Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [NH2:1][C:2]1[C:19]([NH:20][CH:21]([C:30]2[CH:35]=[CH:34][C:33]([O:36][CH3:37])=[CH:32][CH:31]=2)[C:22]2[CH:27]=[CH:26][C:25]([O:28][CH3:29])=[CH:24][CH:23]=2)=[CH:18][CH:17]=[CH:16][C:3]=1[O:4][C:5]1[CH:14]=[C:13]([F:15])[CH:12]=[CH:11][C:6]=1[C:7]([O:9][CH3:10])=[O:8].C(N(C(C)C)C(C)C)C.[C:47](Cl)(Cl)=[O:48]>ClCCl.C1(C)C=CC=CC=1>[CH3:37][O:36][C:33]1[CH:32]=[CH:31][C:30]([CH:21]([C:22]2[CH:27]=[CH:26][C:25]([O:28][CH3:29])=[CH:24][CH:23]=2)[N:20]2[C:19]3[CH:18]=[CH:17][CH:16]=[C:3]([O:4][C:5]4[CH:14]=[C:13]([F:15])[CH:12]=[CH:11][C:6]=4[C:7]([O:9][CH3:10])=[O:8])[C:2]=3[NH:1][C:47]2=[O:48])=[CH:35][CH:34]=1
Reactant: COC(=O)c1ccc(F)cc1Oc1cccc(NC(c2ccc(OC)cc2)c2ccc(OC)cc2)c1N
Reactant: O=C(Cl)Cl
Solvent: CCN(C(C)C)C(C)C
Solvent: Cc1ccccc1
Solvent: ClCCl
Product: COC(=O)c1ccc(F)cc1Oc1cccc2c1[nH]c(=O)n2C(c1ccc(OC)cc1)c1ccc(OC)cc1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
A solution of EXAMPLE 368C (0.58 g) and N-ethyl-N-isopropylpropan-2-amine (0.804 ml) in dichloromethane (8 mL) was cooled with an ice bath. Then, a 20 wt % solution of phosgene in toluene (0.850 mil) was added dropwise. The mixture was stirred at room temperature overnight. The mixture was diluted with dichloromethane and washed with 5% aq. NaHCO3. The material was then absorbed on silica and purified on a silica gel column eluting with 50% ethyl acetate in hexane to provide the title compound.
Reaction SMILES: [NH:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[C:2]1[CH2:10][N:11]([CH:15]1[C:24]2[N:23]=[CH:22][CH:21]=[CH:20][C:19]=2[CH2:18][CH2:17][CH2:16]1)[CH2:12][CH2:13][NH2:14].C[Si]([N:29]=[C:30]=[O:31])(C)C>C(O)(C)C>[NH:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[C:2]1[CH2:10][N:11]([CH:15]1[C:24]2[N:23]=[CH:22][CH:21]=[CH:20][C:19]=2[CH2:18][CH2:17][CH2:16]1)[CH2:12][CH2:13][NH:14][C:30]([NH2:29])=[O:31]
Reactant: C[Si](C)(C)N=C=O
Reactant: NCCN(Cc1nc2ccccc2[nH]1)C1CCCc2cccnc21
Solvent: CC(C)O
Product: NC(=O)NCCN(Cc1nc2ccccc2[nH]1)C1CCCc2cccnc21
Reaction time: 20 h

Procedure:
A solution of N-(1H-benzimidazol-2-ylmethyl)-N-(5,6,7,8-tetrahydroquinolin-8-yl)-ethane-1,2-diamine (0.10 g, 0.31 mmol) in isopropanol (2 mL) was treated with trimethylsilylisocyanate (60 μL, 0.44 mmol) at room temperature. The reaction was stirred 20 hours and concentrated under reduced pressure. This afforded, after column chromatography with silica gel (2:0.5:97.5 MeOH:NH4OH:CH2Cl2), {2-[(1H-benzimidazol-2-ylmethyl)-(5,6,7,8-tetrahydroquinolin-8-yl)-amino]-ethyl}-urea (67 mg, 59%). 1H NMR (CDCl3) δ 1.68 (m, 1H), 1.86 (m, 1H), 2.02 (br, 1H), 2.23 (br, 1H), 2.65 (m, 1H), 2.82 (m, 3H), 3.17 (m, 2H), 4.00 (m, 1H), 4.07 (d, 1H, J=15.0 Hz), 4.18 (d, 1H, J=15.0 Hz), 4.43 (br, 2H, NH2), 6.00 (br, 1H, NH), 7.18 (m, 3H), 7.46 (d, 1H, J=7.0 Hz), 7.45-7.70 (br, 2H), 8.55 (d, 1H, J=4.0 Hz).
Reaction SMILES: CS[C:3]1[O:4][C:5]2[CH:11]=[CH:10][C:9]([N+:12]([O-:14])=[O:13])=[CH:8][C:6]=2[N:7]=1.[C:15]([O:19][C:20]([N:22]1[CH2:27][CH2:26][CH:25]([NH2:28])[CH2:24][CH2:23]1)=[O:21])([CH3:18])([CH3:17])[CH3:16]>CC(N(C)C)=O>[C:15]([O:19][C:20]([N:22]1[CH2:27][CH2:26][CH:25]([NH:28][C:3]2[O:4][C:5]3[CH:11]=[CH:10][C:9]([N+:12]([O-:14])=[O:13])=[CH:8][C:6]=3[N:7]=2)[CH2:24][CH2:23]1)=[O:21])([CH3:18])([CH3:16])[CH3:17]
Reactant: CC(C)(C)OC(=O)N1CCC(N)CC1
Reactant: CSc1nc2cc([N+](=O)[O-])ccc2o1
Solvent: CC(=O)N(C)C
Product: CC(C)(C)OC(=O)N1CCC(Nc2nc3cc([N+](=O)[O-])ccc3o2)CC1
Temperature: 140 °C
Yield: 23.8 %

