Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [OH:1][C:2]1[CH:11]=[C:10]2[C:5]([C:6](=[O:13])[C:7]([I:12])=[CH:8][O:9]2)=[CH:4][CH:3]=1.Cl[CH2:15][C:16]1[S:20][C:19]([C:21]2[CH:26]=[CH:25][C:24]([C:27]([F:30])([F:29])[F:28])=[CH:23][CH:22]=2)=[N:18][C:17]=1[CH3:31].[I-].[Na+].C(=O)([O-])[O-].[K+].[K+]>CN(C)C=O.O>[I:12][C:7]1[C:6](=[O:13])[C:5]2[C:10](=[CH:11][C:2]([O:1][CH2:15][C:16]3[S:20][C:19]([C:21]4[CH:22]=[CH:23][C:24]([C:27]([F:30])([F:28])[F:29])=[CH:25][CH:26]=4)=[N:18][C:17]=3[CH3:31])=[CH:3][CH:4]=2)[O:9][CH:8]=1
Reactant: Cc1nc(-c2ccc(C(F)(F)F)cc2)sc1CCl
Reactant: O=c1c(I)coc2cc(O)ccc12
Agent: O=C([O-])[O-]
Agent: [I-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: O
Product: Cc1nc(-c2ccc(C(F)(F)F)cc2)sc1COc1ccc2c(=O)c(I)coc2c1
Temperature: 25 °C

Procedure:
A mixture of 7-hydroxy-3-iodochromen-4-one (864 mg, 3.0 mmol), 5-(chloromethyl)-4-methyl-2-(4-(trifluoromethyl)phenyl)thiazole) (875 mg, 3.0 mmol), sodium iodide (450 mg, 3.0 mmol), and potassium carbonate (552 mg, 4.0 mmol) was dissolved in N,N-dimethylformamide (10 ml) at room temperature under nitrogen. The mixture was heated at 600 for 1 hour, cooled to room temperature, and water (30 ml) added to the mixture. The aqueous mixture was extracted with methylene chloride (3×30 ml), and the combined organic layer washed with brine (30 ml), dried over sodium sulfate, and solvent removed from the filtrate under reduced pressure. Crystallization of the crude product from ethyl acetate (4 ml) gave 3-iodo-7-({4-methyl-2-[4-(trifluoromethyl)phenyl](1,3-thiazol-5-yl)}methoxy)chromen-4-one, a compound of formula (6).
Reaction SMILES: [F:1][C:2]1[CH:7]=[C:6]([CH:8]2OC(C)(C)C(C)(C)O2)[CH:5]=[CH:4][C:3]=1[C:17]1[CH:26]=[N:25][C:24]2[NH:23][CH2:22][CH2:21][O:20][C:19]=2[CH:18]=1.Br[C:28]1[CH:33]=[CH:32][CH:31]=C[C:29]=1[S:34]([NH:37][C@@H:38]([CH3:41])[CH2:39][OH:40])(=[O:36])=[O:35]>>[O:20]1[CH2:21][CH2:22][NH:23][C:24]2[N:25]=[CH:26][C:17]([C:3]3[CH:4]=[CH:5][C:6]([C:8]4[C:29]([S:34]([NH:37][C@@H:38]([CH3:41])[CH2:39][OH:40])(=[O:35])=[O:36])=[CH:28][CH:33]=[CH:32][CH:31]=4)=[CH:7][C:2]=3[F:1])=[CH:18][C:19]1=2
Reactant: C[C@@H](CO)NS(=O)(=O)c1ccccc1Br
Reactant: CC1(C)OC(c2ccc(-c3cnc4c(c3)OCCN4)c(F)c2)OC1(C)C
Product: C[C@@H](CO)NS(=O)(=O)c1ccccc1-c1ccc(-c2cnc3c(c2)OCCN3)c(F)c1

