Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Na].[C:2]([C:4]1[CH:5]=[C:6]([OH:10])[CH:7]=[CH:8][CH:9]=1)#[CH:3].C[O-].[Na+].[N+]([C:17]1[CH:18]=[C:19]2[C:24](=[O:25])[N:23]([C:26]3[CH:31]=[CH:30][CH:29]=[C:28]([C:32]#[CH:33])[CH:27]=3)[C:21](=[O:22])[C:20]2=[CH:34][CH:35]=1)([O-])=O.S(=O)(=O)(O)O>C(Cl)Cl.CCCCCC.CN(C)C(=O)C>[C:2]([C:4]1[CH:5]=[C:6]([CH:7]=[CH:8][CH:9]=1)[O:10][C:17]1[CH:18]=[C:19]2[C:24](=[O:25])[N:23]([C:26]3[CH:31]=[CH:30][CH:29]=[C:28]([C:32]#[CH:33])[CH:27]=3)[C:21](=[O:22])[C:20]2=[CH:34][CH:35]=1)#[CH:3]
Reactant: C#Cc1cccc(O)c1
Reactant: C#Cc1cccc(N2C(=O)c3ccc([N+](=O)[O-])cc3C2=O)c1
Agent: C[O-]
Agent: O=S(=O)(O)O
Agent: [Na+]
Solvent: ClCCl
Solvent: CCCCCC
Solvent: CC(=O)N(C)C
Product: C#Cc1cccc(Oc2ccc3c(c2)C(=O)N(c2cccc(C#C)c2)C3=O)c1
Temperature: 70 °C
Reaction time: 3 h
Yield: 44 %

Procedure:
To the sodium salt of 3-ethynylphenol, prepared from 4.3 g (0.037 mole) of sodium methoxide was added 50 ml of dry N,N-dimethylacetamide, under nitrogen. The mixture was heated to 70° C. and 12.0 g (0.041 mole) of 4-nitro-N-(3-ethynylphenyl)-phthalimide was added. The dark mixture was stirred at 70° C. for 3 hours, then poured into 1.5 liters of ice water. About 100 ml of 1 N sulfuric acid was added to the cold mixture to precipitate the product. The precipitate was collected by filtration, air dried, dissolved in 100 ml of methylene chloride, than again filtered. Chromotography of the filtrate on silica gel using 1:1 hexane:methylene chloride as the eluent gave 5.8 g (44% yield) of product, m.p. 150°-160° C.
Reaction SMILES: Cl[C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([O:8][CH3:9])[N:3]=1.[Cl-].[NH4+].C(O[CH2:15][CH3:16])C>[Ni](Cl)Cl.C1(P(C2C=CC=CC=2)CCCP(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[CH3:9][O:8][C:4]1[CH:5]=[CH:6][CH:7]=[C:2]([C:16]2[CH:15]=[CH:7][CH:6]=[CH:5][CH:4]=2)[N:3]=1
Reactant: COc1cccc(Cl)n1
Reactant: CCOCC
Agent: Cl[Ni]Cl
Agent: [Cl-]
Agent: [NH4+]
Product: COc1cccc(-c2ccccc2)n1

