Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [C:1]([NH:4][C:5]1[CH:10]=[CH:9][C:8]([C:11]2[CH:15]=[CH:14][O:13][CH:12]=2)=[CH:7][C:6]=1[N+:16]([O-:18])=[O:17])(=O)[CH3:2].I[C:20]1[CH:21]=[C:22](C=C[CH:28]=1)[C:23]([OH:25])=[O:24].C(=O)([O-])[O-].[K+].[K+].O>CN1CCCC1=O>[C:23]([C:22]1[CH:2]=[C:1]([NH:4][C:5]2[CH:10]=[CH:9][C:8]([C:11]3[CH:15]=[CH:14][O:13][CH:12]=3)=[CH:7][C:6]=2[N+:16]([O-:18])=[O:17])[CH:28]=[CH:20][CH:21]=1)([OH:25])=[O:24]
Reactant: CC(=O)Nc1ccc(-c2ccoc2)cc1[N+](=O)[O-]
Reactant: O=C(O)c1cccc(I)c1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN1CCCC1=O
Solvent: O
Product: O=C(O)c1cccc(Nc2ccc(-c3ccoc3)cc2[N+](=O)[O-])c1

Procedure:
A mixture of 1e from Example 19 (5 g, 24.5 mmol), 3-iodobenzoic acid (6.69 g, 27 mmol), potassium carbonate (3.79 g, 27.5 mmol) and a catalytic amount of copper-bronze in 30 ml dry N-methyl-2-pyrrolidone is heated to 180° C. overnight. After cooling water is added and the mixture is washed twice with ethyl acetate. The aqueous phase is rendered acidic with diluted hydrochloric acid and the oily precipitate is filtered off. This precipitate is extracted with ethyl acetate, and the extract is purified by column-chromatography on silica gel using a mixture of ethyl acetate and petroleum ether (1:1) as the eluent. Yield: 2.56 g (32%). Mp 203-205° C.
Reaction SMILES: [C:1]1([C:7]2[C:16]3[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=3)[N:10]=[C:9]([OH:17])[CH:8]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C(N(CC)CC)C.Cl[C:26]([N:28]1[CH2:33][CH2:32][CH2:31][CH2:30][CH2:29]1)=[O:27]>CN(C)C=O>[N:28]1([C:26]([O:17][C:9]2[CH:8]=[C:7]([C:1]3[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=3)[C:16]3[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=3)[N:10]=2)=[O:27])[CH2:33][CH2:32][CH2:31][CH2:30][CH2:29]1
Reactant: Oc1cc(-c2ccccc2)c2ccccc2n1
Reactant: O=C(Cl)N1CCCCC1
Solvent: CN(C)C=O
Solvent: CCN(CC)CC
Product: O=C(Oc1cc(-c2ccccc2)c2ccccc2n1)N1CCCCC1
Yield: 13.7 %

Procedure:
The procedure is as in Example 33, but starting with 4-phenyl-2-quinolinol (2.47 g), triethylamine (2.33 cc) and 1-(chlorocarbonyl)piperidine (2.47 g) in dimethylformamide (30 cc). The residue obtained is purified by chromatography on silica gel using a cyclohexane/ethyl acetate (80:20 by volume) eluant. 4-Phenyl-2-quinolyl 1-piperidinecarboxylate (0.51 g), m.p. 85° C., is thereby isolated.
Reaction SMILES: [C:1]([O:5][C:6]([NH:8][C@H:9]([C:14]([OH:16])=O)[CH2:10][CH2:11][S:12][CH3:13])=[O:7])([CH3:4])([CH3:3])[CH3:2].[Cl:17][C:18]1[CH:24]=[CH:23][CH:22]=[CH:21][C:19]=1[NH2:20]>>[Cl:17][C:18]1[CH:24]=[CH:23][CH:22]=[CH:21][C:19]=1[NH:20][C:14](=[O:16])[C@H:9]([CH2:10][CH2:11][S:12][CH3:13])[NH:8][C:6]([O:5][C:1]([CH3:2])([CH3:3])[CH3:4])=[O:7]
Reactant: CSCC[C@H](NC(=O)OC(C)(C)C)C(=O)O
Reactant: Nc1ccccc1Cl
Product: CSCC[C@H](NC(=O)OC(C)(C)C)C(=O)Nc1ccccc1Cl