Procedure:
The title compound was prepared in a manner similar to that described in Example 444 using 7-(2-fluoro-4-(4,4,5,5-tetramethyl-1,3-dioxolan-2-yl)phenyl)-3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazine and (S)-2-bromo-N-(1-hydroxypropan-2-yl)benzenesulfonamide. MS (ESI): mass calcd. for C22H22FN3O4S, 443.13; m/z found, 444.1 [M+H]+. 1H NMR (400 MHz, CD3OD) δ 8.15-8.12 (m, 1H), 7.80 (m, 1H), 7.72 (d, J=1.3, 1H), 7.69-7.64 (m, 1H), 7.62-7.52 (m, 2H), 7.40-7.33 (m, 3H), 4.37 (t, J=4.6, 2H), 3.76-3.69 (m, 2H), 3.43-3.36 (m, 1H), 3.30-3.26 (m, 1H), 3.24-3.16 (m, 1H), 1.04-1.01 (m, 3H).
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([O:8][C:9]2[N:14]=[CH:13][C:12]([C:15]([O:17]CC)=[O:16])=[CH:11][CH:10]=2)=[CH:4][CH:3]=1.[OH-].[Li+].Cl>O1CCOCC1.O>[F:1][C:2]1[CH:3]=[CH:4][C:5]([O:8][C:9]2[N:14]=[CH:13][C:12]([C:15]([OH:17])=[O:16])=[CH:11][CH:10]=2)=[CH:6][CH:7]=1
Reactant: CCOC(=O)c1ccc(Oc2ccc(F)cc2)nc1
Agent: Cl
Agent: [Li+]
Agent: [OH-]
Solvent: O
Solvent: C1COCCO1
Product: O=C(O)c1ccc(Oc2ccc(F)cc2)nc1
Temperature: 25 °C
Reaction time: 2 h
Yield: 94.8 %

Procedure:
Ethyl 6-[(4-fluorophenyl)oxy]-3-pyridinecarboxylate (D13) (0.275 g, 1.054 mmol) was taken up in 1,4-dioxane (5 mL) and lithium hydroxide (0.050 g, 2.109 mmol) was dissolved in water. The two solutions were combined and stirred at room temperature for 2 h. The mixture was acidified to pH 5 with 2M HCl and concentrated. The residue was taken up in ethyl acetate, dried and concentrated to yield the title compound as a cream/white solid (0.233 g). δH (DMSO-d6, 400 MHz) 13.20 (1H, bs), 8.65 (1H, dd), 8.28 (1H, dd), 7.26 (4H, m), 7.12 (1H, d). MS (ES): MH+ 234.2, (M-H+) 232.1.
Reaction SMILES: [N:1]1([C:5]2[C:10]3=[C:11]([C:15]4[CH:16]=[N:17][N:18]([CH3:20])[CH:19]=4)[N:12]=[C:13]([CH3:14])[N:9]3[N:8]=[CH:7][N:6]=2)[CH2:4][CH2:3][CH2:2]1.[CH3:21][O:22][C:23]1[CH:28]=[CH:27]C(CNC)=[CH:25][CH:24]=1.Cl.N1CCC1>>[CH3:21][O:22][C:23]1[CH:28]=[CH:27][C:3]([CH2:4][N:1]([CH3:2])[C:5]2[C:10]3=[C:11]([C:15]4[CH:16]=[N:17][N:18]([CH3:20])[CH:19]=4)[N:12]=[C:13]([CH3:14])[N:9]3[N:8]=[CH:7][N:6]=2)=[CH:25][CH:24]=1
Reactant: CNCc1ccc(OC)cc1
Reactant: Cc1nc(-c2cnn(C)c2)c2c(N3CCC3)ncnn12
Agent: C1CNC1
Agent: Cl
Product: COc1ccc(CN(C)c2ncnn3c(C)nc(-c4cnn(C)c4)c23)cc1

Procedure:
The product was synthesized in a manner similar to that described for the preparation of 4-(azetidin-1-yl)-7-methyl-5-(1-methyl-1H-pyrazol-4-yl)imidazo[5,1-f][1,2,4]triazine in Example 2, except that 1-(4-methoxyphenyl)-N-methylmethanamine was utilized in place of azetidine hydrochloride, and the workup was modified somewhat: after the slurry was extracted with dichloromethane, the combined organic layers were washed with 1 N aqueous sodium hydroxide solution, washed with saturated aqueous sodium chloride solution, and dried over sodium sulfate. After filtration, the filtrate was concentrated in vacuo and passed through a short column of silica gel (Eluant: 5% methanol in ethyl acetate). The eluant was concentrated under reduced pressure, and the resulting solid was washed with tert-butyl methyl ether followed by diethyl ether, to provide C6. Yield: 36.0 g, 99.1 mmol, 76%. LCMS m/z 364.2 (M+1). 1H NMR (400 MHz, CDCl3) δ 2.67 (s, 3H), 2.84 (s, 3H), 3.77 (s, 3H), 3.88 (s, 3H), 4.66 (s, 2H), 6.82 (br d, J=8.7 Hz, 2H), 7.07 (br d, J=8.6 Hz, 2H), 7.58 (s, 1H), 7.62 (s, 1H), 7.89 (s, 1H).
Reaction SMILES: C(C1N=C(N2CCOCC2)C2N=NN(CC3C=CC=CC=3Cl)C=2N=1)(C)(C)C.[C:28]([C:32]1[N:33]=[C:34](Cl)[C:35]2[N:40]=[N:39][N:38]([CH2:41][C:42]3[CH:47]=[CH:46][CH:45]=[CH:44][C:43]=3[Cl:48])[C:36]=2[N:37]=1)([CH3:31])([CH3:30])[CH3:29].Cl.[F:51][C:52]1([F:58])[CH2:56][NH:55][CH2:54][C@H:53]1[OH:57]>>[C:28]([C:32]1[N:33]=[C:34]([N:55]2[CH2:56][C:52]([F:58])([F:51])[C@H:53]([OH:57])[CH2:54]2)[C:35]2[N:40]=[N:39][N:38]([CH2:41][C:42]3[CH:47]=[CH:46][CH:45]=[CH:44][C:43]=3[Cl:48])[C:36]=2[N:37]=1)([CH3:31])([CH3:30])[CH3:29]
Reactant: CC(C)(C)c1nc(Cl)c2nnn(Cc3ccccc3Cl)c2n1
Reactant: O[C@@H]1CNCC1(F)F
Agent: CC(C)(C)c1nc(N2CCOCC2)c2nnn(Cc3ccccc3Cl)c2n1
Agent: Cl
Product: CC(C)(C)c1nc(N2C[C@@H](O)C(F)(F)C2)c2nnn(Cc3ccccc3Cl)c2n1