Procedure:
An ether (30 ml) solution of phenyl magnesium bromide ether solution (12.3 ml, 3.0 M, 37.0 mmol) was dropwise added to a mixture of 2-chloro-6-methoxypyridine (4.4 ml, 37.0 mmol), 1,3-bis(diphenylphosphino)propane nickel (II) chloride (228 mg) and diethyl ether (40 ml) at room temperature while 30 minutes. Thereafter, this reaction mixture was stirred under reflux for 1 hour, then the mixture was poured into an aqueous ammonium chloride solution, an organic layer was separated, furthermore an aqueous layer was extracted with dichloromethane. The organic layer was combined, and the solvent was distilled off, and the residue was filtered through a silica gel, thereby obtaining 7.0 g of crude 2-methoxy-6-phenylpyridine as pale yellow oil.
Reaction SMILES: [CH2:1]([C@@H:8]([CH2:12][CH2:13][C@H:14]([CH2:34][C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1)[C:15]([NH:17][C@H:18]1[CH2:24][CH2:23][S:22][C@H:21]2[CH2:25][CH2:26][CH2:27][C@@H:28]([C:29]([O:31][CH3:32])=[O:30])[N:20]2[C:19]1=[O:33])=[O:16])[C:9](O)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[NH2:41][C@@H:42]1[CH2:48][CH2:47][S:46][C@@H:45]2[CH2:49][CH2:50][CH2:51][C@@H:52]([C:53]([O:55][CH3:56])=[O:54])[N:44]2[C:43]1=[O:57]>>[CH2:1]([C@@H:8]([CH2:12][CH2:13][C@H:14]([CH2:34][C:35]1[CH:36]=[CH:37][CH:38]=[CH:39][CH:40]=1)[C:15]([NH:17][C@@H:18]1[CH2:24][CH2:23][S:22][C@@H:21]2[CH2:25][CH2:26][CH2:27][C@@H:28]([C:29]([O:31][CH3:32])=[O:30])[N:20]2[C:19]1=[O:33])=[O:16])[C:9]([NH:41][C@H:42]1[CH2:48][CH2:47][S:46][C@H:45]2[CH2:49][CH2:50][CH2:51][C@@H:52]([C:53]([O:55][CH3:56])=[O:54])[N:44]2[C:43]1=[O:57])=[O:10])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: COC(=O)[C@@H]1CCC[C@H]2SCC[C@@H](N)C(=O)N21
Reactant: COC(=O)[C@@H]1CCC[C@@H]2SCC[C@H](NC(=O)[C@H](CC[C@H](Cc3ccccc3)C(=O)O)Cc3ccccc3)C(=O)N21
Product: COC(=O)[C@@H]1CCC[C@@H]2SCC[C@H](NC(=O)[C@H](CC[C@H](Cc3ccccc3)C(=O)N[C@@H]3CCS[C@@H]4CCC[C@@H](C(=O)OC)N4C3=O)Cc3ccccc3)C(=O)N21

Procedure:
(4S,7S,10aS)-Methyl 4-((2R,5R)-2,5-dibenzyl-6-((4R,7S,10aR)-7-(methoxycarbonyl)-5-oxooctahydro-2H-pyrido[2,1-b][1,3]thiazepin-4-ylamino)-6-oxohexanamido)-5-oxooctahydro-2H-pyrido[2,1-b][1,3]thiazepine-7-carboxylate was synthesized as described in General Procedure H using Intermediate 23 (5.0 mg, 0.0088 mmol) and (4R,7S,10aR)-methyl 4-amino-5-oxooctahydro-2H-pyrido[2,1-b][1,3]thiazepine-7-carboxylate (2.2 mg, 0.0097 mmol) to give a white solid (3.2 mg, 40% yield). Anal. Calcd. for C42H54N4O8S2 m/z 806.4. found: 807.4 (M+H)+.
Reaction SMILES: Cl.[Cl:2][C:3]1[CH:4]=[C:5]([C:10](=[N:24][O:25][CH2:26][CH3:27])[CH:11]2[CH:16]3[CH:12]2[CH2:13][N:14](C(OC(C)(C)C)=O)[CH2:15]3)[CH:6]=[CH:7][C:8]=1[Cl:9].CCCCCC>C(Cl)Cl>[ClH:2].[CH2:26]([O:25][N:24]=[C:10]([CH:11]1[CH:16]2[CH:12]1[CH2:13][NH:14][CH2:15]2)[C:5]1[CH:6]=[CH:7][C:8]([Cl:9])=[C:3]([Cl:2])[CH:4]=1)[CH3:27]
Reactant: CCON=C(c1ccc(Cl)c(Cl)c1)C1C2CN(C(=O)OC(C)(C)C)CC21
Agent: Cl
Solvent: ClCCl
Solvent: CCCCCC
Product: CCON=C(c1ccc(Cl)c(Cl)c1)C1C2CNCC21
Yield: 200.5 %

