Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: Cl[CH2:2][C:3]1[CH:8]=[CH:7][C:6]([CH2:9][CH2:10][C:11]2[N:12]=[C:13]([NH:16][C:17](=[O:19])[CH3:18])[S:14][CH:15]=2)=[CH:5][C:4]=1[F:20].[N-:21]=[N+:22]=[N-:23].[Na+].O.C(OCC)(=O)C>CN(C)C=O>[N:21]([CH2:2][C:3]1[CH:8]=[CH:7][C:6]([CH2:9][CH2:10][C:11]2[N:12]=[C:13]([NH:16][C:17](=[O:19])[CH3:18])[S:14][CH:15]=2)=[CH:5][C:4]=1[F:20])=[N+:22]=[N-:23]
Reactant: CC(=O)Nc1nc(CCc2ccc(CCl)c(F)c2)cs1
Reactant: [N-]=[N+]=[N-]
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: O
Solvent: CCOC(C)=O
Product: CC(=O)Nc1nc(CCc2ccc(CN=[N+]=[N-])c(F)c2)cs1
Temperature: 25 °C
Reaction time: 3.5 h
Yield: 77.4 %

Procedure:
To a solution of N-(4-{2-[4-(chloromethyl)-3-fluorophenyl]ethyl}-1,3-thiazol-2-yl)acetamide (203.3 mg, 0.650 mmol) in anhydrous N,N-dimethylformamide (2 ml) was added sodium azide (233.7 mg, 3.595 mmol), and the mixture was stirred at room temperature for 3.5 hr. Water (20 ml) and ethyl acetate (20 ml) were added to the reaction mixture, and the mixture was stirred, stood still and then partitioned. The aqueous layer was extracted with ethyl acetate, and the combined organic layer was washed with water and saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. Diisopropyl ether (10 ml) was added to the residue, and the mixture was filtered and dried under reduced pressure to give N-(4-{2-[4-(azidomethyl)-3-fluorophenyl]ethyl}-1,3-thiazol-2-yl)acetamide (160.5 mg, 0.503 mmol, yield 77.3%) as a white solid.
Reaction SMILES: Br[C:2]([Br:5])(Br)Br.[CH:6]12[O:14][CH:9]([CH:10](CO)[CH2:11]1)[CH:8]=[CH:7]2.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>C(Cl)Cl>[CH:9]12[O:14][CH:6]([CH:11]([CH2:2][Br:5])[CH2:10]1)[CH:7]=[CH:8]2
Reactant: OCC1CC2C=CC1O2
Reactant: BrC(Br)(Br)Br
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: ClCCl
Product: BrCC1CC2C=CC1O2
Temperature: 0 °C
Reaction time: 12 h

Procedure:
Tetrabromomethane (1.161 g, 3.50 mmol) was added to a solution of 7-oxanorborn-2-en-5-ylmethanol (0.305 g, 2.50 mmol, from Example 2) in CH2Cl2 (12.5 ml). The solution was cooled to 0° C. and admixed with triphenylphosphine (1.836 g, 7 mmol). The reaction mixture was allowed to warm to room temperature and stirred for 12 h. The solvent was removed under reduced pressure and the remaining solid was taken up in cyclohexane. The crude product was purified by flash chromatography (using a 98:2 mixture of cyclohexane and ethyl acetate). 0.3 g (59% of theory) of the pure product were obtained. The product was stored under cool conditions with the exclusion of light.
Reaction SMILES: [CH3:1][N:2]([CH2:4][C@@H:5]1[CH2:8][C@H:7]([C:9]2[N:13]3[CH:14]=[CH:15][N:16]=[C:17]([NH2:18])[C:12]3=[C:11]([C:19]3[CH:24]=[CH:23][C:22]([O:25][C:26]4[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=4)=[CH:21][CH:20]=3)[N:10]=2)[CH2:6]1)[CH3:3].N1CC[CH2:34][CH2:33]1>>[O:25]([C:22]1[CH:21]=[CH:20][C:19]([C:11]2[N:10]=[C:9]([CH:7]3[CH2:6][CH:5]([CH2:4][N:2]4[CH2:1][CH2:34][CH2:33][CH2:3]4)[CH2:8]3)[N:13]3[CH:14]=[CH:15][N:16]=[C:17]([NH2:18])[C:12]=23)=[CH:24][CH:23]=1)[C:26]1[CH:27]=[CH:28][CH:29]=[CH:30][CH:31]=1
Reactant: C1CCNC1
Reactant: CN(C)C[C@H]1C[C@@H](c2nc(-c3ccc(Oc4ccccc4)cc3)c3c(N)nccn32)C1
Product: Nc1nccn2c(C3CC(CN4CCCC4)C3)nc(-c3ccc(Oc4ccccc4)cc3)c12

