Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][C:2]1([C:22]#[C:23][CH2:24][CH:25]([CH3:37])[CH2:26][CH2:27][CH2:28][CH:29]([CH3:36])[CH2:30][CH2:31][CH2:32][CH:33]([CH3:35])[CH3:34])[CH2:7][CH2:6][C:5]2[C:8]([CH3:21])=[C:9]([O:14]CCCCCC)[C:10]([CH3:13])=[C:11]([CH3:12])[C:4]=2[O:3]1>[Ni].C(O)C.C(OCC)(=O)C>[CH3:13][C:10]1[C:11]([CH3:12])=[C:4]2[C:5]([CH2:6][CH2:7][C@:2]([CH2:22][CH2:23][CH2:24][C@@H:25]([CH2:26][CH2:27][CH2:28][C@@H:29]([CH2:30][CH2:31][CH2:32][CH:33]([CH3:35])[CH3:34])[CH3:36])[CH3:37])([CH3:1])[O:3]2)=[C:8]([CH3:21])[C:9]=1[OH:14]
Reactant: CCCCCCOc1c(C)c(C)c2c(c1C)CCC(C)(C#CCC(C)CCCC(C)CCCC(C)C)O2
Agent: [Ni]
Solvent: CCO
Solvent: CCOC(C)=O
Product: Cc1c(C)c2c(c(C)c1O)CC[C@@](C)(CCC[C@H](C)CCC[C@H](C)CCCC(C)C)O2
Reaction time: 6 h
Yield: 101.2 %

Procedure:
A mixture of [2S-(4R*,8R*,)]-3,4-dihydro-2,5,7,8-tetramethyl-2-(4,8,12-trimethyl-1-tridecynyl)-6-(pentylmethoxy)-2H-1-benzopyran, (200 mg, 0.39 mmol) and 40 mg of Raney Nickel in 5 mL of ethanol and 5 mL of ethyl acetate was hydrogenated at 25° C. and atmospheric pressure for 6 h. Workup in the usual manner and purification of the crude product by chromatography on silica gel (eluent 1:5 ether-hexanes) gave 170 mg of (2R,4'R,8'R)-α-tocopherol as a pale yellow oil, identical in all aspects with a known sample.
Reaction SMILES: CO[C:3]1[CH2:4][CH2:5][CH2:6][CH2:7][CH:8]([CH2:10][C:11]2[C:12]([C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=3)=[N:13][O:14][CH:15]=2)[N:9]=1.[Cl-:22].[NH4+:23]>>[ClH:22].[C:16]1([C:12]2[C:11]([CH2:10][CH:8]3[NH:9][C:3](=[NH:23])[CH2:4][CH2:5][CH2:6][CH2:7]3)=[CH:15][O:14][N:13]=2)[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1
Reactant: [Cl-]
Reactant: COC1=NC(Cc2conc2-c2ccccc2)CCCC1
Reactant: [NH4+]
Product: Cl
Product: N=C1CCCCC(Cc2conc2-c2ccccc2)N1

Procedure:
The title product of Example 127 is reacted with ammonium chloride by the method of Example 5 to generate the title compound.
Reaction SMILES: Br[C:2]1[CH:14]=[CH:13][C:5]([C:6]([NH:8][CH2:9][CH:10]2[CH2:12][CH2:11]2)=[O:7])=[C:4]([F:15])[CH:3]=1.[CH:16]1([NH:19][C:20](=[O:37])[C:21]2[CH:26]=[CH:25][C:24]([CH3:27])=[C:23](B3OC(C)(C)C(C)(C)O3)[CH:22]=2)[CH2:18][CH2:17]1.C(=O)([O-])O.[Na+]>CC(O)C.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:16]1([NH:19][C:20]([C:21]2[CH:26]=[C:25]([C:2]3[CH:14]=[CH:13][C:5]([C:6]([NH:8][CH2:9][CH:10]4[CH2:12][CH2:11]4)=[O:7])=[C:4]([F:15])[CH:3]=3)[C:24]([CH3:27])=[CH:23][CH:22]=2)=[O:37])[CH2:17][CH2:18]1
Reactant: O=C(NCC1CC1)c1ccc(Br)cc1F
Reactant: Cc1ccc(C(=O)NC2CC2)cc1B1OC(C)(C)C(C)(C)O1
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: CC(C)O
Product: Cc1ccc(C(=O)NC2CC2)cc1-c1ccc(C(=O)NCC2CC2)c(F)c1