Procedure:
Reaction of N-tert-butoxycarbonyl-L-methionine (1a) and 2-chloroaniline (2b) according to General Procedure A, gave after purification on a SILICA GEL column with hexane-acetone (3:1) as the eluent, an oily liquid of (3b) (C16H23N2O3S1Cl1, 79%), Rf=0.43 (hexane-acetone 3:1), [α]D23 =-41.5° (c 0.65, CHCl3), IR (KBr) ν: 536, 548, 606, 648, 667, 691, 752, 864, 963, 1036, 1055, 1165, 1250, 1298, 1368, 1393, 1441, 1524, 1593, 1616, 1684, 1696, 2338, 2361, 2870, 2920, 2978, 3036, 3061, 3121, 3314 cm-1, 1H NMR (CDCl3) δ: 8.551 (s, 1H, Ar--NH), 8.321-8.355 (m, 1H, ArH), 7.334-7.336 (m, 1H, ArH), 7.221-7.279 (m, 1H, ArH), 7.005-7.062 (m, 1H, ArH), 5.194-5.214 (br s, 1H, NH), 4.442-4.462 (m, 1H, Hα), 2.590-2.638 (m, 2H, CH2γ), 2.144-2.281 (m, 1H, Hβ), 2.112 (s, 3H, CH3ε), 1.966-2.112 (m, 1H, Hβ), 1.44 (s, 9H, t-Bu); EIMS (70 eV) m/z (%): 358 (M+, 2).
Reaction SMILES: [I:1][C:2]1[C:3]([NH2:17])=[N:4][C:5](=[O:16])[N:6]([CH:15]=1)[C@@H:7]1[O:14][C@H:11]([CH2:12][OH:13])[C@@H:9]([OH:10])[CH2:8]1.[C:18]1([CH3:28])[CH:23]=[CH:22][C:21]([S:24](Cl)(=[O:26])=[O:25])=[CH:20][CH:19]=1.CO>N1C=CC=CC=1>[I:1][C:2]1[C:3]([NH2:17])=[N:4][C:5](=[O:16])[N:6]([CH:15]=1)[C@@H:7]1[O:14][C@H:11]([CH2:12][O:13][S:24]([C:21]2[CH:22]=[CH:23][C:18]([CH3:28])=[CH:19][CH:20]=2)(=[O:26])=[O:25])[C@@H:9]([OH:10])[CH2:8]1
Reactant: Nc1nc(=O)n([C@H]2C[C@H](O)[C@@H](CO)O2)cc1I
Reactant: Cc1ccc(S(=O)(=O)Cl)cc1
Solvent: CO
Solvent: c1ccncc1
Product: Cc1ccc(S(=O)(=O)OC[C@H]2O[C@@H](n3cc(I)c(N)nc3=O)C[C@@H]2O)cc1
Reaction time: 1 h
Yield: 79.8 %

Procedure:
To a suspension of 5-iodo-2'deoxycytidine (17.65g, 50.00 mmol) in 250 ml of dry pyridine at 0° (ice bath) is added p-toluenesulfonyl chloride (11.50g, 60.00 mmol). The reaction mixture is stirred at 0° for 1 h and then stored at 3° in the dark with stirring for an additional 23 h. At the end of the reaction a clear solution is obtained, to which 15 ml of methanol is added. After standing for 30 min, the solvent is removed under diminished pressure at room temperature to afford a syrup which is coevaporated several times with methanol. The residue is triturated with icecooled water to give a crystalline mass which is broken down to the fine particles with a spatula. The solid material is collected by filtration, washed thoroughly with water, a small amount of ice-cooled ethanol, ether, and dried in vacuo to yield 20.24 g (80%) of the desired product.
Reaction SMILES: [N:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[NH:3][C:2]=1[CH2:10][CH2:11][O:12][C:13]1[CH:29]=[CH:28][C:16]2[CH2:17][CH:18]([CH2:23][C:24]([O:26]C)=[O:25])[C:19](=[O:22])[NH:20][CH2:21][C:15]=2[CH:14]=1.N1C=CC=CC=1NCCCOC1C=CC2CC(CC(OCC)=O)C(=O)NCC=2C=1>>[N:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[NH:3][C:2]=1[CH2:10][CH2:11][O:12][C:13]1[CH:29]=[CH:28][C:16]2[CH2:17][CH:18]([CH2:23][C:24]([OH:26])=[O:25])[C:19](=[O:22])[NH:20][CH2:21][C:15]=2[CH:14]=1
Reactant: COC(=O)CC1Cc2ccc(OCCc3nc4ccccc4[nH]3)cc2CNC1=O
Agent: CCOC(=O)CC1Cc2ccc(OCCCNc3ccccn3)cc2CNC1=O
Product: O=C(O)CC1Cc2ccc(OCCc3nc4ccccc4[nH]3)cc2CNC1=O