Procedure:
Prepared according to the procedure described above for cis-3-(3-dimethylaminomethylcyclobutyl)-1-(4-phenoxyphenyl)-imidazo[1,5-a]pyrazin-8-ylamine, except using pyrrolidine.
Reaction SMILES: CN([CH:9]=[O:10])C1C=CC=CC=1.P(Cl)(Cl)(Cl)=O.[CH3:16][C:17]1[CH:18]=[C:19]([O:24][CH2:25][CH:26]=[CH2:27])[CH:20]=[C:21]([CH3:23])[CH:22]=1>>[CH2:25]([O:24][C:19]1[CH:20]=[C:21]([CH3:23])[C:22]([CH:9]=[O:10])=[C:17]([CH3:16])[CH:18]=1)[CH:26]=[CH2:27]
Reactant: C=CCOc1cc(C)cc(C)c1
Reactant: CN(C=O)c1ccccc1
Solvent: O=P(Cl)(Cl)Cl
Product: C=CCOc1cc(C)c(C=O)c(C)c1
Temperature: 70 °C
Reaction time: 0.42 h
Yield: 51 %

Procedure:
N-methyl formanilide, 20.5 ml (166 mmole), was chilled to 13° , where it began to solidify. Phosphorus oxychloride, 14.4 ml (155 mmole), was added with stirring, under nitrogen. After 25 minutes, the temperature was 45°. 3,5-Dimethylallyloxy benzene, 16.2 g (100 mmole), prepared as describe above, was added with stirring and heated in a 70° C. oil bath. The reaction exothermed to 93° C. and was stirred under nitrogen for 30 minutes. The bath was removed and when the temperature reached 35°, the product was dissolved in chloroform. Ice was added, the layers were separated and washed once with water, twice with sodium bicarbonate, once with water and once with brine. The product was chromatographed down 500 ml of silica, eluting with chloroform to give 9.67 g (51%) of subtitled product which was used without further purification.
Reaction SMILES: [Br:1][C:2]1[CH:11]=[C:10]2[C:5]([C:6]([CH3:21])([CH3:20])[CH2:7][C:8](C=O)([CH2:13][CH2:14][C:15](=[O:17])[CH3:16])[C:9]2=O)=[CH:4][CH:3]=1.O.[OH-].[Li+]>CO.O>[Br:1][C:2]1[CH:11]=[C:10]2[C:5](=[CH:4][CH:3]=1)[C:6]([CH3:20])([CH3:21])[CH2:7][C:8]1[CH2:13][CH2:14][C:15](=[O:17])[CH2:16][C:9]2=1
Reactant: CC(=O)CCC1(C=O)CC(C)(C)c2ccc(Br)cc2C1=O
Agent: [Li+]
Agent: [OH-]
Solvent: CO
Solvent: O
Product: CC1(C)CC2=C(CC(=O)CC2)c2cc(Br)ccc21
Temperature: 25 °C
Reaction time: 0.75 h
Yield: 25 %