Procedure:
4-Bromo-N-cyclopropylmethyl-2-fluorobenzamide (Intermediate 14, 60 mg), N-cyclopropyl-4-methyl-3-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-benzamide (60 mg), tetrakis(triphenylphosphine)palladium (2.5 mg) and aqueous sodiumhydrogen carbonate (1M, 1 ml) were heated in propan-2-ol (2 ml) at 85° C. for 18 hours. The reaction was concentrated under vacuum and the residue applied to a SPE (Si, 2 g) and eluted with 1:3 and 3:1 ethyl acetate/cyclohexane. The solvent was evaporated from the latter fraction under vacuum and the residue triturated with ether to give N3-cyclopropyl-N4′-(cyclopropylmethyl)-3′-fluoro-6-methyl-1,1′-biphenyl-3,4′-dicarboxamide.
Reaction SMILES: [NH2:1][C:2]1[C:3]([C:9]([NH:11][NH2:12])=[O:10])=[N:4][C:5]([Br:8])=[CH:6][N:7]=1.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.[C:35]([O:39][C:40]([NH:42][CH2:43][C:44]1[CH:45]=[C:46]([CH:50]=[CH:51][CH:52]=1)[C:47](O)=O)=[O:41])([CH3:38])([CH3:37])[CH3:36].CCN(C(C)C)C(C)C.BrP(Br)(C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>CN(C=O)C.C(OCC)(=O)C>[NH2:1][C:2]1[C:3]([C:9]2[O:10][C:47]([C:46]3[CH:45]=[C:44]([CH:52]=[CH:51][CH:50]=3)[CH2:43][NH:42][C:40](=[O:41])[O:39][C:35]([CH3:38])([CH3:36])[CH3:37])=[N:12][N:11]=2)=[N:4][C:5]([Br:8])=[CH:6][N:7]=1
Reactant: CC(C)(C)OC(=O)NCc1cccc(C(=O)O)c1
Reactant: NNC(=O)c1nc(Br)cnc1N
Agent: BrP(Br)(c1ccccc1)(c1ccccc1)c1ccccc1
Agent: CN(C)C(On1nnc2ccccc21)=[N+](C)C
Agent: F[B-](F)(F)F
Solvent: CCN(C(C)C)C(C)C
Solvent: CCOC(C)=O
Solvent: CN(C)C=O
Product: CC(C)(C)OC(=O)NCc1cccc(-c2nnc(-c3nc(Br)cnc3N)o2)c1
Temperature: 25 °C
Reaction time: 2 h

Procedure:
3-amino-6-bromo-pyrazine-2-carbohydrazide (1.2 g, 5.172 mmol), TBTU (1.333 g, 5.689 mmol), 3-[(tert-butoxycarbonylamino)methyl]benzoic acid (1.300 g, 5.172 mmol) and DIPEA (1.338 g, 1.803 mL, 10.35 mmol) in a solution in DMF (13.98 mL) were stirred at room temperature for 1 h. The reaction mixture was diluted with ethyl acetate (35 mL), washed with water (2×50 mL) and brine (1×50 mL). The organic layer was dried over MgSO4 and concentrated in vacuo to a solid. This solid was suspended in MeCN (83.89 mL) at room temperature followed by the addition of dibromo(triphenyl)phosphorane (2.183 g, 5.172 mmol) and DIPEA (1.338 g, 1.803 mL, 10.35 mmol). The resulting mixture was stirred at room temperature for 2 h and then concentrated in vacuo to leave a solid. This was purified by column chromatography on silica eluting with EtOAc/petroleum ether, Product fractions were combined and concentrated in vacuo to leave the product as a white solid. The mixture was conc. to a solid and purified by column chromatography using ethylacetate/pet ether as elaunt to afford the product as a white solid (924 mg, 40% yield); 1H NMR (400 MHz, DMSO) d 1.43 (s, 9H), 4.26 (m, 2H), 7.55 (m, 3H), 7.80 (br s, 2H), 7.97 (m, 1H) and 8.45 (s, 1H) ppm; MS (ES+) 449.08
Reaction SMILES: [C:1]1([S:7]([N:10]2[C:14]3=[N:15][CH:16]=[CH:17][CH:18]=[C:13]3[CH:12]=[CH:11]2)(=[O:9])=[O:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C([Li])CCC.CCCCCC.[CH3:30][S:31][C:32]1[CH:39]=[CH:38][C:35]([CH:36]=[O:37])=[CH:34][C:33]=1[C:40]([F:43])([F:42])[F:41]>O1CCCC1>[C:1]1([S:7]([N:10]2[C:14]3=[N:15][CH:16]=[CH:17][CH:18]=[C:13]3[CH:12]=[C:11]2[CH:36]([C:35]2[CH:38]=[CH:39][C:32]([S:31][CH3:30])=[C:33]([C:40]([F:43])([F:42])[F:41])[CH:34]=2)[OH:37])(=[O:9])=[O:8])[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1
Reactant: CSc1ccc(C=O)cc1C(F)(F)F
Reactant: O=S(=O)(c1ccccc1)n1ccc2cccnc21
Agent: [Li]CCCC
Solvent: CCCCCC
Solvent: C1CCOC1
Product: CSc1ccc(C(O)c2cc3cccnc3n2S(=O)(=O)c2ccccc2)cc1C(F)(F)F
Temperature: -78 °C
Reaction time: 0.5 h
Yield: 90.8 %