Procedure:
In analogy to the procedure described for the synthesis of 5-tert-butyl-3-(2-chlorobenzyl)-7-morpholin-4-yl-3H-[1,2,3]triazolo[4,5-d]pyrimidine (example 1, step c), the title compound was prepared from 5-tert-butyl-7-chloro-3-(2-chlorobenzyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine and (R)-4,4-difluoropyrrolidin-3-ol hydrochloride and isolated as white solid. MS (m/e): 423.3 (MH+).
Reaction SMILES: [CH3:1][C:2]([O:4][Na])=[O:3].[CH3:6][O:7][C:8]1[CH:13]=[CH:12][C:11]([O:14][CH3:15])=[CH:10][C:9]=1C(=O)C.OO.C([O-])([O-])=O.[K+].[K+]>C(O)(=O)C.CCOCC.O>[C:2]([O:4][C:12]1[CH:13]=[C:8]([O:7][CH3:6])[CH:9]=[CH:10][C:11]=1[O:14][CH3:15])(=[O:3])[CH3:1]
Reactant: COc1ccc(OC)c(C(C)=O)c1
Reactant: CC(=O)O[Na]
Agent: O=C([O-])[O-]
Agent: OO
Agent: [K+]
Solvent: O
Solvent: CCOCC
Solvent: CC(=O)O
Product: COc1ccc(OC)c(OC(C)=O)c1
Temperature: 40 °C
Reaction time: 144 h
Yield: 787.2 %

Procedure:
CH3COONa (0.7 g, 0.009 mol) was added under stirring to a solution of 2′,5′-dimethoxyacetophenone (CAS 1201-38-3, 45 g, 0.25 mol) in acetic acid (50 mL). A 50% solution of H2O2 in H2O (43 g, 0.62 mol) was added dropwise at 40° C. The reaction mixture was stirred at 40° C. for 144 h. Then it was cooled, diluted with ether (150 mL) and H2O (100 mL), and alkalized to pH 6 with a saturated solution of K2CO3. The layers were separated. The organic one was washed with water (2×100 mL), brine, dried, and evaporated. The residue was recrystallized from ether to give the title compound (13.9 g, 28%) as white crystals. LCMS data: 197.0 (M+H)+ and 155.1, 156.1 (M-Ac+H) (calculated for C10H12O4 196.2). 1H NMR data (DMSO-d6): 7.04 (d, 1H, J=9.0 Hz, Ar—H), 6.80 (dd, 1H, J1=3.2 Hz, J2=9.0 Hz, Ar—H), 6.72 (d, 1H, J=2.9 Hz, Ar—H), 3.70 (s, 3H, —OCH3), 3.69 (s, 3H, —OCH3), 2.24 (s, 3H, —COCH3).
Reaction SMILES: [C:1]([C:5]1[CH:17]=[CH:16][CH:15]=[C:14]2[C:6]=1[C:7]1[C:8](=[O:28])[CH2:9][CH:10]([C:18]3[CH:23]=[CH:22][C:21]([C:24]([F:27])([F:26])[F:25])=[CH:20][CH:19]=3)[CH2:11][C:12]=1[NH:13]2)([O:3][CH3:4])=[O:2].[CH2:29](Br)[C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1.C(=O)([O-])[O-].[K+].[K+]>CN(C=O)C.CCOC(C)=O.Cl>[C:30]1([CH2:29][N:13]2[C:12]3[CH2:11][CH:10]([C:18]4[CH:23]=[CH:22][C:21]([C:24]([F:27])([F:26])[F:25])=[CH:20][CH:19]=4)[CH2:9][C:8](=[O:28])[C:7]=3[C:6]3[C:14]2=[CH:15][CH:16]=[CH:17][C:5]=3[C:1]([O:3][CH3:4])=[O:2])[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1
Reactant: COC(=O)c1cccc2[nH]c3c(c12)C(=O)CC(c1ccc(C(F)(F)F)cc1)C3
Reactant: BrCc1ccccc1
Agent: Cl
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CCOC(C)=O
Solvent: CN(C)C=O
Product: COC(=O)c1cccc2c1c1c(n2Cc2ccccc2)CC(c2ccc(C(F)(F)F)cc2)CC1=O
Temperature: 25 °C
Reaction time: 22 h
Yield: 96 %