Procedure:
According to the procedure of Example 1(c), except substituting methyl (±)-8-[2-(benzimidazol-2-yl)-1-ethoxy]-3-oxo-2,3,4,5-tetrahydro-1H-2-benzazepine-4-acetate for the ethyl (±)-8-[3-(2-pyridylamino)-1-propyloxy]-3-oxo-2,3,4,5-tetrahydro-1H-2-benzazepine-4-acetate, the title compound was prepared as a white powder: MS (ES) m/e 380.4 (M+H)+, 402.3 (M+Na)+.
Reaction SMILES: [CH3:1][N:2]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3]1.CC([O-])(C)C.[K+].[SiH:17]([CH2:22][CH3:23])([CH2:20][CH3:21])[CH2:18][CH3:19]>O1CCCC1>[CH3:1][N:2]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[C:4]([Si:17]([CH2:22][CH3:23])([CH2:20][CH3:21])[CH2:18][CH3:19])=[CH:3]1
Reactant: Cn1ccc2ccccc21
Reactant: CC[SiH](CC)CC
Agent: CC(C)(C)[O-]
Agent: [K+]
Solvent: C1CCOC1
Product: CC[Si](CC)(CC)c1cn(C)c2ccccc12
Yield: 83.9 %

Procedure:
The reaction was conducted according to the General Procedure by heating N-methylindole (66 mg, 0.5 mmol, 1 equiv.), KOt-Bu (56 mg, 0.5 mmol, 1 equiv.) and Et3SiH (88 microliters, 0.55 mmol, 1.1 equiv.) in 1 mL of tetrahydrofuran for 312 hours at 23° C. After aqueous work up, the crude reaction mixture was purified by chromatography on silica eluting with 95:5 hexanes:NEt3 (isochratic) to obtain 103 mg (84%) of the title compound as a colourless oil. 1H NMR (500 MHz, THF-d8) δ 7.63 (dt, J=7.9, 1.0 Hz, 1H), 7.32 (dt, J=8.2, 0.9 Hz, 1H), 7.15 (s, 1H), 7.12 (ddd, J=8.2, 7.0, 1.1 Hz, 1H), 7.01 (ddd, J=8.0, 7.0, 1.1 Hz, 1H), 3.78 (s, 3H), 1.06-0.95 (m, 9H), 0.95-0.83 (m, 6H). 13C NMR (126 MHz, THF-d8) δ 138.63, 135.94, 133.37, 121.44, 120.88, 118.79, 108.96, 104.39, 31.61, 7.04, 4.11. The HSQC spectrum of this reaction product as provided in FIG. 9.
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[C:4]([CH2:8][C:9]([OH:11])=[O:10])[CH:5]=[CH:6][CH:7]=1.S(Cl)(Cl)=O.[CH3:16]O>>[NH2:1][C:2]1[CH:3]=[C:4]([CH2:8][C:9]([O:11][CH3:16])=[O:10])[CH:5]=[CH:6][CH:7]=1
Reactant: CO
Reactant: Nc1cccc(CC(=O)O)c1
Solvent: O=S(Cl)Cl
Product: COC(=O)Cc1cccc(N)c1
Temperature: 0 °C