Procedure:
A mixture of 2-methylsulfanyl-5-nitro-benzooxazole (10.0 g, 47.57 mmol, 1.0 equiv) and 4-amino-piperidine-1-carboxylic acid tert-butyl ester (14.29 g, 71.36 mmol, 1.5 equiv) in anhydrous DMAc (50 mL) was heated to 140° C. for 72 h. The solution was concentrated by evaporation under reduced pressure and the crude reaction product purified with column chromatography on silica eluting with ethyl acetate/cyclohexane (1:1) to give 4.1 g (24%) of the title compound. 1H NMR (300 MHz, CDCl3): δ 1.48 (s, 9H), 1.50-1.53 (m, 2H), 2.11-2.20 (m, 2H), 2.87-3.05 (m, 2H), 3.89-4.01 (m, 1H), 4.05-4.16 (m, 2H), 5.51 (d, J=7.5 Hz, 1H), 7.30 (d, J=8.7 Hz, 1H), 8.02 (dd, J=8.7 Hz, J=2.3 Hz, 1H), 8.18 (d, J=2.3 Hz, 1H). 13C NMR (75 MHz, CDCl3): δ 28.40, 32.29, 42.46, 50.88, 79.81, 108.36, 111.99, 116.77, 143.90, 145.23, 152.38, 154.66, 162.69. MS (ISP): 363.5 [M+H]+.
Reaction SMILES: [H-].[Na+].[I-].C[S+](C)C.[Br:8][C:9]1[C:16]([CH3:17])=[CH:15][C:12]([CH:13]=[O:14])=[CH:11][N:10]=1.[CH3:18]COC(C)=O.CCOCC>C1COCC1.CS(C)=O>[Br:8][C:9]1[C:16]([CH3:17])=[CH:15][C:12]([CH:13]2[CH2:18][O:14]2)=[CH:11][N:10]=1
Reactant: CCOC(C)=O
Reactant: Cc1cc(C=O)cnc1Br
Agent: C[S+](C)C
Agent: [H-]
Agent: [I-]
Solvent: CS(C)=O
Solvent: C1CCOC1
Solvent: CCOCC
Product: Cc1cc(C2CO2)cnc1Br
Temperature: 0 °C
Reaction time: 0.08 h
Yield: 26 %