Procedure:
To a −78° C. suspension of 1-benzenesulfonyl-1H-pyrrolo[2,3-b]pyridine (2.84 g, 11 mmol) in dry tetrahydrofuran (50 mL) was added n-butyllithium in n-hexane (1.6 M, 6.9 mL, 11 mmol) dropwise. The mixture was stirred at −78° C. for 30 min before adding 4-methylsulfanyl-3-trifluoromethyl-benzaldehyde (2.65 g, 12 mmol) dropwise. The resulting mixture was stirred at −78° C. for 1 h and quenched by adding brine (20 mL). The mixture was extracted with ethyl acetate (300 mL), washed with brine, dried over anhydrous sodium sulfate and concentrated in vacuo. Purification by flash silica gel chromatography (silica gel from QingDao, 200-300 mesh, glass column from Shanghai SD company) (20% ethyl acetate/hexanes) afforded (1-benzenesulfonyl-1H-pyrrolo[2,3-b]pyridin-2-yl)-(4-methylsulfanyl-3-trifluoromethyl-phenyl)-methanol as colorless oil (4.78 g, 91%): LC/MS m/e calcd for C23H20F3N2O4S2 [M+H]+ 479.06, observed 479.0;
Reaction SMILES: [CH2:1]([O:8][C:9]([NH:11][C@H:12]1[CH2:15][N:14]([O:16][CH2:17][C:18]([OH:20])=[O:19])[C:13]1=[O:21])=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.N12CCCN=C1CCCCC2.[CH3:33][C:34]([CH3:41])([CH3:40])[C:35]([O:37][CH2:38]I)=[O:36]>CN(C)C=O.C(OCC)(=O)C>[CH2:1]([O:8][C:9]([NH:11][C@H:12]1[CH2:15][N:14]([O:16][CH2:17][C:18]([O:20][CH2:38][O:37][C:35](=[O:36])[C:34]([CH3:41])([CH3:40])[CH3:33])=[O:19])[C:13]1=[O:21])=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: O=C(O)CON1C[C@H](NC(=O)OCc2ccccc2)C1=O
Reactant: CC(C)(C)C(=O)OCI
Solvent: C1CCC2=NCCCN2CC1
Solvent: CN(C)C=O
Solvent: CCOC(C)=O
Product: CC(C)(C)C(=O)OCOC(=O)CON1C[C@H](NC(=O)OCc2ccccc2)C1=O
Temperature: 0 °C
Reaction time: 0.17 h