Procedure:
A suspension of 5-carbomethoxy-1,2-dihydro-2-(4-trifluoromethylphenyl)-9H-carbazol-4(3H)-one (1.57 g, 4.05 mM), benzyl bromide (0.49 ml, 4.13 mM), and potassium carbonate (1.12 g, 8.10 mM) in 20 mL DMF was stirred at room temperature for 22 hours. The mixture was diluted with EtOAc and 1N HCl. The layers were separated and the aqueous extracted with EtOAc. The combined EtOAc layers were extracted with 1N HCl, water, then brine. After drying (NaSO4), evaporation in vacuo afforded 1.87 g (96%) of the 9-[(phenyl)methyl]-5-carbomethoxy-2-(4-trifluoromethylphenyl)-1,2-dihydrocarbazol-4(3H)-one. 1H NMR (CDCl3) δ7.6 (d, J=8 Hz, 2H), 7.45-7.25 (m, 8H), 6.95 (m, 2H), 5.35 (s, 2H), 4.05 (s, 3H), 3.65 (m, 1H), 3.2 (dd, J=16 and 5 Hz, 1H), 3.0 (dd, J=16 and 10 Hz, 1H), 2.8 (m, 2H). MS (ES) m/e 478.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:32]=[CH:31][C:6]([CH2:7][N:8]([CH2:22][C:23]2[CH:28]=[CH:27][C:26]([O:29][CH3:30])=[CH:25][CH:24]=2)[C:9]2[CH:14]=[C:13]([F:15])[C:12]([C:16]([CH3:20])([CH3:19])[CH2:17][OH:18])=[C:11]([F:21])[CH:10]=2)=[CH:5][CH:4]=1.I[CH3:34].[H-].[Na+].O>CN(C=O)C>[F:21][C:11]1[CH:10]=[C:9]([CH:14]=[C:13]([F:15])[C:12]=1[C:16]([CH3:20])([CH3:19])[CH2:17][O:18][CH3:34])[N:8]([CH2:7][C:6]1[CH:5]=[CH:4][C:3]([O:2][CH3:1])=[CH:32][CH:31]=1)[CH2:22][C:23]1[CH:24]=[CH:25][C:26]([O:29][CH3:30])=[CH:27][CH:28]=1
Reactant: COc1ccc(CN(Cc2ccc(OC)cc2)c2cc(F)c(C(C)(C)CO)c(F)c2)cc1
Reactant: CI
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: O
Product: COCC(C)(C)c1c(F)cc(N(Cc2ccc(OC)cc2)Cc2ccc(OC)cc2)cc1F
Temperature: 0 °C
Reaction time: 4 h
Yield: 73.9 %

Procedure:
To a solution of 2-(4-(bis(4-methoxybenzyl)amino)-2,6-difluorophenyl)-2-methylpropan-1-ol (1.31 g, 2.97 mmol) and iodomethane (0.278 mL, 4.45 mmol) in DMF (10 mL) was added sodium hydride (60%, oil, 0.154 g, 3.86 mmol) at 0° C., and the mixture was stirred at 0° C. for 4 hr. To the reaction mixture was added water, and the mixture was extracted with ethyl acetate. The organic layer was washed with brine, and dried over magnesium sulfate, and the solvent was evaporated under reduced pressure. The obtained residue was purified by silica gel column chromatography (solvent gradient; 3→40% ethyl acetate/hexane) to give 3,5-difluoro-4-(1-methoxy-2-methylpropan-2-yl)-N,N-bis(4-methoxybenzyl)aniline (1.000 g, 2.195 mmol, 74.0%) a yellow oil.
Reaction SMILES: [NH2:1][C@@:2]([C@H:11]1[CH2:15][O:14][CH2:13][C@@H:12]1[S:16][CH2:17][C:18]#[N:19])([C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=1[F:10])[CH3:3].C[Al](C)C>C1(C)C=CC=CC=1>[F:10][C:5]1[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=1[C@:2]1([CH3:3])[C@@H:11]2[C@H:12]([CH2:13][O:14][CH2:15]2)[S:16][CH2:17][C:18]([NH2:19])=[N:1]1
Reactant: C[C@@](N)(c1ccccc1F)[C@H]1COC[C@@H]1SCC#N
Agent: C[Al](C)C
Solvent: Cc1ccccc1
Product: C[C@]1(c2ccccc2F)N=C(N)CS[C@H]2COC[C@@H]21
Temperature: 60 °C
Reaction time: 2 h
Yield: 43.5 %

