][CH2:12][CH2:13][CH:22]([CH3:23])[CH2:21][CH2:20][CH:19]=[C:17]([CH3:18])[CH3:16])=[O:10])=[CH:14][CH:15]=1
Reactant: CCOC(=O)c1ccc(N)cc1
Reactant: CC(C)=CCCC(C)CCO
Agent: C[O-]
Agent: [Na+]
Solvent: C1CCCCC1
Solvent: CCO
Product: CC(C)=CCCC(C)CCOC(=O)c1ccc(N)cc1
Yield: 30.3 %

Procedure:
Sodium methoxide (2.5 g, cat.) was added to a suspension of ethyl 4-aminobenzoate (10 g, 60 mmol), citronellol (15 g, 90 mmol) in cyclohexane (100 mL). The suspension was heated under reflux for 8 hours with the azeotropic removal of EtOH. The mixture was cooled and filtered through a plug of silica (400 mL) with cyclohexane:isopropanol (95:5) as eluant to give the ester (5.0 g, 30%)as a pale yellow solid.
Reaction SMILES: [CH2:1]([O:3][CH:4]([O:35][CH2:36][CH3:37])[C:5]1[CH:34]=[CH:33][C:8]([CH2:9][C:10]([CH2:19][C:20]2[CH:25]=[CH:24][C:23]([CH:26]([O:30][CH2:31][CH3:32])[O:27][CH2:28][CH3:29])=[CH:22][CH:21]=2)([C:15](OC)=[O:16])[C:11](OC)=[O:12])=[CH:7][CH:6]=1)[CH3:2].[H-].[H-].[H-].[H-].[Li+].[Al+3]>C1COCC1>[CH2:36]([O:35][CH:4]([O:3][CH2:1][CH3:2])[C:5]1[CH:34]=[CH:33][C:8]([CH2:9][C:10]([CH2:19][C:20]2[CH:21]=[CH:22][C:23]([CH:26]([O:27][CH2:28][CH3:29])[O:30][CH2:31][CH3:32])=[CH:24][CH:25]=2)([CH2:11][OH:12])[CH2:15][OH:16])=[CH:7][CH:6]=1)[CH3:37]
Reactant: CCOC(OCC)c1ccc(CC(Cc2ccc(C(OCC)OCC)cc2)(C(=O)OC)C(=O)OC)cc1
Agent: [Al+3]
Agent: [H-]
Agent: [Li+]
Solvent: C1CCOC1
Product: CCOC(OCC)c1ccc(CC(CO)(CO)Cc2ccc(C(OCC)OCC)cc2)cc1
Temperature: 25 °C
Reaction time: 0.5 h

Procedure:
To a solution of dimethyl 2,2-di[4-(diethoxymethyl)benzyl]malonate (3 g, crude) in 200 mL of THF coole at 0° C. was added of LiAlH4 (0.7 g). The mixture was stirred for 0.5 h at room temperature and the quenched with acetone (5 mL), followed by 100 mL of 20% aqeous sodium potassium tartrate solution. The mixture was extracted with 2×200 mL of EtOAc. The extract was dried over Na2SO4 and concentrated to give the crude title compound which was used for next step without further purification.
Reaction SMILES: P(Cl)(Cl)(Cl)=O.CN(C)[CH:8]=[O:9].[C:11]([C:15]1[O:16][CH:17]=[CH:18][CH:19]=1)([CH3:14])([CH3:13])[CH3:12].C(=O)([O-])[O-].[Na+].[Na+]>>[C:11]([C:15]1[O:16][C:17]([CH:8]=[O:9])=[CH:18][CH:19]=1)([CH3:14])([CH3:13])[CH3:12]
Reactant: CN(C)C=O
Reactant: CC(C)(C)c1ccco1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: O=P(Cl)(Cl)Cl
Product: CC(C)(C)c1ccc(C=O)o1
Temperature: 10 °C
Reaction time: 3 h
Yield: 99 %

Procedure:
Phosphorus oxychloride (26.75 g, 0.174 mol) was added dropwise to dimethylformamide (12.92 g, 0.177 mol). This mixture was cooled to 10° C. for 1/2 hour, then 2-t-butylfuran (18.45 g, 0.149 mol) was added dropwise and the mixture stirred at room temperature for 3 hours. The mixture was poured into ice/water, neutralised with sodium carbonate and extracted into diethyl ether. The ethereal extracts were washed with water, dried over anhydrous sodium sulphate and the solvent removed to give a brown oil. Purification by column chromatography (silica eluted with petroleum ether/ethyl acetate 9:1) gave 5-t-butyl-2-furancarboxaldehyde (22.46 g, 99%).
Reaction SMILES: [C:1]([CH2:4][CH2:5][CH2:6][C:7]([O:9][CH2:10][CH3:11])=[O:8])(=O)[CH3:2].[CH3:12][N:13]([CH3:15])[NH2:14].FC(F)(F)C(O)=O>C1(C)C=CC=CC=1>[CH3:12][N:13]([N:14]=[C:1]([CH3:2])[CH2:4][CH2:5][CH2:6][C:7]([O:9][CH2:10][CH3:11])=[O:8])[CH3:15]
Reactant: CCOC(=O)CCCC(C)=O
Reactant: CN(C)N
Solvent: Cc1ccccc1
Solvent: O=C(O)C(F)(F)F
Product: CCOC(=O)CCCC(C)=NN(C)C
Yield: 61.4 %

Procedure:
15.8 g (100 mmol) of ethyl 4-acetyl-butanoate and 6 g (100 mmol) of anhydrous N,N-dimethyl hydrazine in 50 ml of toluene containing 0.1 ml of trifluoroacetic acid were heated at 70° C. for 5 hours. The mixture was then washed 20 with water, dried over anhydrous sodium sulfate and evaporated to give 12.3 g (79% yield) of the title compound.
Reaction SMILES: C([NH:8][S:9]([C:12]1[C:20]2[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=2)[NH:14][CH:13]=1)(=[O:11])=[O:10])(OC(C)(C)C)=O.[Na+].[I-].C[Si](Cl)(C)C.O>CC#N>[NH:14]1[C:15]2[C:20](=[CH:19][CH:18]=[CH:17][CH:16]=2)[C:12]([S:9]([NH2:8])(=[O:11])=[O:10])=[CH:13]1
Reactant: CC(C)(C)OC(=O)NS(=O)(=O)c1c[nH]c2ccccc12
Agent: C[Si](C)(C)Cl
Agent: [I-]
Agent: [Na+]
Solvent: O
Solvent: CC#N
Product: NS(=O)(=O)c1c[nH]c2ccccc12
Temperature: 0 °C
Reaction time: 0.25 h
Yield: 97.3 %

Procedure:
N-Boc 1H-indole-3-sulfonamide (1.47 g, 4.96 mmol) was dissolved in CH3CN (75 mL), and NaI (3.72 g, 24.80 mmol) added. The mixture was cooled to 0° C. under N2, and tri-methylsilyl chloride (TMS-Cl, 2.69 g, 24.80 mmol) added dropwise, the mixture stirred for 15 min at 0° C., then stirred at RT overnight. The mixture was poured into water, the resulting off-white precipitate filtered, washed with water and hexane, and air dried to provide 1H-indole-3-sulfonic acid amide (947 mg, 97% yield), which was used without further purification.