Procedure:
(S)-[[3-[(Benzyloxycarbonyl)amino]-2-oxo-1-azetidinyl]oxy]acetic acid (3 g; see example 79) was dissolved in 200 ml of dimethylformamide and the solution was cooled to 0° C. 1,8-diazabicyclo[5.4.0]-undec-7-ene (0.01 mol) was added followed by 2.7 g of 2,2-dimethylpropionic acid, iodomethyl ester. After 10 minutes, the mixture was diluted with 75ml of ethyl acetate, cooled (ice-water), washed with ice-cold water, ice-cold diluted sodium bicarbonate solution and again with ice-cold water. After drying (MgSO4) the filtrate was evaporated to yield 4g of the title compound, which crystallized on standing; melting point 73°-75° C.
Reaction SMILES: [OH:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[CH:7]([O:11][CH3:12])[CH:6]([CH2:13][C:14]([O:16][CH2:17][CH3:18])=[O:15])[CH2:5]2.[CH2:19]([O:26][C:27]1[CH:34]=[CH:33][C:30]([CH2:31]Cl)=[CH:29][CH:28]=1)[CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH3:25].C(=O)([O-])[O-].[K+].[K+].O>CN(C)C=O.C(OCC)(=O)C>[CH2:19]([O:26][C:27]1[CH:34]=[CH:33][C:30]([CH2:31][O:1][C:2]2[CH:3]=[C:4]3[C:8](=[CH:9][CH:10]=2)[CH:7]([O:11][CH3:12])[CH:6]([CH2:13][C:14]([O:16][CH2:17][CH3:18])=[O:15])[CH2:5]3)=[CH:29][CH:28]=1)[CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH3:25]
Reactant: CCOC(=O)CC1Cc2cc(O)ccc2C1OC
Reactant: CCCCCCCOc1ccc(CCl)cc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: CCOC(C)=O
Solvent: O
Product: CCCCCCCOc1ccc(COc2ccc3c(c2)CC(CC(=O)OCC)C3OC)cc1
Temperature: 60 °C
Reaction time: 8 h
Yield: 63.8 %

Procedure:
In 2 ml of dimethylformamide were dissolved 190 mg of ethyl 5-hydroxy-1-methoxyindane-2-acetate and 220 mg of p-heptyloxybenzyl chloride. To the solution was added 180 mg of potassium carbonate. The mixture was stirred at 60° C. overnight. After allowing to cool, water and ethyl acetate were added to the mixture. By thoroughly shaking the mixture, the organic layer was separated. After washing with water, drying and concentrating the organic layer, the residue obtained was purified by flash chromatography (eluant: toluene/ethyl acetate (25/1)) to obtain 220 mg of ethyl 5-(p-heptyloxybenzyloxy)-1-methoxy-2-indaneacetate as a colorless oily product.
Reaction SMILES: [OH:1][C:2]1[CH:11]=[CH:10][C:9]([OH:12])=[C:8]2[C:3]=1[C:4](=[O:14])[CH:5]=[CH:6][C:7]2=[O:13].[NH2:15][C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1>C(O)C>[NH:15]([C:10]1[C:9](=[O:12])[C:8]2[C:3]([C:2](=[O:1])[CH:11]=1)=[C:4]([OH:14])[C:5]([NH:15][C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)=[CH:6][C:7]=2[OH:13])[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1
Reactant: Nc1ccccc1
Reactant: O=C1C=CC(=O)c2c(O)ccc(O)c21
Solvent: CCO
Product: O=C1C(Nc2ccccc2)=CC(=O)c2c(O)c(Nc3ccccc3)cc(O)c21

Procedure:
A mixture of 1.9 g of 5,8-dihydroxy-1,4-naphthoquinone and 40 ml of aniline is heated at 100° for 8 hours. After the mixture has been cooled and diluted with ethanol, 2,6-bis-anilino-5,8-dihydroxy-1,4-naphthoquinone is obtained.
Reaction SMILES: [C:1]([OH:6])(=[O:5])[C:2]([OH:4])=[O:3].C([N:14]1[CH2:19][CH2:18][CH2:17][CH:16]([C:20]2[CH:25]=[CH:24][C:23]([O:26][C:27](=[O:29])[CH3:28])=[C:22]([O:30][C:31](=[O:33])[CH3:32])[CH:21]=2)[CH2:15]1)C1C=CC=CC=1>C(O)C.[H][H]>[C:1]([OH:6])(=[O:5])[C:2]([OH:4])=[O:3].[C:31]([O:30][C:22]1[CH:21]=[C:20]([CH:16]2[CH2:17][CH2:18][CH2:19][NH:14][CH2:15]2)[CH:25]=[CH:24][C:23]=1[O:26][C:27](=[O:29])[CH3:28])(=[O:33])[CH3:32]
Reactant: [H][H]
Reactant: CC(=O)Oc1ccc(C2CCCN(Cc3ccccc3)C2)cc1OC(C)=O
Agent: O=C(O)C(=O)O
Solvent: CCO
Product: CC(=O)Oc1ccc(C2CCCNC2)cc1OC(C)=O
Yield: 40.5 %