Procedure:
A solution of 7-bromo-4,4-dimethyl-2-formyl-2-(3-oxo-butyl)-1-oxo-1,2,3,4-tetrahydronaphthalene (1.71 g, 4.87 mmol) in methanol (170 ml) was treated with a solution of lithium hydroxide hydrate (0.854 g, 20.35 mmol) in water (85 ml) the reaction was stirred at room temperature for 45 minutes and then the temperature was raised to 50° C. and the mixture was stirred for another 2 hours. The reaction was quenched with water and adjusted to pH 5 with 4M hydrochloric acid. The aqueous phases were extracted with ethylacetate (3×) and the combined organic phases were washed with water and dried over anhydrous magnesium sulfate. The residue was purified by silica gel chromatography (hexane/ethylacetate 95:5 to 90:10) to give the title material (0.631 g, 42%) along with 6-bromo-9,9-dimethyl-3-oxo-1,2,3,4,9,10-hexahydrophenanthrene (0.371 g, 25%).
Reaction SMILES: CC(C)([O-])C.[Na+].C1(P(C2CCCCC2)C2C=CC=CC=2C2C=CC=CC=2N(C)C)CCCCC1.[CH3:35][C:36]1([CH3:50])[C:40]([CH3:42])([CH3:41])[O:39][B:38]([C:43]2[CH:49]=[CH:48][C:46]([NH2:47])=[CH:45][CH:44]=2)[O:37]1.Br[C:52]1[CH:57]=[CH:56][CH:55]=[C:54]([O:58][CH2:59][C:60]2[CH:65]=[CH:64][CH:63]=[CH:62][CH:61]=2)[N:53]=1>C(O)(C)(C)C.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd]>[CH2:59]([O:58][C:54]1[N:53]=[C:52]([NH:47][C:46]2[CH:48]=[CH:49][C:43]([B:38]3[O:37][C:36]([CH3:50])([CH3:35])[C:40]([CH3:41])([CH3:42])[O:39]3)=[CH:44][CH:45]=2)[CH:57]=[CH:56][CH:55]=1)[C:60]1[CH:61]=[CH:62][CH:63]=[CH:64][CH:65]=1
Reactant: Brc1cccc(OCc2ccccc2)n1
Reactant: CC1(C)OB(c2ccc(N)cc2)OC1(C)C
Agent: [Pd]
Agent: CC(C)(C)[O-]
Agent: CN(C)c1ccccc1-c1ccccc1P(C1CCCCC1)C1CCCCC1
Solvent: CC(C)(C)O
Product: CC1(C)OB(c2ccc(Nc3cccc(OCc4ccccc4)n3)cc2)OC1(C)C
Yield: 65 %

Procedure:
Sodium tert-butoxide (556 mg, 5.78 mmol), 2-Dicyclohexylphosphino-2′-(N,N-dimethylamino)biphenyl (98 mg, 0.25 mmol), Bis(dibenzylideneacetone)palladium(0) (96 mg, 0.17 mmol), 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)aniline (ou) (1.00 g, 4.57 mmol) and 2-Bromo-6-benzyloxypyridine (ot) (1.10 g, 4.15 mmol) were mixed in tert-Butyl alcohol (20 mL), which was purged by nitrogen for a few minutes. The dark orange mixture was microwaved at 120° C. for 15 minutes, and the reaction was quenched by 10% citric acid (aqueous). After purification on silica gel column, the desired product ow (1.08 g 65% yield) was obtained as slightly brown solid: 1H NMR (400 MHz, CDCl3) δ 7.75 (d, J=8.4 Hz, 2H), 7.49-7.41 (m, 3H), 7.41-7.34 (m, 4H), 7.34-7.27 (m, 1H), 6.46 (s, 1H), 6.44 (d, J=7.9 Hz, 1H), 6.30 (d, J=7.9 Hz, 1H), 5.37 (s, 2H), 1.34 (s, 12H); LC-MS m/z=403 (M+H).
Reaction SMILES: [NH2:1][C:2]1[N:10]=[C:9]2[C:5]([N:6]=[CH:7][N:8]2[CH2:11][CH:12]([CH2:17][C:18]([O:20][CH3:21])=[O:19])[C:13]([O:15][CH3:16])=[O:14])=[C:4](Cl)[N:3]=1.C([O-])(=O)C.[Na+]>[Pd].C(O)C>[NH2:1][C:2]1[N:10]=[C:9]2[C:5]([N:6]=[CH:7][N:8]2[CH2:11][CH:12]([CH2:17][C:18]([O:20][CH3:21])=[O:19])[C:13]([O:15][CH3:16])=[O:14])=[CH:4][N:3]=1
Reactant: COC(=O)CC(Cn1cnc2c(Cl)nc(N)nc21)C(=O)OC
Agent: [Pd]
Agent: CC(=O)[O-]
Agent: [Na+]
Solvent: CCO
Product: COC(=O)CC(Cn1cnc2cnc(N)nc21)C(=O)OC
Reaction time: 115 h