Procedure:
3-Aminophenylacetic acid (15.5 g, 0.10 mol) was suspended in methanol (150 mL) and cooled to 0° C. Thionyl chloride (11.2 mL, 0.15 mol) was added dropwise under stirring. A clear orange solution was obtained, which was stirred for 4 hours, then evaporated. The solid residue was partitioned between ethyl acetate (150 mL) and saturated sodium bicarbonate (150 mL) and the organic phase washed with saturated sodium bicarbonate (100 mL), and brine and dried (Na2SO4). Methyl 3-aminophenylacetate was isolated as a brown oil. (14.1 g, 83%). 1H NMR (500 MHz, CDCl3) δ 7.12 (1H, dd), 6.7-6.6 (3H, m), 3.71 (3H, s), 3.55 (2H, s).
Reaction SMILES: [CH2:1]([N:3]1[CH2:7][CH2:6][C@H:5]([C:8]([NH:10][CH2:11][C:12]2[CH:17]=[C:16]([F:18])[CH:15]=[CH:14][C:13]=2[S:19]([NH:22][C:23]2[C:32]([C:33]([O:35]C)=[O:34])=[C:31]3[C:26]([CH:27]4[CH2:37][CH:28]4[CH2:29][O:30]3)=[CH:25][CH:24]=2)(=[O:21])=[O:20])=[O:9])[CH2:4]1)[CH3:2].O.[OH-].[Li+].O>O1CCOCC1>[CH2:1]([N:3]1[CH2:7][CH2:6][C@H:5]([C:8]([NH:10][CH2:11][C:12]2[CH:17]=[C:16]([F:18])[CH:15]=[CH:14][C:13]=2[S:19]([NH:22][C:23]2[C:32]([C:33]([OH:35])=[O:34])=[C:31]3[C:26]([CH:27]4[CH2:37][CH:28]4[CH2:29][O:30]3)=[CH:25][CH:24]=2)(=[O:20])=[O:21])=[O:9])[CH2:4]1)[CH3:2]
Reactant: CCN1CC[C@H](C(=O)NCc2cc(F)ccc2S(=O)(=O)Nc2ccc3c(c2C(=O)OC)OCC2CC32)C1
Agent: [Li+]
Agent: [OH-]
Solvent: O
Solvent: C1COCCO1
Product: CCN1CC[C@H](C(=O)NCc2cc(F)ccc2S(=O)(=O)Nc2ccc3c(c2C(=O)O)OCC2CC32)C1
Temperature: 100 °C
Yield: 49.7 %

Procedure:
Methyl (1aRS,7bSR)-5-(2-{[((S)-1-ethylpyrrolidine-3-carbonyl)amino]methyl}-4-fluoro-benzenesulfonylamino)-1,1a,2,7b-tetrahydrocyclopropa[c]chromene-4-carboxylate (Intermediate 188, 0.190 g) and lithium hydroxide monohydrate (0.150 g) were suspended in dioxane (5 mL) and water (5 mL) and the mixture was stirred and heated at 100° C. for 18.5 hours. After cooling, the volatiles were removed in vacuo and the residue was acidified by addition of aqueous citric acid solution (10%) and extracted with DCM. The organic layer was dried (Na2SO4) and filtered. The filtrate was evaporated to dryness and the residue was purified by preparative HPLC (C18) eluting with a mixture of acetonitrile and water, containing 0.1% formic acid, with a gradient of 25-60% to give (1aRS,7bSR)-5-(2-{[((S)-1-ethylpyrrolidine-3-carbonyl)amino]methyl}-4-fluorobenzenesulfonylamino)-1,1a,2,7b-tetrahydrocyclopropa[c]chromene-4-carboxylic acid (0.092 g) as a white solid.
Reaction SMILES: S(Cl)(Cl)=O.[O:5]=[C:6]1[CH:10]([C:11]([OH:13])=[O:12])[CH2:9][CH2:8][N:7]1[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1.[CH2:20](O)[CH3:21]>>[O:5]=[C:6]1[CH:10]([C:11]([O:13][CH2:20][CH3:21])=[O:12])[CH2:9][CH2:8][N:7]1[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1
Reactant: O=C(O)C1CCN(c2ccccc2)C1=O
Reactant: CCO
Solvent: O=S(Cl)Cl
Product: CCOC(=O)C1CCN(c2ccccc2)C1=O
Temperature: 80 °C
Reaction time: 4 h
Yield: 79 %

Procedure:
Thionyl chloride is added at 0° C. (5.8 g) to a solution of 2-oxo-1-phenylpyrrolidine-3-carboxylic acid (5 g) in ethanol, and the batch is stirred at 80° C. for 4 h. When the reaction is complete, the batch is concentrated in vacuo, the residue is taken up in water and extracted with ethyl acetate. The organic phase is washed with saturated sodium bicarbonate solution and saturated sodium chloride solution and dried over sodium sulfate, giving ethyl 2-oxo-1-phenylpyrrolidine-3-carboxylate (4.5 g, 79%);
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]2[C:19]3[C:14](=[CH:15][N:16]=[C:17](F)[CH:18]=3)[N:13]=[CH:12][C:11]=2[C:21]#[N:22])[CH:5]=[CH:6][C:7]=1[F:8].[CH2:23]1[CH2:27][O:26][CH2:25][CH2:24]1>>[Cl:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]2[C:19]3[C:14](=[CH:15][N:16]=[C:17]([NH:9][C@@H:4]([CH3:3])[C@H:25]([OH:26])[C:24]4[CH:23]=[CH:27][CH:7]=[CH:6][CH:5]=4)[CH:18]=3)[N:13]=[CH:12][C:11]=2[C:21]#[N:22])[CH:5]=[CH:6][C:7]=1[F:8]
Reactant: N#Cc1cnc2cnc(F)cc2c1Nc1ccc(F)c(Cl)c1
Reactant: C1CCOC1
Product: C[C@H](Nc1cc2c(Nc3ccc(F)c(Cl)c3)c(C#N)cnc2cn1)[C@H](O)c1ccccc1
Temperature: 140 °C
Yield: 18.9 %