Procedure:
To a stirred suspension of sodium hydride (1.01 g) in THF (20 ml) was added dropwise over 5 min a solution of trimethylsulfonium iodide (4.69 g) in DMSO (20 ml). The reaction mixture was stirred for 5 min and then cooled to 0° C. A solution of 6-bromo-5-methylnicotinaldehyde (4.6 g, CAS 885167-81-7) in THF (15 ml) was added dropwise. The reaction mixture was stirred at 0° C. for 30 min and then at room temperature overnight. The mixture was then poured into EtOAc/Et2O (1:1) and washed with saturated brine. The organic layer was dried over Na2SO4 and concentrated in vacuo. The residue was purified by flash column chromatography (silica gel; gradient: 0% to 50% EtOAc in hexanes) to afford (RS)-2-bromo-3-methyl-5-(oxiran-2-yl)pyridine (1.26 g, 26%) as a colourless oil. MS (ISP): 216.1 ([{81Br}M+H]+), 214.1 ([{79Br}M+H]+).
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[CH:4][C:5]([O:33][CH3:34])=[C:6]([S:8]([N:11]2[C:16]3[CH:17]=[C:18]([C:21]([NH:23][C:24]4[CH:25]=[CH:26][C:27]([C:30]([OH:32])=[O:31])=[N:28][CH:29]=4)=[O:22])[CH:19]=[CH:20][C:15]=3[O:14][CH2:13][CH2:12]2)(=[O:10])=[O:9])[CH:7]=1.[CH2:35](OC(C1C=CC(N)=CN=1)=O)[CH3:36]>>[CH2:35]([O:31][C:30]([C:27]1[CH:26]=[CH:25][C:24]([NH:23][C:21]([C:18]2[CH:19]=[CH:20][C:15]3[O:14][CH2:13][CH2:12][N:11]([S:8]([C:6]4[CH:7]=[C:2]([Cl:1])[CH:3]=[CH:4][C:5]=4[O:33][CH3:34])(=[O:10])=[O:9])[C:16]=3[CH:17]=2)=[O:22])=[CH:29][N:28]=1)=[O:32])[CH3:36]
Reactant: COc1ccc(Cl)cc1S(=O)(=O)N1CCOc2ccc(C(=O)Nc3ccc(C(=O)O)nc3)cc21
Reactant: CCOC(=O)c1ccc(N)cn1
Product: CCOC(=O)c1ccc(NC(=O)c2ccc3c(c2)N(S(=O)(=O)c2cc(Cl)ccc2OC)CCO3)cn1

Procedure:
5-{[4-(5-Chloro-2-methoxy-benzenesulfonyl)-3,4-dihydro-2H-benzo[1,4]oxazine-6-carbonyl]-amino}-pyridine-2-carboxylic acid, MS (ISP): m/e=502.0, 503.9 (M−H), was prepared as described in example 1, steps 1 to 6. Step 5 was performed using 5-amino-pyridine-2-carboxylic acid ethyl ester and yielded 5-{[4-(5-chloro-2-methoxy-benzenesulfonyl)-3,4-dihydro-2H-benzo[1,4]oxazine-6-carbonyl]-amino}-pyridine-2-carboxylic acid ethyl ester, which was hydrolyzed in step 6.
Reaction SMILES: C(OC([N:8]1[CH2:14][CH2:13][CH2:12][N:11]([C:15]2[N:19]([CH2:20][CH2:21][O:22][CH2:23][C:24]#[N:25])[C:18]3[CH:26]=[CH:27][CH:28]=[CH:29][C:17]=3[N:16]=2)[CH2:10][CH2:9]1)=O)(C)(C)C.ClCCl.CO.[IH:35]>C(OCC)C>[IH:35].[C:24]([CH2:23][O:22][CH2:21][CH2:20][N:19]1[C:18]2[CH:26]=[CH:27][CH:28]=[CH:29][C:17]=2[N:16]=[C:15]1[N:11]1[CH2:12][CH2:13][CH2:14][NH:8][CH2:9][CH2:10]1)#[N:25]
Reactant: CC(C)(C)OC(=O)N1CCCN(c2nc3ccccc3n2CCOCC#N)CC1
Agent: I
Solvent: CCOCC
Solvent: CO
Solvent: ClCCl
Product: N#CCOCCn1c(N2CCCNCC2)nc2ccccc21
Temperature: 25 °C
Reaction time: 5 h

Procedure:
Combine 1-(t-butoxycarbonyl)-4-(1-(2-cyanomethyloxyethyl)-1H-benzimidazol-2-yl)[1,4]diazepane (0.36 g, 0.91 mmol), dichloromethane (15 mL), and methanol (5 mL). Cool in an ice bath and add hydriodic acid (0.25 mL, 57%, 1.86 mmol). Warm to ambient temperature. After 5 hours, concentrate the reaction mixture in vacuo to give a residue. Combine the residue and diethyl ether (40 mL) and stir. After 18 hours, decant the solvent, add diethyl ether, and stir to give a solid. Collect the solid by filtration and dry to give the title compound.
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[C:6]([Cl:8])[N:5]=[C:4]([S:9][CH:10]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][N:13]=2)[CH3:11])[N:3]=1.[Si](OC1C=C(O[Si](C(C)(C)C)(C)C)N=C(SC(C2C=CC=CN=2)C)N=1)(C(C)(C)C)(C)[CH3:19].CI>>[NH2:1][C:2]1[CH:7]=[C:6]([Cl:8])[N:5]=[C:4]([S:9][C:10]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][N:13]=2)([CH3:19])[CH3:11])[N:3]=1
Reactant: CC(Sc1nc(O[Si](C)(C)C(C)(C)C)cc(O[Si](C)(C)C(C)(C)C)n1)c1ccccn1
Reactant: CC(Sc1nc(N)cc(Cl)n1)c1ccccn1
Solvent: CI
Product: CC(C)(Sc1nc(N)cc(Cl)n1)c1ccccn1