Procedure:
A mixture of dimethyl 2-(2-amino-6-chloropurin-9-ylmethyl)succinate (3.28 g, 10 mmol), sodium acetate (1.5 g) and 5% palladium on charcoal (0.4 g) in ethanol (200 ml) was hydrogenated with agitation in a Parr apparatus at 40 psi for 115 h/room temperature. After filtration, sodium acetate (1.6 g) and 5% Pd/C (0.4 g) were added and the hydrogenation was continued for 70 h. After filtration and evaporation to dryness, the residue was extracted with 2×50 ml of chloroform and the combined extracts were evaporated to dryness affording 2.6 g (89%) of crude dechlorinated product.
Reaction SMILES: [C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH2:11][CH2:10][CH:9]1[CH2:14][CH2:15][O:16][C:17]1[C:26]2[C:21](=[CH:22][C:23]([Cl:30])=[C:24]([C:27]([OH:29])=O)[CH:25]=2)[NH:20][C:19](=[O:31])[C:18]=1[C:32]1[S:33][C:34]([Cl:37])=[CH:35][CH:36]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].Cl.C[N:40](C)[CH2:41][CH2:42][CH2:43][N:44]=[C:45]=[N:46]CC.NC1C=CN=CN=1>CN(C)C1C=CN=CC=1.C(Cl)Cl>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH2:11][CH2:10][CH:9]1[CH2:14][CH2:15][O:16][C:17]1[C:26]2[C:21](=[CH:22][C:23]([Cl:30])=[C:24]([C:27](=[O:29])[NH:40][C:41]3[CH:42]=[CH:43][N:44]=[CH:45][N:46]=3)[CH:25]=2)[NH:20][C:19](=[O:31])[C:18]=1[C:32]1[S:33][C:34]([Cl:37])=[CH:35][CH:36]=1)=[O:7])([CH3:4])([CH3:2])[CH3:3]
Reactant: CC(C)(C)OC(=O)N1CCCCC1CCOc1c(-c2ccc(Cl)s2)c(=O)[nH]c2cc(Cl)c(C(=O)O)cc12
Reactant: CCN=C=NCCCN(C)C
Agent: CN(C)c1ccncc1
Agent: Cl
Agent: Nc1ccncn1
Solvent: ClCCl
Product: CC(C)(C)OC(=O)N1CCCCC1CCOc1c(-c2ccc(Cl)s2)c(=O)[nH]c2cc(Cl)c(C(=O)Nc3ccncn3)cc12
Temperature: 25 °C
Reaction time: 18 h
Yield: 40.5 %

Procedure:
To a solution of 4-[2-(1-tert-butoxycarbonylpiperidin-2-yl)-ethoxy]-7-chloro-3-(5-chlorothiophen-2-yl)-2-oxo-1,2-dihydroquinoline-6-carboxylic acid (37 mg in 0.50 mL dry methylene chloride) was added 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDC, 37 mg) followed by 4-dimethylaminopyridine (8 mg) and 4-aminopyrimidine (18 mg) and the mixture stirred at room temperature. After 18 hours, the mixture was diluted with methylene chloride and washed with brine. The organic portion was concentrated in vacuo and the residue purified by flash chromatography on silica gel (methylene chloride:methanol, 95:5+1% ammonium hydroxide) to give the title compound (17 mg).
Reaction SMILES: [CH2:1]([O:8][C:9]1[CH:14]=[CH:13][C:12]([C:15]2[O:16][C:17]3[CH:27]=[C:26]([NH:28][S:29]([CH3:32])(=[O:31])=[O:30])[C:25]([CH:33]4[CH2:35][CH2:34]4)=[CH:24][C:18]=3[C:19]=2[C:20]([O:22][CH3:23])=[O:21])=[CH:11][CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH3:36][O:37][C:38]1[CH:45]=[CH:44][C:41]([CH2:42]Br)=[CH:40][CH:39]=1.C(=O)([O-])[O-].[K+].[K+]>CN(C)C=O>[CH2:1]([O:8][C:9]1[CH:10]=[CH:11][C:12]([C:15]2[O:16][C:17]3[CH:27]=[C:26]([N:28]([CH2:42][C:41]4[CH:44]=[CH:45][C:38]([O:37][CH3:36])=[CH:39][CH:40]=4)[S:29]([CH3:32])(=[O:30])=[O:31])[C:25]([CH:33]4[CH2:35][CH2:34]4)=[CH:24][C:18]=3[C:19]=2[C:20]([O:22][CH3:23])=[O:21])=[CH:13][CH:14]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: COC(=O)c1c(-c2ccc(OCc3ccccc3)cc2)oc2cc(NS(C)(=O)=O)c(C3CC3)cc12
Reactant: COc1ccc(CBr)cc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: COC(=O)c1c(-c2ccc(OCc3ccccc3)cc2)oc2cc(N(Cc3ccc(OC)cc3)S(C)(=O)=O)c(C3CC3)cc12
Yield: 90.2 %

Procedure:
A mixture of Example 18G (4.0 g, 8.14 mmol), 4-methoxybenzyl bromide 2.21 g, 11 mmol) and potassium carbonate (1.35 g, 9.76 mmol) in N,N-dimethylformamide (25 mL) under N2 was heated at 50° C. for 2 hours, cooled and concentrated. The residue was partitioned between ethyl acetate and water. The organic layer was washed with water, saturated brine, dried (MgSO4), filtered and concentrated. The solid was triturated in hexanes and the solid was collected by filtration and dried to give the title compound as a white solid (4.49 g, 90% yield). MS (ESI+) m/z 612 (M+H)+.
Reaction SMILES: Br[C:2]1[CH:11]=[CH:10][CH:9]=[C:8]2[C:3]=1[CH2:4][CH2:5][N:6]1[C:16](=[O:17])[CH2:15][N:14]=[C:13]([C:18]3[S:19][CH:20]=[CH:21][CH:22]=3)[CH:12]=[C:7]12.[CH3:23][N:24](C=O)C>CCOC(C)=O.[C-]#N.[C-]#N.[Zn+2].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>[O:17]=[C:16]1[N:6]2[CH2:5][CH2:4][C:3]3[C:2]([C:23]#[N:24])=[CH:11][CH:10]=[CH:9][C:8]=3[C:7]2=[CH:12][C:13]([C:18]2[S:19][CH:20]=[CH:21][CH:22]=2)=[N:14][CH2:15]1
Reactant: CN(C)C=O
Reactant: O=C1CN=C(c2cccs2)C=C2c3cccc(Br)c3CCN12
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: [C-]#N
Agent: [Zn+2]
Solvent: CCOC(C)=O
Product: N#Cc1cccc2c1CCN1C(=O)CN=C(c3cccs3)C=C21
Temperature: 170 °C
Reaction time: 0.27 h

Procedure:
A microwave flask was charged with 9-bromo-2-(thiophen-2-yl)-7,8-dihydro-[1,4]diazepino[7,1-a]isoquinolin-5(4H)-one (Example 29) (145 mg, 0.39 mmol), Zn(CN)2 (191 mg, 1.63 mmol) and Pd(PPh3)4 (47 mg, 0.041 mmol) in DMF (4 mL) was heated to 170° C. for 18 h. The reaction was allowed to cool to RT, taken up in AcOEt and washed iwth H2O. The org. layer was dried over Na2SO4, filtered and concentrated in vacuo. The crude product was purified by flash chromatography (SiO2, hexane to hexan/AcOEt 1:1) and prep. HPLC (column: RP-C18 sunfire, 5 μm, 100×300 mm; solvent A: H2O+0.1% TFA; solvent B CH3CN; gradient (% B): 10-30% in 16 min; 50 mL/min). The product obtained was passed onto a SPE cartridge to release the free base, and the residue obtained was triturated in heptane/AcOEt to give the title compound (8 mg) as a yellow solid. UPLC-MS: MS 320.2 (M+H+); UPLC rt 0.87 min. 1H NMR (600 MHz, DMSO-d6): δ ppm 3.07 (t, J=5.55 Hz, 2 H); 3.87 (br. s., 2 H); 4.29 (br. s., 2 H); 7.11 (t, J=4.14 Hz, 1 H); 7.51 (s, 1 H); 7.56 (t, J=7.87 Hz, 1 H); 7.66 (d, J=4.24 Hz, 2 H); 7.93 (d, J=7.47 Hz, 1 H); 8.42 (d, J=8.07 Hz, 1 H).
Reaction SMILES: [Cl:1][C:2]1[C:6]([C:7]([O:9][CH2:10][CH3:11])=[O:8])=[C:5](Cl)[S:4][N:3]=1.[CH3:13][C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=1B(O)O.[F-].[K+].C1OCCOCCOCCOCCOCCOC1>CC(=O)OCC.CC([O-])=O.CC([O-])=O.[Pd+2]>[Cl:1][C:2]1[C:6]([C:7]([O:9][CH2:10][CH3:11])=[O:8])=[C:5]([C:15]2[CH:16]=[CH:17][CH:18]=[CH:19][C:14]=2[CH3:13])[S:4][N:3]=1
Reactant: CCOC(=O)c1c(Cl)nsc1Cl
Reactant: Cc1ccccc1B(O)O
Agent: [Pd+2]
Agent: C1COCCOCCOCCOCCOCCO1
Agent: CC(=O)[O-]
Solvent: CCOC(C)=O
Product: CCOC(=O)c1c(Cl)nsc1-c1ccccc1C
Temperature: 110 °C
Reaction time: 8 h