Procedure:
Following the procedure described above in Example 51, 4-(3-Chloro-4-fluoro-phenylamino)-6-fluoro-[1,7]naphthyridine-3-carbonitrile (0.10 g, 0.32 mmol) was reacted with (1R, 2S)-(−) norephdrine (0.96 g, 6.32 mmol) in 2 mL of THF. The reaction mixture was heated up in a sealed vial in a microwave reactor at 140° C. for 105 min. The crude product was purified by preparative HPLC and lyophilized to give a fluffy, yellow solid (26.7 mg, 18.9% yield): 1H NMR (400 MHz, DMSO-D6) δ ppm 1.09 (d, J=6.32 Hz, 3 H) 3.94-4.06 (m, 1 H) 4.73 (t, J=4.80 Hz, 1 H) 5.52 (d, J=4.29 Hz, 1 H) 6.49 (d, J=9.35 Hz, 1 H) 6.98 (s, 1 H) 7.18 (t, J=7.20 Hz, 1 H) 7.22-7.51 (m, 6 H) 7.58 (d, J=4.29 Hz, 1 H) 8.25 (s, 1 H) 8.81 (s, 1 H) 9.60 (s, 1 H); HRMS (ESI+) calcd for C24H19ClFN5O 448.13349, found (MH+) 448.1334.
Reaction SMILES: [H-].[H-].[H-].[H-].[Li+].[Al+3].[NH2:7][C:8]1[CH:9]=[CH:10][C:11]([Br:19])=[C:12]([CH:18]=1)[C:13]([N:15]([CH3:17])[CH3:16])=O.O.C(OCC)(=O)C>C1COCC1>[Br:19][C:11]1[CH:10]=[CH:9][C:8]([NH2:7])=[CH:18][C:12]=1[CH2:13][N:15]([CH3:17])[CH3:16]
Reactant: CN(C)C(=O)c1cc(N)ccc1Br
Agent: [Al+3]
Agent: [H-]
Agent: [Li+]
Solvent: C1CCOC1
Solvent: CCOC(C)=O
Solvent: O
Product: CN(C)Cc1cc(N)ccc1Br
Temperature: 0 °C
Reaction time: 2 h

Procedure:
At 0° C., LAH (1.5 g 40 mmol) was added slowly in several portions into a suspension of 5-amino-2-bromo-N,N-dimethylbenzamide (compound 26) (3.1 g, 12.7 mmol) in THF. The reaction mixture was stirred at 0° C. for 2 hours. Then at 0° C. water was added dropwise to the reaction solution slowly until there was no bubble forming in the reaction. After ethyl acetate was added, the reaction mixture was stirred for 30 minutes. The mixture was filtered, washed three times with ethyl acetate. The solvent was evaporated to give a crude product, which can be directly used for the next step.
Reaction SMILES: [Br:1][C:2]1[C:6]2[C:7](=O)[NH:8][CH:9]=[CH:10][C:5]=2[S:4][CH:3]=1.O=P(Cl)(Cl)[Cl:14]>>[Br:1][C:2]1[C:6]2[C:7]([Cl:14])=[N:8][CH:9]=[CH:10][C:5]=2[S:4][CH:3]=1
Reactant: O=c1[nH]ccc2scc(Br)c12
Reactant: O=P(Cl)(Cl)Cl
Product: Clc1nccc2scc(Br)c12
Temperature: 25 °C