Procedure:
Following the procedure for the preparation of 4-amino-6-chloro-2-(1-(2-pyridyl)ethyl)thio-pyrimidine but employing an additional alkylation of 4,6-di-(tert-butyldimethylsilyloxy)-2-(1-(2-pyridyl)ethyl)thio-pyrimidine with methyl iodide, this compound is prepared. Melting Pt. 183-184.5° C.
Reaction SMILES: C[O:2][C:3](=[O:14])[C:4]1[CH:9]=[C:8]([N+:10]([O-:12])=[O:11])[CH:7]=[C:6]([Cl:13])[CH:5]=1.[OH-].[Na+]>CO.O>[Cl:13][C:6]1[CH:5]=[C:4]([CH:9]=[C:8]([N+:10]([O-:12])=[O:11])[CH:7]=1)[C:3]([OH:14])=[O:2]
Reactant: COC(=O)c1cc(Cl)cc([N+](=O)[O-])c1
Agent: [Na+]
Agent: [OH-]
Solvent: CO
Solvent: O
Product: O=C(O)c1cc(Cl)cc([N+](=O)[O-])c1
Reaction time: 2 h
Yield: 91.4 %

Procedure:
To a solution of 3-chloro-5-nitro-benzoic acid methyl ester (325, 2.75 g, 12.76 mmol) in 60 mL of MeOH was added a solution of NaOH (EM, 5.10 g, 127.6 mmol) in 35 mL of H2O. The mixture was stirred for 2 h. MeOH was removed under reduced pressure, and the mixture was diluted with water, brought to pH 2 with con. HCl. Filtration followed by washing with water gave 2.35 g (92%) desired product. 1H NMR (400 MHz, DMSO-d6) δ 14.02 (s, 1H), 8.57-8.52 (m, 2H), 8.31 (dd, J=1.9, 1.2 Hz, 1H), 3.94 (s, 3H). MS (EI): m/z 200 (M−H).
Reaction SMILES: [F:1][C:2]1[CH:3]=[CH:4][C:5]([N+:18]([O-:20])=[O:19])=[C:6]([CH:17]=1)[O:7][C@H:8]1[C@H:12]2[O:13][CH2:14][C@@H:15]([OH:16])[C@H:11]2[O:10][CH2:9]1.[OH-].[Na+].[CH2:23](Cl)Cl.S(OC)(OC)(=O)=O>[I-].C([N+](CCCC)(CCCC)CCCC)CCC>[F:1][C:2]1[CH:3]=[CH:4][C:5]([N+:18]([O-:20])=[O:19])=[C:6]([CH:17]=1)[O:7][C@H:8]1[C@H:12]2[O:13][CH2:14][C@@H:15]([O:16][CH3:23])[C@H:11]2[O:10][CH2:9]1
Reactant: ClCCl
Reactant: O=[N+]([O-])c1ccc(F)cc1O[C@@H]1CO[C@H]2[C@@H]1OC[C@H]2O
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: [I-]
Agent: [Na+]
Solvent: COS(=O)(=O)OC
Product: CO[C@@H]1CO[C@H]2[C@@H]1OC[C@H]2Oc1cc(F)ccc1[N+](=O)[O-]
Temperature: 25 °C
Reaction time: 24 h

Procedure:
To 0.9 g (3.0 mmol) (3R,3aR,6R,6aR)-6-(5-fluoro-2-nitro-phenoxy)-2,3,3a,5,6,6a-hexahydrofuro[3,2-b]furan-3-ol (III.1), 0.1 g (0.3 mmol) tetrabutylammonium iodide and 1.3 ml (7.8 mmol) of a 6 mol/l aqueous NaOH solution in 15 ml DCM 0.3 ml (3.6 mmol) dimethyl sulfate are added dropwise and the mixture is stirred at RT for 24 h. Additional 1.3 ml (7.8 mmol) of a aqueous 6 mol/l NaOH solution and 0.3 ml (3.6 mml) dimethyl sulfate are added and the mixture is stirred at RT over night. The reaction mixture is washed with water, dried and evaporated. The residue is purified by FC.
Reaction SMILES: Br[C:2]1[C:19]([NH:20][C:21](=[O:27])[CH2:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[C:18]([CH3:28])[C:5]2[CH:6]([C:9]3[CH:14]=[CH:13][C:12]([CH:15]([CH3:17])[CH3:16])=[CH:11][CH:10]=3)[CH2:7][O:8][C:4]=2[C:3]=1[CH3:29].[C:30]1(B(O)O)[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1>CCCCCC.C(OCC)(=O)C>[CH:15]([C:12]1[CH:11]=[CH:10][C:9]([CH:6]2[C:5]3[C:18]([CH3:28])=[C:19]([NH:20][C:21](=[O:27])[CH2:22][C:23]([CH3:25])([CH3:24])[CH3:26])[C:2]([C:30]4[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=4)=[C:3]([CH3:29])[C:4]=3[O:8][CH2:7]2)=[CH:14][CH:13]=1)([CH3:16])[CH3:17]
Reactant: Cc1c(Br)c(NC(=O)CC(C)(C)C)c(C)c2c1OCC2c1ccc(C(C)C)cc1
Reactant: OB(O)c1ccccc1
Solvent: CCOC(C)=O
Solvent: CCCCCC
Product: Cc1c2c(c(C)c(NC(=O)CC(C)(C)C)c1-c1ccccc1)C(c1ccc(C(C)C)cc1)CO2
Yield: 42 %

Procedure:
Using N-(6-bromo-3-(4-isopropylphenyl)-4,7-dimethyl-2,3-dihydro-1-benzofuran-5-yl)-3,3-dimethylbutanamide obtained in Example 87 and phenylboronic acid, the title compound was synthesized in the same manner as in Example 101. Yield: 42%. Melting point: 212-213° C. (hexane-ethyl acetate).
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[CH:12]=[CH:11][N:10]([C:13]3[CH:14]=[N:15][N:16]([C@@H:18]([C@:20]([C:28]4[CH:33]=[CH:32][C:31]([F:34])=[CH:30][C:29]=4[F:35])([OH:27])[CH2:21][N:22]4[CH:26]=[N:25][CH:24]=[N:23]4)[CH3:19])[CH:17]=3)[C:9]2=[O:36])=[CH:4][CH:3]=1>C(O)(=O)C.[Pd]>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[CH2:12][CH2:11][N:10]([C:13]3[CH:14]=[N:15][N:16]([C@@H:18]([C@:20]([C:28]4[CH:33]=[CH:32][C:31]([F:34])=[CH:30][C:29]=4[F:35])([OH:27])[CH2:21][N:22]4[CH:26]=[N:25][CH:24]=[N:23]4)[CH3:19])[CH:17]=3)[C:9]2=[O:36])=[CH:4][CH:3]=1
Reactant: C[C@@H](n1cc(-n2ccn(-c3ccc(Cl)cc3)c2=O)cn1)[C@](O)(Cn1cncn1)c1ccc(F)cc1F
Agent: [Pd]
Solvent: CC(=O)O
Product: C[C@@H](n1cc(N2CCN(c3ccc(Cl)cc3)C2=O)cn1)[C@](O)(Cn1cncn1)c1ccc(F)cc1F
Reaction time: 3 h
Yield: 61 %

Procedure:
3-(4-Chlorophenyl)-1-(1-((2R,3R)-3-(2,4-difluorophenyl)-3-hydroxy-4-(1H-1,2,4-triazol-1-yl)butan-2-yl)-1H-pyrazol-4-yl)-1H-imidazol-2(3H)-one obtained in Step 5 (0.026 g, 0.051 mmol) was dissolved in acetic acid (1 mL), and 5% palladium on charcoal (5% Pd/C, 0.01 g) was added thereto, and the resulting mixture was stirred for 3 hours under a hydrogen atmosphere. The reaction mixture was filtered through celite and the filtrate was concentrated by evaporation under a reduced pressure to obtain the title compound (0.016 g, yield 62%).
Reaction SMILES: CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.N1C2C(=CC=CC=2)C([C:34]2[NH:38][C:37]3[CH:39]=[CH:40][C:41]([C:43]([OH:45])=O)=[CH:42][C:36]=3[N:35]=2)=N1.[CH2:46]([NH2:53])[C:47]1[CH:52]=[CH:51][CH:50]=[CH:49][CH:48]=1.C(N(CC)C(C)C)(C)C>CN(C)C=O.CS(C)=O>[CH2:46]([NH:53][C:43]([C:41]1[CH:40]=[CH:39][C:37]2[NH:38][CH:34]=[N:35][C:36]=2[CH:42]=1)=[O:45])[C:47]1[CH:52]=[CH:51][CH:50]=[CH:49][CH:48]=1
Reactant: NCc1ccccc1
Reactant: O=C(O)c1ccc2[nH]c(-c3n[nH]c4ccccc34)nc2c1
Agent: CN(C)C(On1nnc2ccccc21)=[N+](C)C
Agent: F[P-](F)(F)(F)(F)F
Solvent: CCN(C(C)C)C(C)C
Solvent: CS(C)=O
Solvent: CN(C)C=O
Product: O=C(NCc1ccccc1)c1ccc2[nH]cnc2c1
Temperature: 20 °C
Reaction time: 1 h