Procedure:
Into a 100-mL round-bottom flask purged and maintained with an inert atmosphere of nitrogen, was placed ethyl 3,5-dichloro-1,2-thiazole-4-carboxylate (1 g, 4.42 mmol, 1.00 equiv), (2-methylphenyl)boronic acid (665 mg, 4.89 mmol, 1.11 equiv), Pd(OAc)2 (49.7 mg, 0.22 mmol, 0.05 equiv), KF (773 mg), 18-Crown-6 (117 mg, 0.44 mmol, 0.10 equiv), Tol (40 mL). The resulting solution was stirred overnight at 110° C. in an oil bath. The resulting solution was diluted with 50 mL of EA. The resulting mixture was washed with 5×30 mL of sodium chloride(aq). The mixture was dried over anhydrous sodium sulfate and concentrated under vacuum. The residue was applied onto a silica gel column with ethyl acetate/petroleum ether (0:100). This resulted in 730 mg (59%) of ethyl 3-chloro-5-(2-methylphenyl)-1,2-thiazole-4-carboxylate as yellow oil.
Reaction SMILES: [OH:1][CH2:2][C:3]1[CH:4]=[CH:5][C:6]2[O:11][CH2:10][C:9](=[O:12])[NH:8][C:7]=2[CH:13]=1.[H-].[Na+].Br[CH2:17][CH2:18][CH2:19][CH2:20][O:21][Si:22]([CH:29]([CH3:31])[CH3:30])([CH:26]([CH3:28])[CH3:27])[CH:23]([CH3:25])[CH3:24].C(=O)([O-])O.[Na+]>CN(C)C=O>[OH:1][CH2:2][C:3]1[CH:4]=[CH:5][C:6]2[O:11][CH2:10][C:9](=[O:12])[N:8]([CH2:17][CH2:18][CH2:19][CH2:20][O:21][Si:22]([CH:26]([CH3:27])[CH3:28])([CH:23]([CH3:25])[CH3:24])[CH:29]([CH3:30])[CH3:31])[C:7]=2[CH:13]=1
Reactant: O=C1COc2ccc(CO)cc2N1
Reactant: CC(C)[Si](OCCCCBr)(C(C)C)C(C)C
Agent: O=C([O-])O
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: CC(C)[Si](OCCCCN1C(=O)COc2ccc(CO)cc21)(C(C)C)C(C)C
Reaction time: 1 h

Procedure:
The stirred solution of 3.70 g of 6-hydroxymethyl-4H-benzo[1,4]oxazin-3-one (Example 2d) and 95 ml of N,N-dimethylformamide is cooled to 0° C., admixed with 0.808 g of sodium hydride (60% dispersion) and stirred over 1 hour. After 7.57 g of (4-bromobutoxy)triisopropylsilane have been added, the mixture is stirred at 0° C. over a further 18 hours and the resulting reaction mixture is poured onto aqueous 1M sodium hydrogencarbonate solution (200 ml). The mixture is extracted with tert-butyl methyl ether (2×200 ml). The organic phases are washed successively with water (3×200 ml) and brine (200 ml), dried over sodium sulphate, filtered and concentrated by evaporation. The title compound is obtained as a slightly yellowish oil from the residue by means of flash chromatography (SiO2 60F). Rf=0.43 (1:1 EtOAc-heptane); Rt=5.86.
Reaction SMILES: N1C2C(=CC=C3C=2N=CC=C3)C=CC=1.N#N.[Br:17][C:18]1[CH:30]=[CH:29][C:28]2[C:27]3[C:22](=[CH:23][C:24]([Br:31])=[CH:25][CH:26]=3)[NH:21][C:20]=2[CH:19]=1.I[C:33]1[CH:38]=[CH:37][C:36]([C:39]([CH3:42])([CH3:41])[CH3:40])=[CH:35][CH:34]=1>C1(C)C=CC=CC=1.[Cu]Cl.O>[C:39]([C:36]1[CH:37]=[CH:38][C:33]([N:21]2[C:22]3[CH:23]=[C:24]([Br:31])[CH:25]=[CH:26][C:27]=3[C:28]3[C:20]2=[CH:19][C:18]([Br:17])=[CH:30][CH:29]=3)=[CH:34][CH:35]=1)([CH3:42])([CH3:41])[CH3:40]
Reactant: Brc1ccc2c(c1)[nH]c1cc(Br)ccc12
Reactant: CC(C)(C)c1ccc(I)cc1
Agent: Cl[Cu]
Agent: N#N
Agent: c1cnc2c(c1)ccc1cccnc12
Solvent: Cc1ccccc1
Solvent: O
Product: CC(C)(C)c1ccc(-n2c3cc(Br)ccc3c3ccc(Br)cc32)cc1
Temperature: 130 °C