Procedure:
A suspension of Example 1A (35.91 g, 0.156 mol) in POCl3 (80 mL) was heated to reflux for 2.5 hours, cooled to room temperature, poured onto 800 g of ice, and extracted repeatedly with dichloromethane. The combined extracts were washed with water and brine, dried (Na2SO4), filtered, and concentrated. The residue was purified by flash column chromatography on silica gel with 0 to 5% methanol/dichloromethane to provide 29.3 g of 3-bromo-4-chlorothieno[3,2-c]pyridine (mp 158–159° C.), which was diluted with dioxane (500 mL) and concentrated aqueous NH3 (500 mL), heated to 150° C. under pressure (260 psi) for 20 hours, and concentrated. The residue was triturated from MTBE then from methanol to provide 20.29 g of the desired product. m.p. 153–155° C.
Reaction SMILES: CO[CH:3]1[C:8]2[S:9][CH:10]=[CH:11][C:7]=2[CH:6]([N:12]=[C:13]=[O:14])[CH2:5][CH2:4]1.C(N)C#C.CON.NO.C(ON)CCC.[CH3:30][NH:31][O:32][CH3:33]>>[CH3:30][N:31]([O:32][CH3:33])[C:13]([NH:12][CH:6]1[C:7]2[CH:11]=[CH:10][S:9][C:8]=2[CH2:3][CH2:4][CH2:5]1)=[O:14]
Reactant: CNOC
Reactant: COC1CCC(N=C=O)c2ccsc21
Agent: C#CCN
Agent: CCCCON
Agent: CON
Product: CON(C)C(=O)NC1CCCc2sccc21

Procedure:
Similarly, 4,5,6,7-tetrahydro-7-methoxybenzo[b]-thien-4-ylisocyanate is allowed to react with propargylamine, methoxyamine, hydroxylamine, n-butoxyamine and methylmethoxyamine to afford 1-propynyl-, 1-methoxy-, 1-hydroxy-, 1(-n-butoxy)-, and 1-methyl-1-methoxy-3-(4,5,6,7-tetrahydrobenzo[b]thien-4-yl)urea, respectively.
Reaction SMILES: [CH3:1][N:2]([CH3:28])[C:3]([CH:5]1[CH2:10][CH2:9][N:8]([CH2:11][C:12]2[S:20][C:19]3[C:18]([N:21]4[CH2:26][CH2:25][O:24][CH2:23][CH2:22]4)=[N:17][C:16](Cl)=[N:15][C:14]=3[CH:13]=2)[CH2:7][CH2:6]1)=[O:4].[CH3:29][O:30][C:31]1[N:36]=[C:35]([O:37][CH3:38])[C:34](B2OC(C)(C)C(C)(C)O2)=[CH:33][N:32]=1>>[CH3:29][O:30][C:31]1[N:36]=[C:35]([O:37][CH3:38])[C:34]([C:16]2[N:17]=[C:18]([N:21]3[CH2:26][CH2:25][O:24][CH2:23][CH2:22]3)[C:19]3[S:20][C:12]([CH2:11][N:8]4[CH2:9][CH2:10][CH:5]([C:3]([N:2]([CH3:28])[CH3:1])=[O:4])[CH2:6][CH2:7]4)=[CH:13][C:14]=3[N:15]=2)=[CH:33][N:32]=1
Reactant: CN(C)C(=O)C1CCN(Cc2cc3nc(Cl)nc(N4CCOCC4)c3s2)CC1
Reactant: COc1ncc(B2OC(C)(C)C(C)(C)O2)c(OC)n1
Product: COc1ncc(-c2nc(N3CCOCC3)c3sc(CN4CCC(C(=O)N(C)C)CC4)cc3n2)c(OC)n1

Procedure:
1-(2-Chloro-4-morpholin-4-yl-thieno[3,2-d]pyrimidin-6-ylmethyl)-piperidine-4-carboxylic acid dimethylamide was reacted with 2,4-dimethoxy-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-pyrimidine in General Procedure A. Purification on silica yielded 125. NMR (CDCl3): 1.74 (m, 2H, CH2), 2.02 (m, 2H, CH2), 2.17 (m, 2H, CH2), 2.55 (m, H, CH), 2.97 (s, 3H, CH3), 3.04-3.07 (m+s, 5H, CH2+CH3), 3.84 (s, 2H, CH2), 3.88-3.90 (m, 4H, 2×CH2), 4.03-4.05 (m, 4H, 2×CH2), 4.08 (s, 3H, CH3), 4.11 (s, 3H, CH3), 7.30 (s, H, ArH), 8.93 (s, H, ArH). MS: (ESI+): MH+=528.45
Reaction SMILES: [F:1][C:2]([F:21])([F:20])[C:3]1[CH:4]=[C:5]([N:9]2[C:14]3[N:15]=[CH:16][CH:17]=[CH:18][C:13]=3[CH2:12][NH:11][C:10]2=[O:19])[CH:6]=[CH:7][CH:8]=1.CN(C)C=O.[CH2:27](OC(OCC)N(C)C)[CH3:28]>O>[F:21][C:2]([F:20])([F:1])[C:3]1[CH:4]=[C:5]([N:9]2[C:14]3[N:15]=[CH:16][CH:17]=[CH:18][C:13]=3[CH2:12][N:11]([CH2:27][CH3:28])[C:10]2=[O:19])[CH:6]=[CH:7][CH:8]=1
Reactant: CCOC(OCC)N(C)C
Reactant: O=C1NCc2cccnc2N1c1cccc(C(F)(F)F)c1
Solvent: CN(C)C=O
Solvent: O
Product: CCN1Cc2cccnc2N(c2cccc(C(F)(F)F)c2)C1=O
Yield: 18.9 %