Procedure:
5 g of 10% palladized activated carbon were added to a solution of 10 g of the product of Step C in 600 ml of ethanol and hydrogen was introduced until hydrogen absorption ceased. The mixture was filtered and the filtrate was evaporated to dryness. The residue was dissolved in ethanol and the solution was cooled and vacuum filtered. The mother liquors were concentrated while progressively adding ethanol to a volume of 50 ml and was cooled and vacuum filtered. The recovered crystals were dried to obtain 3.25 g of 3-(3',4'-diacetoxyphenyl)-piperidine oxalate melting at 160° C.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][CH:9]([CH:14]([CH3:16])[CH3:15])[C:10](=[NH:13])[O:11][CH3:12])=[CH:4][CH:3]=1.[O:17]([C:24]1[CH:25]=[C:26]([CH:29]=[CH:30][CH:31]=1)CO)[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1>CO>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([NH:8][CH:9]([CH:14]([CH3:16])[CH3:15])[C:10](=[NH:13])[O:11][CH2:12][C:26]2[CH:29]=[CH:30][CH:31]=[C:24]([O:17][C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=3)[CH:25]=2)=[CH:6][CH:7]=1
Reactant: OCc1cccc(Oc2ccccc2)c1
Reactant: COC(=N)C(Nc1ccc(Cl)cc1)C(C)C
Solvent: CO
Product: CC(C)C(Nc1ccc(Cl)cc1)C(=N)OCc1cccc(Oc2ccccc2)c1

Procedure:
A solution of 2.25 g (10 mmol) of methyl 2-(4 -chlorophenylamino)-3-methylbutanimidate and 4.00 g (20 mmol) of 3-phenoxybenzyl alcohol is heated with continuous removal of methanol. Upon cessation of methanol evolution, there is obtained an oil, 3-phenoxybenzyl 2-(4-chlorophenylamino)-3-methylbutanimidate.
Reaction SMILES: [CH3:1][C:2]1[C:7]2[S:8][CH:9]=[CH:10][C:6]=2[CH2:5][CH2:4][N:3]=1.[CH3:11][I:12]>C(OCC)(=O)C>[I-:12].[CH3:11][N+:3]1[CH2:4][CH2:5][C:6]2[CH:10]=[CH:9][S:8][C:7]=2[C:2]=1[CH3:1]
Reactant: CI
Reactant: CC1=NCCc2ccsc21
Solvent: CCOC(C)=O
Product: CC1=[N+](C)CCc2ccsc21
Product: [I-]

Procedure:
A mixture of 4.64 g (31 mmol) 7-methyl-4,5-dihydro-thieno[2,3-c]pyridine (prepared analogously to J.Am.Chem.Soc., 1951, 1257), 8.0 ml (128 mmol) methyl iodide and 20 ml of ethyl acetate is stirred for 15 min. The precipitate formed is suction filtered, washed with ethyl acetate and dried in vacuo.
Reaction SMILES: [NH:1]1[CH2:6][CH2:5][CH:4]=[CH:3][CH2:2]1.C(=O)(O)[O-].[Na+].Cl[C:13]([O:15][CH2:16][C:17]([Cl:20])([Cl:19])[Cl:18])=[O:14]>C1C=CC=CC=1>[Cl:18][C:17]([Cl:20])([Cl:19])[CH2:16][O:15][C:13]([N:1]1[CH2:6][CH2:5][CH:4]=[CH:3][CH2:2]1)=[O:14]
Reactant: C1=CCNCC1
Reactant: O=C(Cl)OCC(Cl)(Cl)Cl
Agent: O=C([O-])O
Agent: [Na+]
Solvent: c1ccccc1
Product: O=C(OCC(Cl)(Cl)Cl)N1CC=CCC1
Temperature: 0 °C
Reaction time: 15 h