Procedure:
A solution of the {rel-(3R,4S)-4-[(S)-1-amino-1-(2-fluoro-phenyl)-ethyl]-tetrahydro-furan-3-ylsulfanyl}-acetonitrile (460 mg, 1.64 mmol) in toluene (6 ml) was treated dropwise with trimethylaluminum (902 μl, 1.8 mmol) at room temperature. The reaction mixture was stirred at 60° C. for 2 hours, thereafter, extracted with a mixture of a saturated solution of sodium hydrogencarbonate and ethyl acetate. The combined organic layers were dried over sodium sulphate and evaporated at reduced pressure. The residue was purified by flash chromatography on silica gel using a mixture of ethyl acetate, methanol, ammonium hydroxide=100:10:1 as the eluent. The (3aR,8S,8aS)-rel-8-(2-fluoro-phenyl)-8-methyl-1,3,3a,5,8,8a-hexahydro-2-oxa-4-thia-7-aza-azulen-6-ylamine (200 mg, 43% yield) was obtained as a light yellow oil. MS (ISP): m/z=281.0 [M+H]+.
Reaction SMILES: [C:1]([C:3]1[CH:4]=[C:5]([CH:10]=[CH:11][C:12]=1[CH3:13])[C:6]([O:8][CH3:9])=[O:7])#[N:2].C1C(=O)N([Br:21])C(=O)C1>C(Cl)(Cl)(Cl)Cl.[W]>[C:1]([C:3]1[CH:4]=[C:5]([CH:10]=[CH:11][C:12]=1[CH2:13][Br:21])[C:6]([O:8][CH3:9])=[O:7])#[N:2]
Reactant: O=C1CCC(=O)N1Br
Reactant: COC(=O)c1ccc(C)c(C#N)c1
Agent: [W]
Solvent: ClC(Cl)(Cl)Cl
Product: COC(=O)c1ccc(CBr)c(C#N)c1
Yield: 48.2 %

Procedure:
A mixture of methyl 3-cyano-4-methylbenzoate (1.78 g, 9.79 mmol) and NBS (1.92 g, 10.8 mmol) in CCl4 (150 mL) was irradiated with a 150W tungsten lamp at 50° C. for 2 h. The reaction was cooled, filtered, and concentrated. The residue was chromatographed (250 g silica, 10% EtOAc/hexanes to 15% EtOAc/hexanes) to give the title compound (1.20 g, 48%); IR(CHCl3: 1291, 1302, 1439, 1728 cm−1; NMR(300 MHz, CDCl3): 4.01 (s, 3H); 4.67 (s, 3H); 7.66 (d, 1H, J=8.1 Hz); 8.24 (d, 1H, J=8.7 Hz); 8.34 (s, 1H); MS(FD): 253.0.
Reaction SMILES: [Cl:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]([OH:8])=O)=[CH:4][CH:3]=1.[C:11]1([CH:17]2[C:26]3[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=3)[NH:20][C:19](=[O:27])[CH2:18]2)[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1>>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([C:6]([C:24]2[CH:25]=[C:26]3[C:21](=[CH:22][CH:23]=2)[NH:20][C:19](=[O:27])[CH2:18][CH:17]3[C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)=[O:8])=[CH:9][CH:10]=1
Reactant: O=C(O)c1ccc(Cl)cc1
Reactant: O=C1CC(c2ccccc2)c2ccccc2N1
Product: O=C1CC(c2ccccc2)c2cc(C(=O)c3ccc(Cl)cc3)ccc2N1
Temperature: 0 °C
Yield: 50.8 %