Procedure:
A degassed solution of 489.5 mg (0.156%) of copper(I) chloride and 906 mg (1%) mmol) of 1,10-phenanthroline in 100 ml of toluene were saturated with N2 for 1 hour and heated to 130° C. The solution was subsequently admixed with 16.2 g (50 mmol) of 2,7-dibromocarbazole and 13.2 g (50 mmol) of 1-iodo-4-tert-butylbenzene and heated at 180° C. for 2 hours. After cooling, the mixture was admixed with 180 ml of water, the organic phase was separated off and the solvent was removed under reduced pressure. The product was recrystallized from n-hexane. Yield: 13 g (59%). Purity according to HPLC: 99.5%
Reaction SMILES: [CH2:1]([O:4][C:5]([NH:7][C:8]1([C:11]2[CH:19]=[CH:18][C:14]([C:15]([OH:17])=O)=[CH:13][CH:12]=2)[CH2:10][CH2:9]1)=[O:6])[CH:2]=[CH2:3].CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.[O:42]1[C:50]2[C:45](=[CH:46][CH:47]=[CH:48][CH:49]=2)[CH2:44][C:43]1=[O:51].[H-].[Na+]>CN(C=O)C.O.C(O)(=O)C.C(N(CC)CC)C>[CH2:1]([O:4][C:5](=[O:6])[NH:7][C:8]1([C:11]2[CH:12]=[CH:13][C:14]([C:15]([OH:17])=[C:44]3[C:45]4[CH:46]=[CH:47][CH:48]=[CH:49][C:50]=4[O:42][C:43]3=[O:51])=[CH:18][CH:19]=2)[CH2:9][CH2:10]1)[CH:2]=[CH2:3]
Reactant: O=C1Cc2ccccc2O1
Reactant: C=CCOC(=O)NC1(c2ccc(C(=O)O)cc2)CC1
Agent: CN(C)C(On1nnc2ccccc21)=[N+](C)C
Agent: F[B-](F)(F)F
Agent: [H-]
Solvent: CN(C)C=O
Solvent: O
Solvent: CC(=O)O
Product: C=CCOC(=O)NC1(c2ccc(C(O)=C3C(=O)Oc4ccccc43)cc2)CC1
Temperature: 25 °C
Reaction time: 0.25 h

Procedure:
0.8 g of 4-(1-allyloxycarbonylaminocyclopropyl)benzoic acid and 0.585 mL of triethylamine were dissolved in 10 mL of anhydrous DMF and combined with 1.16 g of TBTU, stirred for 15 minutes at RT, then combined with 0.4 g of coumaranone and stirred for a further 10 minutes. While cooling with the ice bath, 0.42 g of NaH was added batchwise as a 60% suspension in white oil, the mixture was stirred for 2 hours at RT and, once the reaction had ended, the mixture was diluted with water to a total volume of approximately 150 mL. The mixture was acidified with 2N acetic acid. The crystals were suction filtered and washed with water. Yield: 1.1 g of solid with a melting point of 125° C.-126° C.
Reaction SMILES: FC(F)(F)C(O)=O.C(O[C:13]([N:15]1[CH2:20][CH2:19][C:18]2[N:21]=[C:22]([C:24]([O:26][CH3:27])=[O:25])[O:23][C:17]=2[CH2:16]1)=O)(C)(C)C>ClCCl>[CH3:27][O:26][C:24]([C:22]1[O:23][C:17]2[CH2:16][N:15]([CH3:13])[CH2:20][CH2:19][C:18]=2[N:21]=1)=[O:25]
Reactant: COC(=O)c1nc2c(o1)CN(C(=O)OC(C)(C)C)CC2
Solvent: ClCCl
Solvent: O=C(O)C(F)(F)F
Product: COC(=O)c1nc2c(o1)CN(C)CC2
Reaction time: 0.17 h
Yield: 74 %