Procedure:
124.5 g (1.5 mol) of 1,2,5,6-tetrahydropyridine are dissolved in 1,200 ml of benzene. 124 g of sodium bicarbonate are introduced into this solution and the mixture is then cooled to 0° under a nitrogen atmosphere and, at this temperature, is treated slowly dropwise in the course of 31/2 hours with a solution of 316 g (1.5 mol) of 2,2,2-trichloroethyl chloroformate in 250 ml of benzene. The resulting white suspension is subsequently stirred for a further 15 hours at 0° and then poured into 2,000 ml of ice-water. The benzene phase is separated off and the aqueous phase is extracted by shaking with twice 1,000 ml of methylene chloride; the combined organic phases are washed with 1 N hydrochloric acid and then with a saturated solution of sodium chloride, dried over sodium sulphate and evaporated under a water pump vacuum, whereupon 1-(β,β,β-trichloroethoxycarbonyl)-1,2,5,6-tetrahydropyridine is obtained as a slightly reddish oil.
Reaction SMILES: [CH3:1][O:2][CH2:3][C:4]1[N:9]=[CH:8][C:7]([O:10][C:11]2[CH:12]=[C:13]3[C:17](=[C:18]([O:20][CH:21]([CH3:23])[CH3:22])[CH:19]=2)[NH:16][C:15]([C:24]([NH2:26])=O)=[CH:14]3)=[CH:6][CH:5]=1.COC1C=CC(P2(SP(C3C=CC(OC)=CC=3)(=S)S2)=[S:36])=CC=1.[C:49]([O:54][CH2:55][CH3:56])(=[O:53])[C:50]#[C:51][CH3:52].C(P(CCCC)CCCC)CCC>O1CCCC1>[CH3:1][O:2][CH2:3][C:4]1[N:9]=[CH:8][C:7]([O:10][C:11]2[CH:12]=[C:13]3[C:17](=[C:18]([O:20][CH:21]([CH3:22])[CH3:23])[CH:19]=2)[NH:16][C:15]([C:24]2[S:36][CH:51]([CH2:50][C:49]([O:54][CH2:55][CH3:56])=[O:53])[CH2:52][N:26]=2)=[CH:14]3)=[CH:6][CH:5]=1
Reactant: COCc1ccc(Oc2cc(OC(C)C)c3[nH]c(C(N)=O)cc3c2)cn1
Reactant: CC#CC(=O)OCC
Reactant: COc1ccc(P2(=S)SP(=S)(c3ccc(OC)cc3)S2)cc1
Agent: CCCCP(CCCC)CCCC
Solvent: C1CCOC1
Product: CCOC(=O)CC1CN=C(c2cc3cc(Oc4ccc(COC)nc4)cc(OC(C)C)c3[nH]2)S1
Temperature: 70 °C
Reaction time: 2 h
Yield: 50 %

Procedure:
A mixture of 5-{[6-(methoxymethyl)pyridin-3-yl]oxy}-7-(1-methylethoxy)-1H-indole-2-carboxamide (1.0 g), Lawesson's reagent (1.25 g) and tetrahydrofuran (100 mL) was stirred at 70° C. for 2 h. The mixture was concentrated in vacuo. The residue was purified by silica gel chromatography (ethyl acetate:hexane=1:9 to 1:1) to give a yellow amorphous solid. A mixture of the solid, ethyl 2-butynoate (0.78 g), tributylphosphine (565 mg) and tetrahydrofuran (50 mL) was refluxed for 15 h, and then ethyl 2-butynoate (0.78 g) and tributylphosphine (565 mg) were added to the mixture. The whole was refluxed for further 30 min, and then concentrated in vacuo. The residue was purified by basic silica gel chromatography (ethyl acetate:hexane=1:9 to 1:1, volume ratio) and then by silica gel chromatography (ethyl acetate:hexane=1:9 to 2:1) to give the title compound (0.68 g, 50%) as a yellow oil. MS 484 (MH+).
Reaction SMILES: C(=O)([O-])[O-].[Na+].[Na+].[NH2:7][CH2:8][CH2:9][CH:10]([O:14][CH2:15][CH3:16])[O:11][CH2:12][CH3:13].[C:17]1([S:23](Cl)(=[O:25])=[O:24])[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1.CC(OC)(C)C>O.C(Cl)Cl>[CH2:12]([O:11][CH:10]([O:14][CH2:15][CH3:16])[CH2:9][CH2:8][NH:7][S:23]([C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)(=[O:25])=[O:24])[CH3:13]
Reactant: CCOC(CCN)OCC
Reactant: O=S(=O)(Cl)c1ccccc1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: COC(C)(C)C
Solvent: O
Solvent: ClCCl
Product: CCOC(CCNS(=O)(=O)c1ccccc1)OCC
Temperature: 20 °C