Procedure:
4-Chlorobenzoic acid (21.23 g) and 3,4-dihydro-4-phenyl-2(1H)-quinolinone (15 g) were heated in polyphosphoric acid (150 g) at 140° C. for 24 hours. The mixture was poured into ice water and filtered off. The precipitate was taken up in DCM. The organic layer was washed with NaHCO3 (10%) and water, dried (MgSO4) and evaporated. The residue was crystallized from 2-propanone, yielding 12.34 g (50%) of (±)-6-(4-chlorobenzoyl)-3,4-dihydro-4-phenyl-2(1H)-quinolinone; mp. 204° C. (interm. 2-a).
Reaction SMILES: [CH3:1][N:2]([N:12]1[CH:16]=[CH:15][CH:14]=[CH:13]1)[C:3]1[CH:8]=[CH:7][N:6]=[CH:5][C:4]=1[N+:9]([O-])=O.C(O)(C)C>[Pd].CO>[CH3:1][N:2]([C:3]1[CH:8]=[CH:7][N:6]=[CH:5][C:4]=1[NH2:9])[N:12]1[CH:13]=[CH:14][CH:15]=[CH:16]1
Reactant: CN(c1ccncc1[N+](=O)[O-])n1cccc1
Agent: [Pd]
Solvent: CO
Solvent: CC(C)O
Product: CN(c1ccncc1N)n1cccc1
Temperature: 25 °C
Reaction time: 18 h

Procedure:
In a Parr shaker apparatus was placed a mixture prepared from 5.0 g of N-methyl-N-(1H-pyrrol-1-yl)-3-nitro-4-pyridinamine, 310 mg of 10% palladium on carbon, 175 ml of isopropanol and 30 ml of methanol. This was shaken for 18 hours at ambient temperature.
Reaction SMILES: Br[C:2]1[CH:10]=[CH:9][C:5]2[N:6]=[CH:7][NH:8][C:4]=2[CH:3]=1.[CH3:11][O:12][C:13]1[CH:14]=[C:15]([CH:18]=[CH:19][C:20]=1[O:21][CH3:22])[CH2:16][NH2:17].C1(P(C2CCCCC2)C2C=CC=CC=2C2C=CC=CC=2N(C)C)CCCCC1.C[Si]([N-][Si](C)(C)C)(C)C.[Li+].C1COCC1>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.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[CH3:11][O:12][C:13]1[CH:14]=[C:15]([CH:18]=[CH:19][C:20]=1[O:21][CH3:22])[CH2:16][NH:17][C:2]1[CH:10]=[CH:9][C:5]2[N:6]=[CH:7][NH:8][C:4]=2[CH:3]=1
Reactant: Brc1ccc2nc[nH]c2c1
Reactant: COc1ccc(CN)cc1OC
Agent: [Pd]
Agent: CN(C)c1ccccc1-c1ccccc1P(C1CCCCC1)C1CCCCC1
Agent: C[Si](C)(C)[N-][Si](C)(C)C
Solvent: C1CCOC1
Product: COc1ccc(CNc2ccc3nc[nH]c3c2)cc1OC

Procedure:
The compound was synthesized starting from 5-bromobenzimidazole (200 mg; 1 mmol; 1 eq.), 3,4-dimethoxybenzylamine (201 mg; 0.181 ml; 1.2 mmol; 1.2 eq.), 2-dicyclohexylphosphino-2′-(N,N-dimethylamino)biphenyl (9 mg; 0.024 mmol; 0.024 eq.; 2.4 mol %), Pd2 dba3 (9 mg; 0.01 mmol; 0.01 eq.; 1 mol %) and lithiumbis(trimethylsilyl)amide 1 M in THF (2.2 ml; 2.2 mmol; 2.2 eq.) according to method 1; Yield: 0.064 g (22.6%); MS m/z: 284.1 [M+H]+; 1H-NMR (500 MHz, DMSO d6): δ 3.69 (s, 3H); 3.71 (s, 3H); 4.17 (d, 2H, 3J=5.8 Hz); 5.96 (br s, 1H); 6.48 (br s, 1H); 6.58-6.60 (m, 1H); 6.85-6.89 (m, 2H); 6.99 (s, 1H); 7.27-7.29 (m, 1H); 7.80 (s, 1H); 11.78 (br s, 1H); HPLC (METHOD [A]): rt 8.92 min (100%)
Reaction SMILES: [N+:1]([C:4]1[CH:5]=[C:6]2[C:10](=[CH:11][CH:12]=1)[N:9]([CH2:13][C:14]1[CH:19]=[CH:18][CH:17]=[C:16]([F:20])[CH:15]=1)[N:8]=[CH:7]2)([O-])=O>C(O)(=O)C.CCOC(C)=O.[Fe]>[NH2:1][C:4]1[CH:5]=[C:6]2[C:10](=[CH:11][CH:12]=1)[N:9]([CH2:13][C:14]1[CH:19]=[CH:18][CH:17]=[C:16]([F:20])[CH:15]=1)[N:8]=[CH:7]2
Reactant: O=[N+]([O-])c1ccc2c(cnn2Cc2cccc(F)c2)c1
Agent: [Fe]
Solvent: CCOC(C)=O
Solvent: CC(=O)O
Product: Nc1ccc2c(cnn2Cc2cccc(F)c2)c1
Yield: 75.8 %