Procedure:
A solution of 27.3 mg of HBTU in 0.2 ml of dimethylformamide is added, at a temperature in the region of 20° C., to a solution of 20 mg of 2-(1H-indazol-3-yl)-1H-benzimidazole-5-carboxylic acid in 0.42 ml of anhydrous dimethylformamide. After stirring at a temperature in the region of 20° C. for one hour, 15.7 ml of benzylamine are added, followed by addition of 12.4 ml of N,N-diisopropylethylamine dissolved in 0.32 ml of dimethylformamide. After 20 hours, at a temperature in the region of 20° C., the reaction medium is concentrated under reduced pressure, at a temperature in the region of 40° C. The crude residue obtained is dissolved in DMSO and purified by preparative LC-MS. The fractions containing the desired product are combined and concentrated under reduced pressure at a temperature in the region of 40° C. 20 mg of 21H-indazol-3-yl)-1H-benzimidazole-5-carboxylic acid benzylamide are thus obtained in the form of a cream-coloured powder, the characteristics of which are as follows:
Reaction SMILES: [H-].[Na+].[CH3:3][N:4]1[CH:11]=[CH:10][C:8](=[O:9])[NH:7][C:5]1=[O:6].Br[CH2:13][CH2:14][CH2:15][CH2:16][CH:17]=[CH2:18].O>CS(C)=O>[CH:13]([N:7]1[C:8](=[O:9])[CH:10]=[CH:11][N:4]([CH3:3])[C:5]1=[O:6])=[CH:14][CH2:15][CH2:16][CH2:17][CH3:18]
Reactant: Cn1ccc(=O)[nH]c1=O
Reactant: C=CCCCCBr
Agent: [H-]
Agent: [Na+]
Solvent: O
Solvent: CS(C)=O
Product: CCCCC=Cn1c(=O)ccn(C)c1=O
Reaction time: 0.25 h
Yield: 71786.3 %

Procedure:
This example illustrates a synthesis of 3-(5,6-Oxidohexyl)-1-methyluracil (inventive compound no. 1808). Sodium hydride (86 mg, 3.6 mmol) was added to a stirring solution of 1-methyluracil (500 mg, 4 mmol) in dimethyl sulfoxide (25 mL). After 15 minutes, 6-bromo-1-hexene (647 mg, 4 mmol) was added and the mixture stirred further for 20 hours. The reaction mixture was then poured into water (50 mL) and extracted with 20% ethanol/dichloromethane (3×50 mL). The combined organic layers were washed with aqueous saturated salt solution (20 mL) and dried over sodium sulfate. The solvent was evaporated under vacuum to give a residue which was purified by chromatography with silica and ethyl acetate to yield 598 g (72% yield) of 3-hexenyl-1-methyluracil (inventive compound no. 1800).
Reaction SMILES: C(NC(C)C)(C)C.C([Li])CCC.[CH2:13]([P:24](=[O:33])([O:29][CH:30]([CH3:32])[CH3:31])[O:25][CH:26]([CH3:28])[CH3:27])[CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH3:23].[C:34](=[O:36])=[O:35]>CCOCC.C1COCC1>[CH:30]([O:29][P:24]([CH:13]([CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH3:23])[C:34]([OH:36])=[O:35])([O:25][CH:26]([CH3:28])[CH3:27])=[O:33])([CH3:32])[CH3:31]
Reactant: O=C=O
Reactant: CCCCCCCCCCCP(=O)(OC(C)C)OC(C)C
Agent: [Li]CCCC
Solvent: C1CCOC1
Solvent: CC(C)NC(C)C
Solvent: CCOCC
Product: CCCCCCCCCCC(C(=O)O)P(=O)(OC(C)C)OC(C)C
Temperature: -78 °C
Reaction time: 0.25 h
Yield: 81 %