Procedure:
Trifluoroacetic acid (15 ml) was added to a solution of 5-(tert-butoxycarbonyl)-2-methoxycarbonyl-4,5,6,7-tetrahydrooxazolo[5,4-c]pyridine (500 mg) in dichloromethane (15 ml) at room temperature, and the mixture was stirred for 10 minutes. The reaction mixture was concentrated under reduced pressure, and dichloromethane (20 ml), triethylamine (0.495 ml), acetic acid (205 ml), formalin (0.230 ml) and sodium triacetoxyborohydride (570 mg) were added to the resultant residue at room temperature. After stirring for 15 minutes, dichloromethane (20 ml) and a saturated aqueous solution (50 ml) of sodium hydrogencarbonate were added to separate an organic layer. The water layer was extracted with dichloromethane (3×20 ml). After the resultant organic layers were combined and dried over anhydrous sodium sulfate, the solvent was distilled off under reduced pressure. The residue was purified by column chromatography on silica gel (chloroform:methanol=20:1→10:1) to obtain the title compound (257 mg) as a colorless oil.
Reaction SMILES: [F:1][C:2]1[CH:7]=[C:6]([F:8])[C:5]([N+:9]([O-])=O)=[CH:4][C:3]=1[OH:12].[H][H]>CO.[Ni]>[F:1][C:2]1[CH:7]=[C:6]([F:8])[C:5]([NH2:9])=[CH:4][C:3]=1[OH:12]
Reactant: [H][H]
Reactant: O=[N+]([O-])c1cc(O)c(F)cc1F
Agent: [Ni]
Solvent: CO
Product: Nc1cc(O)c(F)cc1F
Yield: 90.5 %

Procedure:
24 g of 2,4-Difluoro-5-nitrophenol, dissolved in 120 ml of methanol, are subjected to hydrogenation at a hydrogen pressure of 20-40 bar at 25°-45° C. in the presence of 2 g of Raney nickel. When constant pressure is reached (i.e. when the take-up of hydrogen is complete), the pressure is released and the mixture is cooled, the solution is free from catalyst by filtration, and the methanol is subsequently removed by distillation at reduced pressure. 18 g (GC purity 97.5%) of 2,4-difluoro-5-amino-phenol are obtained.
Reaction SMILES: [C:1](Cl)(=[O:11])[C:2]1[CH:10]=[CH:9][C:5]([C:6](Cl)=[O:7])=[CH:4][CH:3]=1.[Cl-].[Al+3].[Cl-].[Cl-].Cl.[CH:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1>>[C:1]([C:2]1[CH:10]=[CH:9][C:5]([C:6](=[O:7])[C:2]2[CH:10]=[CH:9][CH:5]=[CH:4][CH:3]=2)=[CH:4][CH:3]=1)(=[O:11])[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1
Reactant: c1ccccc1
Reactant: O=C(Cl)c1ccc(C(=O)Cl)cc1
Agent: Cl
Agent: [Al+3]
Agent: [Cl-]
Product: O=C(c1ccccc1)c1ccc(C(=O)c2ccccc2)cc1

Procedure:
1,4-Dibenzoylbenzene is prepared essentially as described by Noelting and Kohn, Ber. 19, 147 (1886). Terephthaloyl dichloride (20.3 g, 0.1 mole) is dissolved in benzene (350 ml) and anhydrous aluminum chloride (30 g, 0.22 mole) is added. The mixture is heated at 70° for 7 hours, cooled to 20° and maintained at this temperature for eighteen hours with continual stirring. The reaction mixture is then added to 1 l crushed ice and 20 ml 37% hydrochloric acid. The benzene solution is washed three times with water and twice with sodium bicarbonate solution. The excess benzene is removed by distillation. The resulting crystalline material is recrystallized from dimethylformamide, yield 22 g (76% of theory) white crystals mp 158°-159°.