Procedure:
5-nitro-1-N-(3-fluorobenzyl)indazole (7.9 g, 29.1 mmol, 1 equiv) and iron (8.13 g, 145.6 mmol, 5 equiv) were mixed in 200 mL acetic acid and 50 mL EtOAc, and were stirred at rt for 36 h. The reaction mixture was filtered through a pad of Celite®. The filtrate was concentrated in vacuo to 10 mL volume. The contents were diluted with water (10 mL) and neutralized with saturated Na2CO3 solution. The solution was extracted with EtOAc (3×500 mL), the combined organic layers dried over MgSO4, filtered, and concentrated in vacuo. The resulting crude material was purified by column chromatography eluting with hexanes/EtOAC (4:1 to 3:1) to give 5-amino-1-N-(3-fluorobenzyl)indazole (5.32 g, 76%) as a light brown solid. 1H-NMR (DMSO-d6) δ 7.72 (s, 1H), 7.22-7.36 (m, 2H), 6.87-7.05 (m, 3H), 6.70-6.77 (m, 2H), 5.48 (s, 2H), 4.78 (br s, 2H); LCMS RT=1.66 min; [M+H]+=242.2.
Reaction SMILES: [CH:1]1[C:11]2[C:10]3[CH:12]=[CH:13][CH:14]=[CH:15][C:9]=3[CH2:8][N:7]([C:16](=[NH:20])[O:17][CH2:18][CH3:19])[CH2:6][C:5]=2[CH:4]=[CH:3][CH:2]=1.[F:21][C:22]1[CH:30]=[CH:29][CH:28]=[C:27]([F:31])[C:23]=1[C:24](Cl)=[O:25]>>[F:21][C:22]1[CH:30]=[CH:29][CH:28]=[C:27]([F:31])[C:23]=1[C:24]([N:20]=[C:16]([N:7]1[CH2:6][C:5]2[CH:4]=[CH:3][CH:2]=[CH:1][C:11]=2[C:10]2[CH:12]=[CH:13][CH:14]=[CH:15][C:9]=2[CH2:8]1)[O:17][CH2:18][CH3:19])=[O:25]
Reactant: CCOC(=N)N1Cc2ccccc2-c2ccccc2C1
Reactant: O=C(Cl)c1c(F)cccc1F
Product: CCOC(=NC(=O)c1c(F)cccc1F)N1Cc2ccccc2-c2ccccc2C1

Procedure:
starting from ethyl 5,7-dihydro-6H-dibenz[c,e]azepine-6-carboximidate and 2,6-difluorobenzoyl chloride, there is obtained ethyl N-(2,6-difluorobenzoyl)-5,7-dihydro-6H-dibenz[c,e]azepine-6-carboximidate as a resin, mass spectrum m/e: M+ 406 (5), 377 (21), 194 (100), 141 (42);
Reaction SMILES: [C:1]([CH2:4][N:5]1[CH2:16][CH2:15][NH:14][CH2:13][CH2:12][N:11]([CH2:17][C:18]([OH:20])=[O:19])[CH2:10][CH2:9][N:8]([CH2:21][C:22]([OH:24])=[O:23])[CH2:7][CH2:6]1)([OH:3])=[O:2].[C:25](=O)([O-])[O-].[K+].[K+].CI.Cl.CO.CC(C)=O>CO>[CH3:25][N:14]1[CH2:13][CH2:12][N:11]([CH2:17][C:18]([OH:20])=[O:19])[CH2:10][CH2:9][N:8]([CH2:21][C:22]([OH:24])=[O:23])[CH2:7][CH2:6][N:5]([CH2:4][C:1]([OH:3])=[O:2])[CH2:16][CH2:15]1
Reactant: O=C([O-])[O-]
Reactant: O=C(O)CN1CCNCCN(CC(=O)O)CCN(CC(=O)O)CC1
Agent: Cl
Agent: [K+]
Solvent: CO
Solvent: CI
Solvent: CC(C)=O
Product: CN1CCN(CC(=O)O)CCN(CC(=O)O)CCN(CC(=O)O)CC1
Reaction time: 15 h