Procedure:
196 g (1.94 moles) of diisopropylamine was added to a flame-dried, 5 liter flask fitted with mechanical stirrer, condenser, thermometer and addition funnel. The flask was cooled to 0°-10° C. using a dry ice/acetone bath. 808 ml of n-butyllithium (2.4M, 1.95 moles) was slowly added, while the flask was kept at 0°-10° C. The solution was stirred for an additional 15 minutes and then chilled to -78° C. 598 g (1.84 moles) of diisopropyl undecylphosphonate was added in 1000 ml of freshly distilled THF. (The addition rate should be slow enough to maintain the temperature below -60° C.) The mixture was stirred for an additional 2 hours and then poured carefully into a 12 liter flask containing about 2 kg of dry ice in 3.78 liters of ether. This mixture was allowed to stand and warm slowly overnight. The solution was extracted with water to collect the lithium salt of the product. The organic layers contained any unreacted diisopropyl undecylphosphonate. The water layer was acidified to pH 2.0 using concentrated HCl and extracted with 500 ml of ether three times. The combined ether extracts were dried over magnesium sulfate, filtered, and flash evaporated. The product was a viscous oil weighing 553 g (81% yield) and was sufficiently pure (by 1H NMR) for use in the next step.
Reaction SMILES: [F:1][C:2]([F:14])([F:13])[O:3][C:4]1[CH:12]=[CH:11][C:7]([C:8]([OH:10])=[O:9])=[CH:6][CH:5]=1.[CH2:15]([CH:20]1[CH2:25][CH2:24][CH:23]([SiH:26]2[CH2:31][CH2:30][CH:29](O)[CH2:28][CH2:27]2)[CH2:22][CH2:21]1)[CH2:16][CH2:17][CH2:18][CH3:19]>>[F:1][C:2]([F:13])([F:14])[O:3][C:4]1[CH:12]=[CH:11][C:7]([C:8]([O:10][C@H:29]2[CH2:30][CH2:31][Si@H:26]([CH:23]3[CH2:22][CH2:21][CH:20]([CH2:15][CH2:16][CH2:17][CH2:18][CH3:19])[CH2:25][CH2:24]3)[CH2:27][CH2:28]2)=[O:9])=[CH:6][CH:5]=1
Reactant: CCCCCC1CCC([SiH]2CCC(O)CC2)CC1
Reactant: O=C(O)c1ccc(OC(F)(F)F)cc1
Product: CCCCCC1CCC([Si@H]2CC[C@H](OC(=O)c3ccc(OC(F)(F)F)cc3)CC2)CC1

Procedure:
The general procedure of Example 31 was repeated using 4-trifluoromethoxybenzoic acid and 4-(4-n-pentylcyclohexyl)-4-silacyclohexanol, thereby obtaining the intended product.
Reaction SMILES: C([N:4]1[C:12]2[C:7](=[CH:8][C:9]([F:13])=[CH:10][CH:11]=2)[C:6]([CH3:15])([CH3:14])[C:5]1=[O:16])(=O)C.Cl>C(O)(C)C.O>[F:13][C:9]1[CH:8]=[C:7]2[C:12](=[CH:11][CH:10]=1)[NH:4][C:5](=[O:16])[C:6]2([CH3:15])[CH3:14]
Reactant: CC(=O)N1C(=O)C(C)(C)c2cc(F)ccc21
Agent: Cl
Solvent: CC(C)O
Solvent: O
Product: CC1(C)C(=O)Nc2ccc(F)cc21

Procedure:
2.10 g (9.49 mmol) 1-acetyl-5-fluoro-3,3-dimethyl-1,3-dihydro-indol-2-one in 20 mL isopropanol were refluxed with 50 mL of a 6M aqueous HCl solution for 1 h. After cooling the isopropanol was eliminated i. vac. The residue was diluted with water and cooled with ice. The precipitated substance was suction filtered and washed with water. The solid was dried i. vac.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([NH:9]N)=[CH:5][CH:4]=1.[CH3:11][CH:12]([CH3:16])[C:13](=O)[CH3:14]>CC(O)=O>[CH3:1][O:2][C:3]1[CH:8]=[C:7]2[C:6](=[CH:5][CH:4]=1)[N:9]=[C:13]([CH3:14])[C:12]2([CH3:16])[CH3:11]
Reactant: CC(=O)C(C)C
Reactant: COc1ccc(NN)cc1
Solvent: CC(=O)O
Product: COc1ccc2c(c1)C(C)(C)C(C)=N2
Temperature: 100 °C
Yield: 45.4 %