Procedure:
To a mixture of 2.9 g of 1-(m-trifluoromethylphenyl)-2-oxo-1,2,3,4-tetrahydropyrido[2,3-d]pyrimidine, 25 ml of dimethylformamide and 4.4 g of dimethylformamide diethylacetal was reacted at 145° - 150° C for 5 hours. After the reaction was complete, the solvent was distilled off from the mixture under reduced pressure. The residue thus obtained was diluted with water, extracted with ether and dehydrated. The ether solution was applied on a column of alumina and then eluted with ether. The eluate was concentrated by evaporation to leave a residue, which was then recrystallized from a mixture of ether and petroleum ether to give 0.6 g of 1-(m-trifluoromethylphenyl)-3-ethyl-2-oxo-1,2,3,4-tetrahydropyrido[2,3-d]pyrimidine as colorless prisms, melting at 155° - 157° C.
Reaction SMILES: [C:1]([OH:8])(=[O:7])/[CH:2]=[CH:3]/[C:4]([OH:6])=[O:5].C([O-])(=O)C.[Mo+4:13].C([O-])(=O)C.C([O-])(=O)C.C([O-])(=O)C>CO>[Mo:13].[C:1]([OH:8])(=[O:7])/[CH:2]=[CH:3]/[C:4]([OH:6])=[O:5]
Reactant: [Mo+4]
Agent: CC(=O)[O-]
Agent: O=C(O)/C=C/C(=O)O
Solvent: CO
Product: [Mo]
Temperature: 25 °C
Reaction time: 72 h

Procedure:
0.597 g (5.14 mmol) of fumaric acid and 1,000 g (2.34 mmol) of molybdenum acetate were dissolved in 900 ml of methanol. After this was stirred for three days at the room temperature, this was kept still for a few days. Thereafter, its precipitation product was suction-filtered, rinsed sufficiently with methanol and then vacuum-dried for 60° C./4 hours, whereby 0.970 g of target substance was obtained. This substance had the specific surface area of 469 m2 /g. And, a measurement according to the HK method using argon revealed that the substance had the pore diameter of 5.8 Å.
Reaction SMILES: [CH2:1]([O:3][C:4]([CH:6]1[CH2:11][CH2:10][NH:9][CH2:8][CH2:7]1)=[O:5])[CH3:2].C(N(C(C)C)C(C)C)C.C1(C)C=CC(S(O[CH2:31][CH2:32][CH:33]2[CH2:42][CH2:41][C:40]3[C:35](=[CH:36][CH:37]=[CH:38][CH:39]=3)[O:34]2)(=O)=O)=CC=1>CN(C)C=O>[CH2:1]([O:3][C:4]([CH:6]1[CH2:11][CH2:10][N:9]([CH2:31][CH2:32][CH:33]2[CH2:42][CH2:41][C:40]3[C:35](=[CH:36][CH:37]=[CH:38][CH:39]=3)[O:34]2)[CH2:8][CH2:7]1)=[O:5])[CH3:2]
Reactant: Cc1ccc(S(=O)(=O)OCCC2CCc3ccccc3O2)cc1
Reactant: CCOC(=O)C1CCNCC1
Solvent: CCN(C(C)C)C(C)C
Solvent: CN(C)C=O
Product: CCOC(=O)C1CCN(CCC2CCc3ccccc3O2)CC1
Reaction time: 16 h
Yield: 74.8 %

Procedure:
First 1.57 g (10 mmol) of piperidine-4-carboxylic acid ethyl ester and then 2.07 g (16 mmol) of N-ethyl-N,N-diisopropylamine are added to a solution of 2.66 g (8 mmol) of 2-[2-(p-toluenesulphonyloxy)ethyl]chroman in 35 ml of absolute dimethylformamide. The mixture is stirred for 16 hours at 60° and then, after cooling, is concentrated by evaporation under a high vacuum. Water is added to the oily residue and extraction is carried out with diethyl ether. The combined organic phases are washed with water and extracted with 2N hydrochloric acid. The combined hydrochloric acid extracts are rendered alkaline, while cold, with sodium hydroxide solution (30% strength) and extracted with dichloromethane. The combined dichloromethane phases are dried over sodium sulphate and concentrated by evaporation in vacuo. 2.17 g (85.7%) of crude product are obtained and are chromatographed on 110 g of silica gel (0.040-0.063 mm) using ethyl acetate as the eluant. 1.90 g (75.1%) of 1-[2 -(chroman-2-yl)ethyl]-piperidine-4-carboxylic acid ethyl ester are thus obtained in the form of a yellow oil. The 1-[2-(chroman-2-yl)ethyl]-piperidine-4-carboxylic acid ethyl ester hydrochloride produced therefrom using hydrochloric acid in diethyl ether crystallises from ethanol/diethyl ether and melts at 190°-192°.
Reaction SMILES: [Br:1][C:2]1[CH:3]=[N:4][C:5]([Si:8]([CH3:11])([CH3:10])[CH3:9])=[CH:6][CH:7]=1.[C:12](O)(=O)[C:13](C)([CH3:15])[CH3:14].S(=O)(=O)(O)O.[NH4+].[NH4+].[O-]S(OOS([O-])(=O)=O)(=O)=O.C(=O)=O>O.[N+]([O-])([O-])=O.[Ag+].C(OCC)(=O)C>[C:13]([C:3]1[C:2]([Br:1])=[CH:7][CH:6]=[C:5]([Si:8]([CH3:11])([CH3:10])[CH3:9])[N:4]=1)([CH3:15])([CH3:14])[CH3:12]
Reactant: CC(C)(C)C(=O)O
Reactant: C[Si](C)(C)c1ccc(Br)cn1
Agent: [Ag+]
Agent: O=C=O
Agent: O=S(=O)(O)O
Solvent: CCOC(C)=O
Solvent: O
Product: CC(C)(C)c1nc([Si](C)(C)C)ccc1Br
Temperature: 25 °C

Procedure:
Procedure analogous to WO 2007/073303: 12.4 g (73 mmol) of silver nitrate are added to a mixture of 128.8 g (560 mmol) of 3-bromo-6-trimethylsilylpyridine [291312-74-8], 286.0 g (2.8 mol) of pivalic acid [75-98-9] and 400 ml of water, and the mixture is stirred at room temperature for min. 1000 ml of 10% by weight sulfuric acid are added dropwise to the reaction mixture over the course of 15 min., the mixture is warmed to 70° C., and a solution of 168.5 g (730 mmol) of ammonium peroxodisulfate in 300 ml of water is added dropwise over the course of 30 min. When the evolution of carbon dioxide is complete, the mixture is stirred at 70° C. for a further 3 h, the reaction mixture is allowed to cool, 500 ml of ethyl acetate are added, the aqueous phase is separated off, extracted again with 500 ml of ethyl acetate, the organic phases are combined, washed ten times with 300 ml of sat. sodium hydrogencarbonate solution each time, finally washed once with 500 ml of sat. sodium chloride solution, dried over magnesium sulfate, the solvent is removed in vacuo, and the oil obtained in this way is dried at 60° C. in an oil-pump vacuum. Yield: 59.4 g (207 mmol), 37%. Purity: >95% according to 1H-NMR.
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[SH:8].[CH:9](=O)[C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1>C1(C)C(C)=CC=CC=1>[C:10]1([C:9]2[S:8][C:3]3[CH:4]=[CH:5][CH:6]=[CH:7][C:2]=3[N:1]=2)[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1
Reactant: Nc1ccccc1S
Reactant: O=Cc1ccccc1
Solvent: Cc1ccccc1C
Product: c1ccc(-c2nc3ccccc3s2)cc1
Temperature: 120 °C
Reaction time: 13 h

Procedure:
2-Aminothiophenol (0.856 ml, 8 mmol), benzaldehyde (0.813 ml, 8 mmol), 1 g of an oxidation catalyst and 15 ml of xylene as solvent were charged into a 100 ml three-neck flask, and were stirred at 120° C. for 13 hours under an oxygen atmosphere. The reaction mixture was filtered through Celite, and then the Celite and the oxidation catalyst were washed with ethyl acetate. The filtrate was condensed with a rotary evaporator to yield a solid. The solid was recrystallized from diethyl ether. Resulting colorless crystals were then weighed and the yield thereof was defined as a reaction yield.