Procedure:
To a suspension of sodium carbonate (31 g, 0.37 mol) in water (50 ml) was added a solution of 1-amino-3,3-diethoxypropane (10.00 mL, 61.81 mmol) in DCM (50 mL) followed by cooling to 0° C. benzenesulfonyl chloride (7.65 mL, 60.0 mmol) was added at 0° C. with vigorous stirring followed by warming to 20° C. and continued stirring for 2 h after which time MTBE (150 mL) was added. Organic layer was separated, washed with 1.0 M of HCl (50 mL), saturated NaHCO3 (50 g), water (50 g), concentrated and azeotroped to dry two times with MTBE (150 mL×2) to provide N-(3,3-diethoxypropyl)benzenesulfonamide, 28 (17.34 g, 60.34 mmol, 97% yield) as light yellow clear oil.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][CH:9]2[CH2:14][CH2:13][N:12](C(OCC)=O)[CH2:11][CH2:10]2)=[C:4]([N+:20]([O-:22])=[O:21])[CH:3]=1.[BrH:23]>O>[BrH:23].[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][CH:9]2[CH2:14][CH2:13][NH:12][CH2:11][CH2:10]2)=[C:4]([N+:20]([O-:22])=[O:21])[CH:3]=1
Reactant: CCOC(=O)N1CCC(Nc2ccc(Cl)cc2[N+](=O)[O-])CC1
Agent: Br
Solvent: O
Product: O=[N+]([O-])c1cc(Cl)ccc1NC1CCNCC1
Yield: 81 %

Procedure:
A mixture of 84 parts of ethyl 4[(4-chloro-2-nitrophenyl)amino]-1-piperidinecarboxylate and 750 parts of a hydrobromic acid solution 48% in water is stirred and refluxed for 4 hours. The precipitated product is filtered off, washed with water and petroleum-ether, and dried, yielding 71 parts (81%) of N-(4-chloro-2-nitrophenyl)-4-piperidinamine hydrobromide; mp. 275° C.
Reaction SMILES: [NH2:1][C:2]1[N:7]=[C:6](Cl)[CH:5]=[C:4]([CH3:9])[N:3]=1.N[CH:11]1[C:19]2[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=2)[CH2:13][CH2:12]1.C(=O)([O-])[O-].[K+].[K+].C[N:27](C)C=O>>[NH2:1][CH:2]1[N:7]=[C:6]([CH:11]2[C:19]3[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=3)[CH2:13][CH2:12]2)[CH:5]=[C:4]([CH3:9])[N:3]1[NH2:27]
Reactant: Cc1cc(Cl)nc(N)n1
Reactant: NC1CCc2ccccc21
Reactant: CN(C)C=O
Agent: O=C([O-])[O-]
Agent: [K+]
Product: CC1=CC(C2CCc3ccccc32)=NC(N)N1N
Temperature: 145 °C

Procedure:
A mixture of 2.9 g (20 mmol) of 2-amino-4-chloro-6-methylpyrimidine, 2.9 g (22 mmol) of 1-aminoindane and 4.1 g (30 mmol) of potassium carbonate in 30 ml of dimethylformamide is heated at 145° C. for 3 hours. After cooling, the reaction mixture is hydrolyzed, the aqueous mixture is extracted with methylene chloride, the separated-off organic phase is dried with sodium sulfate. After filtering off the drying agent and concentrating the organic phase by evaporation, the crude mixture is separated by means of column chromatographic separation using ethyl acetate/methanol/triethylamine 90/10/1 as eluent. The 2-amino-4-indanyl-1-amino-6-methylpyrimidine obtained in this way is taken up in ethyl acetate/heptane 2:8 and treated with activated carbon. After separating off the activated carbon and concentrating the solvent by evaporation, 1 g of 2-amino-4-indanyl-1-amino-6-methylpyrimidine is obtained (glass-like solid, m.p: 53-54° C., 20% yield, 95% purity).
Reaction SMILES: [H-].[Na+].C1COCC1.[CH3:8][O:9][C:10]1[CH:15]=[C:14]([O:16][CH3:17])[N:13]=[C:12](S(C)(=O)=O)[N:11]=1.[CH3:22][C:23]([CH3:25])=[O:24]>O>[CH3:8][O:9][C:10]1[CH:15]=[C:14]([O:16][CH3:17])[N:13]=[C:12]([CH2:22][C:23](=[O:24])[CH3:25])[N:11]=1
Reactant: COc1cc(OC)nc(S(C)(=O)=O)n1
Reactant: CC(C)=O
Agent: [H-]
Agent: [Na+]
Solvent: O
Solvent: C1CCOC1
Product: COc1cc(OC)nc(CC(C)=O)n1
Temperature: 30 °C
Yield: 22.4 %

Procedure:
In a reactor were placed 16.0 g (0.4 moles) of 60% sodium hydride, 400 ml of THF and 43.6 g (0.2 moles) of 4,6-dimethoxy-2-methanesulfonylpyrimidine. The reactor contents were heated to 30° C. Thereto was dropwise added 39.4 g (0.68 moles) of acetone, followed by a reaction for 2 hours. After the completion of the reaction, 350 ml of water was added and extraction with 500 ml of ethyl acetate was conducted. The ethyl acetate layer was concentrated. The concentrate was subjected to distillation under reduced pressure to obtain 8.8 g (44.9 m moles) of 1-(4,6-dimethoxypyrimidine-2-yl)-2-propanone. Refractive index n20D: 1.5181
Reaction SMILES: [C:1]([C:4]1[O:5][C:6]2[C:12]([O:13][CH3:14])=[CH:11][CH:10]=[CH:9][C:7]=2[CH:8]=1)(=[O:3])[CH3:2].[N+:15]([O-])([OH:17])=[O:16].C(=O)([O-])[O-].[Na+].[Na+]>C(OC(=O)C)(=O)C>[C:1]([C:4]1[O:5][C:6]2[C:12]([O:13][CH3:14])=[CH:11][CH:10]=[C:9]([N+:15]([O-:17])=[O:16])[C:7]=2[CH:8]=1)(=[O:3])[CH3:2]
Reactant: COc1cccc2cc(C(C)=O)oc12
Reactant: O=[N+]([O-])O
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: CC(=O)OC(C)=O
Product: COc1ccc([N+](=O)[O-])c2cc(C(C)=O)oc12
Temperature: 25 °C
Reaction time: 3 h

Procedure:
To a solution of 2-acetyl-7-methoxybenzofuran (4.0 g) in acetic anhydride (50 mL) at 0° C. was added 70% nitric acid (1.5 mL) drop-wise. The mixture was warmed to room temperature and stirred for 3 h then poured into ice-cold saturated sodium carbonate (200 mL). Solid sodium carbonate was added carefully with stirring until basic (pH=8). The mixture was filtered and the solid collected by vacuum filtration. The solid was boiled in 100 mL (methanol) for 1 h, then cooled to 0° C. and filtered to give 2-acetyl-7-methoxy-4-nitrobenzpfuran (2.1 g). 1H NMR (300 MHz) δ 8.29 (d,J=8.9 Hz, 1H), 8.14 (s,1H), 7.00 (d,J=8.9 Hz, 1H), 4.14 (s,3H), 2.68 (s, 3H).
Reaction SMILES: C([N:4]1[CH2:9][C:8](=[O:10])[N:7]([C:11](=[O:13])[CH3:12])[CH2:6][C:5]1=[O:14])(=O)C.C(N(CC)CC)C.[CH:22](=O)[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1.CCOC(C)=O>CN(C=O)C>[C:11]([N:7]1[CH2:6][C:5](=[O:14])[NH:4][C:9](=[CH:22][C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)[C:8]1=[O:10])(=[O:13])[CH3:12]
Reactant: CC(=O)N1CC(=O)N(C(C)=O)CC1=O
Reactant: O=Cc1ccccc1
Solvent: CCN(CC)CC
Solvent: CN(C)C=O
Solvent: CCOC(C)=O
Product: CC(=O)N1CC(=O)NC(=Cc2ccccc2)C1=O
Temperature: 25 °C
Yield: 38.3 %

Procedure:
1,4-Diacetyl-2,5-piperazinedione (25.0 g, 126 mmol), which is compound (8) mentioned in Example 3, was heated at 120°-130° C. in DMF (200 ml) with triethylamine (17.6 ml, 126 mmol) and benzaldehyde (13.0 ml, 126 mmol). After 4 h the mixture was cooled to room temperature and poured into EtOAc (1000 ml), and washed three times with brine. Any solid formed at this stage was filtered off. The filtrate was dried (MgSO4) and the solvent removed in vacuo. The residue was recrystallised from EtOAc:Hexane to give 11.78 g (38%) of the title compound as a yellow solid.