Procedure:
A mixture of (4-methoxyphenyl)hydrazine (0.98 g, 7.1 mmol) and 3-methylbutan-2-one (1.53 g, 17.8 mmol) in 20 mL of HOAc was heated at 100° C. overnight. The mixture was concentrated and 1N NaOH was added until pH 9 to 10. The aqueous solution was extracted with ethyl acetate (50 mL×3). The combined organic layers were dried over Na2SO4. After filtration and concentration, the residue was purified by flash column chromatography to give 610 mg of 5-methoxy-2,3,3-trimethyl-3H-indole (45%). 1H NMR (CDCl3) δppm: 7.43 (dd, 1H), 6.81 (m, 2H), 3.83 (s, 3H), 2.26 (s, 3H), 1.28 (s, 6H). LC-MS (M+H): 190.16
Reaction SMILES: [CH2:1]([O:3][C:4](=[O:35])[CH2:5][C:6]1[CH:11]=[CH:10][C:9]([O:12][CH3:13])=[C:8]([C:14]2[C:23]([CH2:24][N:25](C(OC(C)(C)C)=O)[CH2:26][CH3:27])=[CH:22][C:21]3[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=3)[N:15]=2)[CH:7]=1)[CH3:2].[ClH:36]>C(Cl)Cl>[ClH:36].[ClH:36].[CH2:1]([O:3][C:4](=[O:35])[CH2:5][C:6]1[CH:11]=[CH:10][C:9]([O:12][CH3:13])=[C:8]([C:14]2[C:23]([CH2:24][NH:25][CH2:26][CH3:27])=[CH:22][C:21]3[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=3)[N:15]=2)[CH:7]=1)[CH3:2]
Reactant: CCOC(=O)Cc1ccc(OC)c(-c2nc3ccccc3cc2CN(CC)C(=O)OC(C)(C)C)c1
Agent: Cl
Solvent: ClCCl
Product: CCNCc1cc2ccccc2nc1-c1cc(CC(=O)OCC)ccc1OC

Procedure:
(3-{3-[(tert-Butoxycarbonyl-ethyl-amino)-methyl]-quinolin-2-yl}-4-methoxy-phenyl)-acetic acid ethyl ester (1.18 g, 2.46 mmol) in CH2Cl2 (10 mL) was treated with hydrogen chloride (4N in 1,4-dioxane; 5 mL, 20.0 mmol) at room temperature for 3 hours. The mixture was concentrated to give the title compound.
Reaction SMILES: Br[C:2]1[CH:9]=[C:8]([O:10][CH3:11])[C:7]([OH:12])=[CH:6][C:3]=1[CH:4]=[O:5].[Br:13][C:14]1[CH:19]=[CH:18][C:17](B(O)O)=[CH:16][CH:15]=1.[F-].[Cs+]>COCCOC.CO.C(Cl)Cl.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>[Br:13][C:14]1[CH:19]=[CH:18][C:17]([C:2]2[C:3]([CH:4]=[O:5])=[CH:6][C:7]([OH:12])=[C:8]([O:10][CH3:11])[CH:9]=2)=[CH:16][CH:15]=1
Reactant: COc1cc(Br)c(C=O)cc1O
Reactant: OB(O)c1ccc(Br)cc1
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: [Cs+]
Agent: [F-]
Solvent: ClCCl
Solvent: COCCOC
Solvent: CO
Product: COc1cc(-c2ccc(Br)cc2)c(C=O)cc1O
Temperature: 70 °C
Yield: 61 %

Procedure:
A mixture of 2-bromo-5-hydroxy-4-methoxy-benzaldehyde (1.00 g, 4.32 mmol), 4-bromophenyl boronic acid (1.04 g, 5.18 mmol), Pd(PPh3)4 (0.250 g), and CsF (1.97 g, 12.6 mmol) in DME/MeOH (1:1, 65 mL) was heated at 70° C. overnight. The mixture was diluted with CH2Cl2 and washed with water. The organic layer was dried over MgSO4, filtered, and the filtrate concentrated under reduced pressure. The residue was purified by flash chromatography eluting with hexane/CH2Cl2 (1:9) to give 0.809 g (60%) of the desired product which was carried into the next step without further purification. MS (DCI/NH3) m/z: 307.4 (M+H)+.
Reaction SMILES: [CH:1]1([CH2:11]Cl)[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH2:4][CH2:3][O:2]1.[NH:13]1[CH2:18][CH2:17][NH:16][CH2:15][CH2:14]1.[OH-].[Na+]>>[CH:1]1([CH2:11][N:13]2[CH2:18][CH2:17][NH:16][CH2:15][CH2:14]2)[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH2:4][CH2:3][O:2]1
Reactant: C1CNCCN1
Reactant: ClCC1OCCc2ccccc21
Agent: [Na+]
Agent: [OH-]
Product: c1ccc2c(c1)CCOC2CN1CCNCC1
Yield: 70.7 %

Procedure:
To 1 g (5.48 mmol) of (isochroman-1-yl)methyl chloride obtainable by Reference Example 1 was added 2 g (23.3 mmol) of piperazine, and the resulting mixture was heated at 100° to 120° C. for 10 hours. After being cooled, the mixture was basified with the addition of 10% sodium hydroxide and then extracted with chloroform. The extract was washed with water and then dried. The solvent was evaporated off. The residue was distilled under reduced pressure (150° C./15 mmHg) to give 0.9 g (74%) of the desired compound as an oily.