Procedure:
To a solution of 250 mg (0.723 mmol) of 1,4,7-triscarboxymethyl-1,4,7,10-tetraazacyclododecane in 2.9 ml of methanol was added 220 mg (1.59 mmol) of potassium carbonate. To the resulting mixture was added 308 mg (2.17 mmol, 3 equiv) of methyl iodide. Within a short time, most of the solids dissolved. After 15 hours at 21° C., a mass of crystals had separated. Additional methanol was added (2 ml) to dissolve the solid. After 23 hours, an additional 102 mg (0.72 mmol) of methyl iodide was added. After an additional 16 hours, the solution was acidified with concentrated hydrochloric acid and the volatiles were removed on the rotary evaporator. The residue was extracted with methanol, filtered, and the methanol evaporated. The residue was crystallized twice from methanol/acetone yielding 56 mg (0.16 mmol) of a colorless solid, melting point 215-240° (dec.). 13C NMR (D2O, ppm vs TMS): 177.2, 171.1, 57.2, 56.5, 54.1, 52.6, 50.1, 49.9, 43.7. Mass spectrum (FAB): m/e 359 (M-H) and 361 (M+H).
Reaction SMILES: [NH2:1][CH:2]([CH2:6][CH3:7])[C:3]([OH:5])=[O:4].Cl[Si](C)(C)C.C(N(C(C)C)CC)(C)C.[Cl:22][C:23]1[CH:31]=[CH:30][CH:29]=[CH:28][C:24]=1[C:25](Cl)=[O:26]>ClCCl>[Cl:22][C:23]1[CH:31]=[CH:30][CH:29]=[CH:28][C:24]=1[C:25]([NH:1][CH:2]([CH2:6][CH3:7])[C:3]([OH:5])=[O:4])=[O:26]
Reactant: CCC(N)C(=O)O
Reactant: O=C(Cl)c1ccccc1Cl
Agent: C[Si](C)(C)Cl
Solvent: ClCCl
Solvent: CCN(C(C)C)C(C)C
Product: CCC(NC(=O)c1ccccc1Cl)C(=O)O
Temperature: 25 °C
Yield: 81.4 %

Procedure:
This compound was prepared according to the procedures described in Int. J. Peptide Protein Res. 1989, 33, 353, and J. Chem. Soc., Chem. Commun. 1995, 2335. 2-Amino-butyric acid (3.87 g, 37.5 mmol) was suspended in 90 mL of dichloromethane, and treated with chloro-trimethyl-silane (9.6 mL, 75 mmol). The mixture was refluxed for 1 h and cooled in an ice bath. Diisopropylethylamine (11.3 mL, 65 mmol) and 2-chloro-benzoyl chloride (4.3 mL, 35.6 mmol) were added. The solution was stirred with cooling for 20 min and then warmed up to room temperature for 1.5 h. The mixture was concentrated and then distributed between ether and diluted NaHCO3 solution. The phases were separated. The aqueous layer was extracted with ether and the ether layer was back washed with water. The combined aqueous layers were acidified to pH 2 with 1N HCl and extracted with ethyl acetate three times. The combined ethyl acetate layers were dried over sodium sulfate, filtered and concentrated to give 2-(2-chloro-benzoylamino)-butyric acid as an off-white solid (7.0 g, 77% yield), which was used directly in the next step without further purification. LCMS calcd for C11H12ClNO3 (m/e) 241, obsd 242 (M+H).
Reaction SMILES: [CH2:1]([C:4]1[C:13]([O:14][Si:15]([CH3:18])([CH3:17])[CH3:16])=[C:12]2[C:7]([CH:8]=[CH:9][CH:10]=[N:11]2)=[CH:6][CH:5]=1)[CH:2]=[CH2:3].[CH3:19][O:20][SiH:21]([O:24][CH3:25])[O:22][CH3:23].[SiH4]>[Pt]>[CH3:19][O:20][Si:21]([CH2:3][CH2:2][CH2:1][C:4]1[C:13]([O:14][Si:15]([CH3:18])([CH3:17])[CH3:16])=[C:12]2[C:7]([CH:8]=[CH:9][CH:10]=[N:11]2)=[CH:6][CH:5]=1)([O:24][CH3:25])[O:22][CH3:23]
Reactant: C=CCc1ccc2cccnc2c1O[Si](C)(C)C
Reactant: CO[SiH](OC)OC
Agent: [Pt]
Agent: [SiH4]
Product: CO[Si](CCCc1ccc2cccnc2c1O[Si](C)(C)C)(OC)OC
Temperature: 40 °C
Reaction time: 72 h

Procedure:
To a one-ounce glass vial containing 6.7 gms (0.026 moles) of 7-allyl-8-trimethylsiloxyquinoline was added 6.34 gms (0.052 moles) of trimethoxysilane and a trace of platinum catalyst (H2PtCl6 4H2O). Some bubbling occurred. The reaction was warmed at 40° C. for 8 hours during which time the reaction was monitored by GLC. A GLC after 3 days at 40° C. showed a small amount of the starting silane and a large product peak corresponding to ##STR17## Analysis showed nd25 =1.525. Infra-red analysis showed the disappearance of the C=C peak. H'NMR: