Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][O:2][C:3]([C:5]1[CH:10]=[CH:9][C:8](Cl)=[CH:7][N:6]=1)=[O:4].[F:12][C:13]([F:20])([F:19])[C:14]1[CH:18]=[CH:17][NH:16][N:15]=1.C([O-])([O-])=O.[K+].[K+]>CN(C=O)C>[CH3:1][O:2][C:3]([C:5]1[CH:10]=[CH:9][C:8]([N:16]2[CH:17]=[CH:18][C:14]([C:13]([F:20])([F:19])[F:12])=[N:15]2)=[CH:7][N:6]=1)=[O:4]
Reactant: FC(F)(F)c1cc[nH]n1
Reactant: COC(=O)c1ccc(Cl)cn1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: COC(=O)c1ccc(-n2ccc(C(F)(F)F)n2)cn1
Temperature: 105 °C
Yield: 3.2 %

Procedure:
A mixture of 5-chloro-pyridine-2-carboxylic acid methyl ester (1.37 g), 3-trifluoromethyl-1H-pyrazole (1.63 g) and powdered K2CO3 (1.67 g) in DMF (20 ml) was heated to 105° C. for 20 h. The mixture was evaporated and the residue partitioned between water and dichloromethane, the organic layer was washed with water, dried and evaporated. The residue was chromatographed on silica using n-heptane/ethyl acetate (gradient from 3:1 to 1:1) to give 5-(3-trifluoromethyl-pyrazol-1-yl)-pyridine-2-carboxylic acid methyl ester (70 mg) as a colorless solid. MS (ESI): m/z=272.1 [ M+H]+.
Reaction SMILES: Cl.CN(C)CCCN=C=NCC.[CH2:13]([C:16]1[C:23]([F:24])=[C:22]([F:25])[C:19]([CH2:20][OH:21])=[C:18]([F:26])[C:17]=1[F:27])[CH:14]=[CH2:15].[C:28]([C:30]([CH3:40])=[CH:31][C@@H:32]1[C@@H:34]([C:35](O)=[O:36])[C:33]1([CH3:39])[CH3:38])#[N:29]>CN(C)C1C=CN=CC=1.C(Cl)(Cl)Cl>[C:28]([C:30]([CH3:40])=[CH:31][C@@H:32]1[C@@H:34]([C:35]([O:21][CH2:20][C:19]2[C:18]([F:26])=[C:17]([F:27])[C:16]([CH2:13][CH:14]=[CH2:15])=[C:23]([F:24])[C:22]=2[F:25])=[O:36])[C:33]1([CH3:39])[CH3:38])#[N:29]
Reactant: C=CCc1c(F)c(F)c(CO)c(F)c1F
Reactant: CC(C#N)=C[C@@H]1[C@@H](C(=O)O)C1(C)C
Agent: CCN=C=NCCCN(C)C
Agent: CN(C)c1ccncc1
Agent: Cl
Solvent: ClC(Cl)Cl
Product: C=CCc1c(F)c(F)c(COC(=O)[C@@H]2[C@@H](C=C(C)C#N)C2(C)C)c(F)c1F
Temperature: 25 °C
Reaction time: 3 h
Yield: 94 %

Procedure:
Under a nitrogen atmosphere, 0.23 g of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride was added to a mixture of 0.20 g of 4-allyl-2,3,5,6-tetrafluorobenzyl alcohol, 0.16 g of (1R)-trans-3-(2-cyano-1-propeny)-2,2-dimethylcyclopropanecarboxylic acid, 0.05 g of 4-dimethylaminopyridine and 4 ml of anhydrous chloroform, and the mixture was stirred at room temperature for 3 hours. Thereafter, the reaction mixture was poured into ice water, followed by extraction with ethyl acetate two times. Ethyl acetate layers were combined, washed with an aqueous saturated sodium chloride solution, dried with anhydrous sodium sulfate, and concentrated under reduced pressure. The resulting residue was subjected to silica gel column chromatography to obtain 0.32 g of 4-allyl-2,3,5,6-tetrafluorobenzyl (1R)-trans-3-(2-cyano-1-propenyl)-2,2-dimethylcyclopropanecarboxylate represented by the following formula:
Reaction SMILES: [C:1]([CH2:3][CH2:4][CH2:5][NH:6][C:7]1([CH3:17])[CH2:12][C:11]([CH3:14])([CH3:13])[CH2:10][C:9]([CH3:16])([CH3:15])[CH2:8]1)#N.[ClH:18]>C(O)C.[Pd]>[ClH:18].[CH3:17][C:7]1([N:6]2[CH2:5][CH2:4][CH2:3][CH2:1]2)[CH2:12][C:11]([CH3:14])([CH3:13])[CH2:10][C:9]([CH3:16])([CH3:15])[CH2:8]1
Reactant: CC1(C)CC(C)(C)CC(C)(NCCCC#N)C1
Agent: [Pd]
Agent: Cl
Solvent: CCO
Product: CC1(C)CC(C)(C)CC(C)(N2CCCC2)C1
Yield: 49 %

Procedure:
N-(3-Cyanopropyl)-1,3,3,5,5-pentamethylcyclohexylamine (2) (1.2 g, 5.1 mmol) in ethanol (120 ml) and conc. HCl (4 ml) was hydrogenated over 10% Pd/C (250 mg) at 7 bar for 40 h (after 24 h additional portion of catalyst (260 mg) was added). The catalyst was removed by filtration through celite pad and solvent evaporated. The residue was treated with acetonitrile, the solids filtered off and the filtrate evaporated. The crude product vas crystallized from ether to give N-(1,3,3,5,5-pentamethylcyclohexyl) pyrrolidine hydrochloride (3) (0.67 g, 49%) with m.p. 156-158° C.
Reaction SMILES: [OH:1][C:2]1[CH:10]=[CH:9][CH:8]=[C:7]([CH3:11])[C:3]=1[C:4]([OH:6])=[O:5].[Br:12]N1C(=O)CCC1=O.S(=O)(=O)(O)[O-].[Na+]>C(#N)C>[Br:12][C:8]1[C:7]([CH3:11])=[C:3]([C:2]([OH:1])=[CH:10][CH:9]=1)[C:4]([OH:6])=[O:5]
Reactant: O=C1CCC(=O)N1Br
Reactant: Cc1cccc(O)c1C(=O)O
Agent: O=S(=O)([O-])O
Agent: [Na+]
Solvent: CC#N
Product: Cc1c(Br)ccc(O)c1C(=O)O
Temperature: 0 °C
Reaction time: 1 h
Yield: 79.8 %

Procedure:
Step 2 A suspension of 2-hydroxy-6-methylbenzoic acid (1.32 g, 8.68 mmol) in acetonitrile (20 mL) at −20° C. was treated with tetrafluoroboric acid dimethyl ether complex (1.109 mL, 9.11 mmol), followed by portionwise addition of N-bromosuccinimide (1.699 g, 9.54 mmol) over 30 min. The mixture was warmed to 0° C. and stirred for 1 h, then was treated with 40% aqueous sodium bisulfate (10 mL). The acetonitrile was removed under vacuum and the aqueous residue was extracted with EtOAc (3×40 mL). The combined organic layers were washed with water and brine, dried and concentrated to give 3-bromo-6-hydroxy-2-methylbenzoic acid as a white solid (1.60 g, 80%). 1H NMR (400 MHz, methanol-d4) δ 7.47 (1H, d, J=8.80 Hz), 6.67 (1H, d, J=8.80 Hz), 2.50 (3H, s). Mass spectrum m/z 231, 233 (M-1-1)−.
Reaction SMILES: [C:1]([NH:5][C:6]([C:8]1[C:16]2[C:11](=[N:12][CH:13]=[C:14]([N:17]3[C:25]4[C:20](=[CH:21][C:22]([C:26]([F:29])([F:28])[F:27])=[CH:23][CH:24]=4)[CH:19]=[N:18]3)[N:15]=2)[N:10](COCC[Si](C)(C)C)[CH:9]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].FC(F)(F)C(O)=O>ClCCl>[C:1]([NH:5][C:6]([C:8]1[C:16]2[C:11](=[N:12][CH:13]=[C:14]([N:17]3[C:25]4[C:20](=[CH:21][C:22]([C:26]([F:27])([F:29])[F:28])=[CH:23][CH:24]=4)[CH:19]=[N:18]3)[N:15]=2)[NH:10][CH:9]=1)=[O:7])([CH3:4])([CH3:2])[CH3:3]
Reactant: CC(C)(C)NC(=O)c1cn(COCC[Si](C)(C)C)c2ncc(-n3ncc4cc(C(F)(F)F)ccc43)nc12
Solvent: ClCCl
Solvent: O=C(O)C(F)(F)F
Product: CC(C)(C)NC(=O)c1c[nH]c2ncc(-n3ncc4cc(C(F)(F)F)ccc43)nc12
Reaction time: 15 h
Yield: 7.2 %

Procedure:
To a stirred solution of N-tert-butyl-2-(5-(trifluoromethyl)-1H-indazol-1-yl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide (110 mg, 207 μmol) in dichloromethane (3 mL) was added trifluoroacetic acid (1 mL). After 15 h, the mixture was concentrated in vacuo, add 25 mL Jan. 10, 1960 mixture of ammonium hydroxide/methanol/dichloromethane, stir for 1 hour. concentrated in vacuo. Purification by chromatography (silica, 24 g Analogix column, 0-4% methanol containing 10% ammonium hydroxide in dichloromethane) gave 2-(5-trifluoromethyl-indazol-1-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid tert-butylamide (6 mg, 7%). MS (M−H)−=401; 1H NMR (DMSO-d6) δ: 9.04 (s, 1H), 8.74 (d, J=9.0 Hz, 1H), 8.54 (d, J=2.8 Hz, 1H), 8.46 (s, 1H), 8.39 (d, J=2.5 Hz, 1H), 8.33 (s, 1H), 8.09 (s, 1H), 1.50 (s, 4H), 1.44 (s, 9H).
Reaction SMILES: C(N(CC)CC)C.[N+:8]([C:11]1[CH:25]=[CH:24][C:14]([CH2:15][O:16][C:17]([NH:19][CH2:20][C:21]([OH:23])=[O:22])=[O:18])=[CH:13][CH:12]=1)([O-:10])=[O:9].ClC(OCC)=O.O[C:33]1[CH:41]=[CH:40][C:36]([C:37]([OH:39])=[O:38])=[CH:35][CH:34]=1>ClCCl>[N+:8]([C:11]1[CH:12]=[CH:13][C:14]([CH2:15][O:16][C:17]([NH:19][CH2:20][C:21]([O:23][C:33]2[CH:41]=[CH:40][C:36]([C:37]([OH:39])=[O:38])=[CH:35][CH:34]=2)=[O:22])=[O:18])=[CH:24][CH:25]=1)([O-:10])=[O:9]
Reactant: O=C(O)c1ccc(O)cc1
Reactant: O=C(O)CNC(=O)OCc1ccc([N+](=O)[O-])cc1
Agent: CCOC(=O)Cl
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: O=C(CNC(=O)OCc1ccc([N+](=O)[O-])cc1)Oc1ccc(C(=O)O)cc1
Reaction time: 0.33 h

Procedure:
Triethylamine (4 ml) was added to a suspension of N-(4-nitrobenzyloxycarbonyl)glycine (7.25 g) in dry dichloromethane at -20° C. Ethyl chloroformate (2.75 ml) was added to the resultant solution and the mixture stirred at -20° to -10° C. for 20 mins. A solution of 4-hydroxybenzoic acid (3.94 g) and triethylamine (4 ml) in dichloromethane (50 ml) was added dropwise, and stirring continued for 2.5 h after addition. The mixture was filtered, the filtrate washed with 10% aqueous citric acid (20 ml), water (20 ml), and brine (20 ml), and dried (MgSO4). Evaporation under reduced pressure afforded the crude product, 4-[N-(4-nitrobenzyloxycarbonyl)glycyloxy]benzoic acid as a pale yellow foam. Without further purification, 4-[N-(4-nitrobenzyloxycarbonyl)glycyloxy]benzoic acid was treated with chloromethylchlorosulphate (5.77 g) under the conditions described in Example 55b. After work-up and chromatography as described therein, the title compound was obtained as a white crystalline solid (1.81 g), m.p. 119°-120° C. (ethylacetate/hexane); νmax (CH2Cl2) 3450, 1780, 1740, 1610, and 1520 cm-1 ; δH (CDCl3) 4.33 (2H, d, J 6 Hz), 5.33 (2H, s), 5.72 (1H, br t, J 6 Hz), 6.03 (2H, s), 7.23-7.70 (4H, m), and 8.18-8.40 (4H, m).
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]2[C:10]3([CH2:14][CH2:13][N:12]([C:15]([C@@H:17]4[CH2:21][O:20]C(C)(C)[O:18]4)=[O:16])[CH2:11]3)[CH2:9][N:8]([C:24]([NH:26][C:27]3[S:28][C:29]([Cl:32])=[CH:30][N:31]=3)=[O:25])[C:5]2=[CH:6][CH:7]=1.CO.Cl>O1CCCC1.O>[Cl:1][C:2]1[CH:3]=[C:4]2[C:10]3([CH2:14][CH2:13][N:12]([C:15](=[O:16])[C@@H:17]([OH:18])[CH2:21][OH:20])[CH2:11]3)[CH2:9][N:8]([C:24]([NH:26][C:27]3[S:28][C:29]([Cl:32])=[CH:30][N:31]=3)=[O:25])[C:5]2=[CH:6][CH:7]=1
Reactant: CC1(C)OC[C@@H](C(=O)N2CCC3(C2)CN(C(=O)Nc2ncc(Cl)s2)c2ccc(Cl)cc23)O1
Agent: Cl
Solvent: C1CCOC1
Solvent: CO
Solvent: O
Product: O=C([C@@H](O)CO)N1CCC2(C1)CN(C(=O)Nc1ncc(Cl)s1)c1ccc(Cl)cc12
Temperature: 50 °C
Reaction time: 0.33 h
Yield: 40.7 %

Procedure:
5-Chloro-N-(5-chlorothiazol-2-yl)-1′-((S)-2,2-dimethyl-1,3-dioxolane-4-carbonyl)spiro[indoline-3,3′-pyrrolidine]-1-carboxamide (116 mg, 0.233 mmol) was dissolved in tetrahydrofuran (1 mL) and methanol (1 mL) Thereafter, a 1 N aqueous solution of hydrochloric acid (1 mL) was added to the above obtained solution at room temperature, and the thus obtained mixture was then stirred at 50° C. for 20 minutes. Thereafter, the reaction solution was diluted with water, and was then extracted with chloroform. The organic layer was washed with brine, and was then dried over anhydrous sodium sulfate, followed by concentration in vacuo. The obtained residue was purified by silica gel column chromatography (chloroform:methanol=10:1) to obtain the captioned compound (43.4 mg, 41%) in the form of a colorless amorphous product.
Reaction SMILES: [NH2:1][C:2]1[C:3]([C:18](O)=[O:19])=[N:4][C:5]([C:12]2[CH:13]=[N:14][N:15]([CH3:17])[CH:16]=2)=[C:6]([C:8]([F:11])([F:10])[F:9])[CH:7]=1.[NH2:21][CH2:22][C:23]([CH3:29])([OH:28])[C:24]([F:27])([F:26])[F:25]>>[NH2:1][C:2]1[C:3]([C:18]([NH:21][CH2:22][C:23]([OH:28])([CH3:29])[C:24]([F:27])([F:26])[F:25])=[O:19])=[N:4][C:5]([C:12]2[CH:13]=[N:14][N:15]([CH3:17])[CH:16]=2)=[C:6]([C:8]([F:10])([F:11])[F:9])[CH:7]=1
Reactant: Cn1cc(-c2nc(C(=O)O)c(N)cc2C(F)(F)F)cn1
Reactant: CC(O)(CN)C(F)(F)F
Product: Cn1cc(-c2nc(C(=O)NCC(C)(O)C(F)(F)F)c(N)cc2C(F)(F)F)cn1

Procedure:
The title compound was prepared from 3-amino-6-(1-methyl-1H-pyrazol-4-yl)-5-(trifluoro methyl)picolinic acid and 3-amino-1,1,1-trifluoro-2-methylpropan-2-ol analogously to Example 4 1H NMR (400 MHz, Methanol-d4) δ 7.97 (1H, s), 7.85 (1H, s), 7.60 (1H, s), 3.97 (3H, s), 3.77 (1H, m), 3.56 (1H, m), 1.37 (3H, s)
Reaction SMILES: [CH3:1][N:2]([C:7]1[CH:12]=[CH:11][N:10]=[CH:9][CH:8]=1)[CH2:3][CH2:4][NH:5][CH3:6].F[C:14]1[CH:19]=[CH:18][C:17]([N+:20]([O-:22])=[O:21])=[CH:16][CH:15]=1.C(=O)(O)[O-].[Na+]>CN(C)C=O>[CH3:6][N:5]([C:14]1[CH:19]=[CH:18][C:17]([N+:20]([O-:22])=[O:21])=[CH:16][CH:15]=1)[CH2:4][CH2:3][N:2]([CH3:1])[C:7]1[CH:12]=[CH:11][N:10]=[CH:9][CH:8]=1
Reactant: O=[N+]([O-])c1ccc(F)cc1
Reactant: CNCCN(C)c1ccncc1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CN(C)C=O
Product: CN(CCN(C)c1ccc([N+](=O)[O-])cc1)c1ccncc1
Reaction time: 0.5 h

Procedure:
A mixture of the product of part (i) (0.83 g), 4-fluoronitrobenzene (0.71 g) and sodium bicarbonate (1.0 g) in N,N-dimethylformamide (20 ml ) was heated at 100° with stirring for 0.5 hour and then evaporated. The residue was stirred with water (2 ml) and the insoluble material was filtered off, washed with water and dried. The solid was chromatographed on silica gel. Elution with ethyl acetate/methanol (10:1) gave, after combination and evaporation of appropriate fractions, pure product (0.60 g), m.p. 126°-127° (from ethyl acetate/hexane).
Reaction SMILES: [C:1]1([C:3](=[CH:5][CH:6]=[CH:7][CH:8]=1)[OH:4])[OH:2].[OH2:9].S(=O)(=O)(O)O>[O-2].[O-2].[O-2].[Fe+2].[Fe+2].C(#N)C>[OH:2][C:1]1[C:3]([OH:4])=[CH:5][C:6]2[C:3]3[C:1](=[CH:8][C:7]([OH:9])=[C:6]([OH:9])[CH:5]=3)[C:7]3[C:6](=[CH:5][C:3]([OH:4])=[C:1]([OH:2])[CH:8]=3)[C:7]=2[CH:8]=1
Reactant: Oc1ccccc1O
Reactant: O
Agent: [Fe+2]
Agent: O=S(=O)(O)O
Agent: [O-2]
Solvent: CC#N
Product: Oc1cc2c3cc(O)c(O)cc3c3cc(O)c(O)cc3c2cc1O
Temperature: 30 °C
Yield: 45.5 %

Procedure:
Catechol (22.0 g, 0.2 moles) and diiron trioxide (ferric oxide) (31.9 g, 0.2 moles) were added into water (110 mL), and 98% sulfuric acid (440 g, 4.4 moles) was added dropwise to the solution while temperature of the solution was maintained at 30° C. or lower, to adjust the concentration in percent by weight of sulfuric acid in the reaction system at 80%. The solution was reacted at 30° C. for 6 hours with stirring. After completion of the reaction, water (500 mL) was added dropwise to the reaction solution, and the reaction solution was stirred for another 30 minutes. The resultant precipitate was collected by filtration, and the obtained crude crystal was washed with water and dried to give crude crystal (19.2 g). After a part of the crude crystal (5.0 g among 19.2 g) was dispersed in a mixed solvent of water (50 mL) and acetonitrile (200 mL), the dispersion liquid was heated up and stirred for 1 hour. After that, this dispersion liquid was filtered in hot state to filter off insoluble matter, the filtrate was then concentrated under reduced pressure, and the precipitated crystal was collected by filtration, and then dried, to give 2,3,6,7,10,11-hexahydroxytriphenylene (2.56 g, theoretical yield from catechol: 45.5%) in black powder form. 1H-NMR data of the obtained 2,3,6,7,10,11-hexahydroxytriphenylene measured were in accordance with those of 2,3,6,7,10,11-hexahydroxytriphenylene described in the reference. Also, the measurement results of 1H-NMR are shown below. In addition, content of iron ion in the obtained crystal was measured by inductively-coupled plasma optical emission spectroscopy (ICP-OES), and was found that content of iron ion (reduced quantity from metal iron) in the obtained 2,3,6,7,10,11-hexahydroxytriphenylene (2.56 g) was 0.087 mg (0.034 mg/g). Also, the measurement of iron ion content by inductively-coupled plasma optical emission spectroscopy was carried out using inductively-coupled plasma optical emission spectrometer SPS 3100 (manufactured by SII Nanotechnology Inc.) as follows. Several samples containing appropriate amount of metal iron dissolved in n-methyl-2-pyrrolidone were measured and a calibration curve was obtained based on the measurement results, in advance. Content of iron ion in 2,3,6,7,10,11-hexahydroxytriphenylene was obtained from the calibration curve.
Reaction SMILES: [C:1]1([C:7]2[N:8]=[CH:9][N:10]([CH2:18][O:19][CH2:20][CH2:21][Si:22]([CH3:25])([CH3:24])[CH3:23])[C:11]=2[C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[Li]CCCC.CN([CH:34]=[O:35])C>>[C:1]1([C:7]2[N:8]=[C:9]([CH:34]=[O:35])[N:10]([CH2:18][O:19][CH2:20][CH2:21][Si:22]([CH3:25])([CH3:24])[CH3:23])[C:11]=2[C:12]2[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=2)[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1
Reactant: CN(C)C=O
Reactant: C[Si](C)(C)CCOCn1cnc(-c2ccccc2)c1-c1ccccc1
Agent: [Li]CCCC
Product: C[Si](C)(C)CCOCn1c(C=O)nc(-c2ccccc2)c1-c1ccccc1
Yield: 78 %

Procedure:
Reaction of 4,5-diphenyl-1-(2-trimethylsilanyl-ethoxymethyl)-1H-imidazole (304 mg, 0.87 mmol), 2.5 M n-BuLi (452 uL, 1.13 mmol), and DMF (269 uL, 3.48 mmol) for 1 h at −40° C. gave the title compound (257 mg, 78%) as a yellow solid. 1H NMR (300 MHz, CDCl3) δ 0.00 (s, 9H), 0.89 (t, 2H, J=9.0 Hz), 3.58 (t, 2H, J=7.5 Hz), 5.61 (s, 2H), 7.26 (br s, 5H), 7.47 (br s, 5H), 9.95 (s, 1H).
Reaction SMILES: CN(C)[CH:3]1[C:14]2[C:6](=[CH:7][CH:8]=[C:9]3[C:13]=2[S:12](=C)[CH:11]=[N:10]3)[NH:5][C:4]1=[O:16].[CH3:18][CH2:19][C:20]1([C:28]2[CH:33]=[CH:32][C:31]([NH2:34])=[CH:30][CH:29]=2)[C:26](=[O:27])[NH:25][C:23](=[O:24])[CH2:22][CH2:21]1.[CH2:35](O)C>C(OCC)C>[CH2:19]([C:20]1([C:28]2[CH:29]=[CH:30][C:31]([NH:34]/[CH:35]=[C:3]3\[C:4](=[O:16])[NH:5][C:6]4[C:14]\3=[C:13]3[S:12][CH:11]=[N:10][C:9]3=[CH:8][CH:7]=4)=[CH:32][CH:33]=2)[CH2:21][CH2:22][C:23](=[O:24])[NH:25][C:26]1=[O:27])[CH3:18]
Reactant: CCC1(c2ccc(N)cc2)CCC(=O)NC1=O
Reactant: C=S1C=Nc2ccc3c(c21)C(N(C)C)C(=O)N3
Reactant: CCO
Solvent: CCOCC
Product: CCC1(c2ccc(N/C=C3\C(=O)Nc4ccc5ncsc5c43)cc2)CCC(=O)NC1=O
Temperature: 90 °C
Reaction time: 16 h
Yield: 54 %

Procedure:
A mixture of 8-dimethylamino-methylene-6,8-dihydro-1-thia-3,6-diaza-as-indacen-7-one (Procedure E, 0.040 g, 0.163 mmol), DL-aminoglutethimide (0.055 g, 0.237 mmol) in absolute ethanol (5 ml) was heated with stirring at 90° C. for 16 h. The reaction was diluted with ethanol and diethyl ether and the product collected by filtration to yield 0.038 g (54%) of the title compound.
Reaction SMILES: F[C:2]1[CH:9]=[C:8](F)[CH:7]=[CH:6][C:3]=1[CH:4]=[CH2:5].Cl[C:12](=[N:18][OH:19])[C:13]([O:15][CH2:16][CH3:17])=[O:14].C[CH2:21][O:22]CC.C(N(CC)CC)C>O>[CH3:21][O:22][C:2]1[CH:9]=[CH:8][CH:7]=[CH:6][C:3]=1[CH:4]1[O:19][N:18]=[C:12]([C:13]([O:15][CH2:16][CH3:17])=[O:14])[CH2:5]1
Reactant: CCOC(=O)C(Cl)=NO
Reactant: CCOCC
Reactant: C=Cc1ccc(F)cc1F
Solvent: CCN(CC)CC
Solvent: O
Product: CCOC(=O)C1=NOC(c2ccccc2OC)C1
Temperature: 0 °C
Reaction time: 3 h

Procedure:
4.2 g of 2,4-difluorostyrene and 4.55 g of ethyl 2-chloro-2-hydroximinoacetate are introduced into 350 ml of ether, and the mixture is cooled to 0° C. 3.03 g of triethylamine are added dropwise to this mixture at 0° C. The mixture is stirred for 3 hours at room temperature, 50 ml of water are then added, and the mixture is extracted using ether. After drying over MgSO4, the ether is distilled off, and the residue is purified over a silica column (eluent: n-heptane:ethyl acetate=8:2). This gave 6.68 g (86% of theory) of product of refractive index [n]D20 =1.5019.
Reaction SMILES: [CH2:1]([NH:9][C:10]1[C:11]([NH2:16])=[CH:12][CH:13]=[CH:14][CH:15]=1)[CH2:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.[Cl:17][CH2:18][C:19](O)=O>>[Cl:17][CH2:18][C:19]1[N:9]([CH2:1][CH2:2][C:3]2[CH:4]=[CH:5][CH:6]=[CH:7][CH:8]=2)[C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=2[N:16]=1
Reactant: O=C(O)CCl
Reactant: Nc1ccccc1NCCc1ccccc1
Product: ClCc1nc2ccccc2n1CCc1ccccc1
Yield: 61.6 %

Procedure:
The title compound was prepared in accordance with the general method of Example 191(C), from N1-phenethylbenzene-1,2-diamine (2.57 g, 12.11 mmol) and 2-chloroacetic acid (1.70 g, 18 mmol). The crude residue was purified over silicagel chromatography (prepacked 70 g silicagel column, Cyclohexane/AcOEt: from 80/20 to 70/30 as eluent) to afford 2.02 g of 2-(chloromethyl)-1-phenethyl-1H-benzo[d]imidazole (Yield: 61%) as a white crystalline solid.
Reaction SMILES: [CH3:1][CH2:2][CH2:3][CH2:4]C.[CH3:6][CH2:7][CH2:8][CH2:9][CH2:10][CH3:11]>CCCCCCC>[CH3:1][CH2:2][CH2:3][CH3:4].[CH3:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:1][CH3:2]
Reactant: CCCCCC
Reactant: CCCCC
Solvent: CCCCCCC
Product: CCCC
Product: CCCCCCCC

Procedure:
In this manner, butane, pentane, hexane, heptane and possibly octane would be formed. Thus, a methylene-alkane insertion chain reaction would be produced, to provide a high carbon chain hydrocarbon gas and/or liquid mixture 27.
Reaction SMILES: [CH2:1]([O:8][C:9]1[CH:10]=[C:11]([CH:19]=[CH:20][CH:21]=1)[NH:12][C:13](=[O:18])[CH2:14][C:15](=[O:17])[CH3:16])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH:22]([O-])([O-])[O:23]C.N1C2C(=CC=CC=2)C=C[CH:28]=1>CO>[CH2:1]([O:8][C:9]1[CH:10]=[C:11]([CH:19]=[CH:20][CH:21]=1)[NH:12][C:13](=[O:18])[CH2:14][C:15]([O:23][CH3:22])([O:17][CH3:28])[CH3:16])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: COC([O-])[O-]
Reactant: c1ccc2ncccc2c1
Reactant: CC(=O)CC(=O)Nc1cccc(OCc2ccccc2)c1
Solvent: CO
Product: COC(C)(CC(=O)Nc1cccc(OCc2ccccc2)c1)OC
Temperature: 20 °C
Reaction time: 16 h

Procedure:
A mixture of 70 g of m-benzyloxy-acetylacetanilide, 37 g of methyl orthoformate and 100 ml of methanol was stirred at 20°C. for 16 hours and 2 ml of quinoline were added thereto. The mixture was concentrated to dryness under reduced pressure and the residue was added to isopropyl ether. The mixture was cooled and vacuum filtered and the recovered precipitate was dried and chromatographed over silica gel. Elution with an 8-2 methylene chloride-acetone mixture gave 48 g of m-benzyloxy-3,3-dimethoxy-butyranilide melting at 83°C.
Reaction SMILES: [CH:1]([C:4]1[N:8]2[CH:9]=[C:10]([S:13][C:14]3[CH:21]=[CH:20][CH:19]=[CH:18][C:15]=3[CH2:16][NH2:17])[CH:11]=[CH:12][C:7]2=[N:6][N:5]=1)([CH3:3])[CH3:2].N1C=CC=CC=1.Cl[C:29]([O:31][C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1)=[O:30]>ClCCl>[C:32]1([O:31][C:29](=[O:30])[NH:17][CH2:16][C:15]2[CH:18]=[CH:19][CH:20]=[CH:21][C:14]=2[S:13][C:10]2[CH:11]=[CH:12][C:7]3[N:8]([C:4]([CH:1]([CH3:3])[CH3:2])=[N:5][N:6]=3)[CH:9]=2)[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1
Reactant: CC(C)c1nnc2ccc(Sc3ccccc3CN)cn12
Reactant: O=C(Cl)Oc1ccccc1
Solvent: ClCCl
Solvent: c1ccncc1
Product: CC(C)c1nnc2ccc(Sc3ccccc3CNC(=O)Oc3ccccc3)cn12
Reaction time: 0.33 h

Procedure:
To a solution of 2-(3-Isopropyl-[1,2,4]triazolo[4,3-a]pyridin-6-ylsulfanyl)-benzylamine (417 mg, 1.4 mmol) in dichloromethane (14 mL) at ambient temperature under nitrogen was added pyridine (226 μL, 2.8 mmol) and phenyl chloroformate (192 μL, 1.5 mmol). The reaction was stirred for 20 minutes, then quenched with saturated NaHCO3. The reaction mixture was extracted with dichloromethane, the combined organics washed with brine, dried over sodium sulfate, and concentrated in vacuo. Purification by flash chromatography (eluting with ethyl acetate), followed by ether/hexane trituration gave the above named compound as a white solid (526 mg, 90%).
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([CH:13]=[C:14]([Cl:16])[CH:15]=1)[CH2:5][N:6]1[CH:10]=[CH:9][N:8]=[C:7]1[CH:11]=O.[CH2:17]([NH2:24])[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1.[CH:25]1C=CC=CC=1>>[CH2:17]([NH:24][CH:11]([C:7]1[N:6]([CH2:5][C:4]2[CH:3]=[C:2]([Cl:1])[CH:15]=[C:14]([Cl:16])[CH:13]=2)[CH:10]=[CH:9][N:8]=1)[CH3:25])[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1
Reactant: O=Cc1nccn1Cc1cc(Cl)cc(Cl)c1
Reactant: c1ccccc1
Reactant: NCc1ccccc1
Product: CC(NCc1ccccc1)c1nccn1Cc1cc(Cl)cc(Cl)c1
Temperature: 0 °C
Reaction time: 1 h
Yield: 33 %

Procedure:
A mixture of 1-(3,5-dichloro-benzyl)-1H-imidazole-2-carbaldehyde (see Example 2) (128 mg, 0.50 mmol), benzylamine (64 mg, 0.60 mmol), 3A molecular sieves (100 mg) and benzene (5 mL) was refluxed under N2 for 3 h. After cooling, the mixture was filtered and the filtrate concentrated in vacuo. The crude imine was dissolved in dry THF (3 mL) and the solution cooled to 0° C. before addition of MeMgBr (0.2 mL of a 3N solution in THF, 0.6 mmol). The resulting mixture was stirred at 0° C. for 1 h and then quenched with saturated NH4Cl (2 mL). After diluting with water (10 mL), the mixture was extracted with CH2Cl2 (2×40 mL). The combined CH2Cl2 extracts were dried over Na2SO4 and concentrated in vacuo. The residue was purified by column chromatography (silica gel, 40:1 to 20:1 CH2Cl2/MeOH) to provide the title compound (60 mg, 33%) as a colorless oil: ESI MS m/z 360 [C19H19Cl2N2+H]+.