Procedure:
HCl (g) was bubbled through a solution of tert-butyl 6-((3,4-dichlorophenyl)(ethoxyimino)methyl)-3-azabicyclo[3.1.0]hexane-3-carboxylate (100 mg, 0.25 mmol) obtained in step-2 of example 1 in dry DCM (5 mL). After the completion of the reaction as confirmed by TLC, the reaction mixture was purged with excess of nitrogen. The solvent was removed in vacuo to afford a gummy solid which was titurated with hexane to afford hydrochloric acid salt of 3-azabicyclo[3.1.0]hexan-6-yl(3,4-dichlorophenyl)methanone O-ethyl oxime (75 mg, 86%) as a white solid as a mixture of isomers.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[CH:4][C:5]([N:16]2[CH:20]=[N:19][N:18]=[C:17]2[CH2:21][N:22]2[C:26](=[O:27])[C:25]3=[CH:28][CH:29]=[CH:30][CH:31]=[C:24]3[C:23]2=[O:32])=[C:6]([CH:15]=1)[C:7]([C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1)=[O:8].C(=O)(O)[O-].[Na+]>>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([N:16]2[C:17]([CH2:21][N:22]3[C:26](=[O:27])[C:25]4=[CH:28][CH:29]=[CH:30][CH:31]=[C:24]4[C:23]3=[O:32])=[N:18][N:19]=[C:20]2[CH2:21][N:22]([CH2:26][CH2:25][CH3:28])[CH2:23][CH2:24][CH3:31])=[C:6]([CH:15]=1)[C:7]([C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1)=[O:8]
Reactant: O=C(c1ccccc1)c1cc(Cl)ccc1-n1cnnc1CN1C(=O)c2ccccc2C1=O
Agent: O=C([O-])O
Agent: [Na+]
Product: CCCN(CCC)Cc1nnc(CN2C(=O)c3ccccc3C2=O)n1-c1ccc(Cl)cc1C(=O)c1ccccc1

Procedure:
In the manner given in Example 13, 5-chloro-2-[3-(phthalimidomethyl)-4H-1,2,4-triazol-4-yl]benzophenone is reacted with the above suspension then neutralized with sodium bicarbonate to give 5-chloro-2-[3-[(dipropylamino)-methyl] -5-(phthalimidomethyl)-4H-1,2,4-triazol-4-yl]-benzophenone.
Reaction SMILES: [O:1]1[CH:5]=[CH:4][CH:3]=[C:2]1[C:6]1[N:10]([C:11]2[CH:16]=[CH:15][C:14]([O:17][CH3:18])=[CH:13][CH:12]=2)[N:9]=[C:8]([C:19]([NH2:21])=O)[CH:7]=1.N1C=CC=CC=1.O1CCOCC1.FC(F)(F)C(OC(=O)C(F)(F)F)=O>C(OCC)(=O)C.O>[O:1]1[CH:5]=[CH:4][CH:3]=[C:2]1[C:6]1[N:10]([C:11]2[CH:16]=[CH:15][C:14]([O:17][CH3:18])=[CH:13][CH:12]=2)[N:9]=[C:8]([C:19]#[N:21])[CH:7]=1
Reactant: COc1ccc(-n2nc(C(N)=O)cc2-c2ccco2)cc1
Solvent: CCOC(C)=O
Solvent: c1ccncc1
Solvent: C1COCCO1
Product: COc1ccc(-n2nc(C#N)cc2-c2ccco2)cc1
Reaction time: 0.67 h
Yield: 80 %

Procedure:
Part E. To 5-(2-furyl)-1-(4-methoxyphenyl)-1H-pyrazole-3-carboxamide (2.0 g, 6.6 mmol) was added pyridine (1.6 mL, 20 mmol) and dioxane (66 mL). Trifluoroacetic anhydride (1.9 mL, 13 mmol) was added dropwise over 2 min, and the resulting suspension was stirred for 40 min. The now clear red solution was poured into water (70 mL) and ethyl acetate (70 mL). The layers were separated, and the organic layer was washed with 1N aqueous hydrochloric acid (2×50 mL), saturated aqueous sodium chloride, and dried over sodium sulfate. The organic layers were concentrated, and the resulting residue was purified by radial chromatography (20-80% ethyl acetate in hexanes) to afford 5-(2-furyl)-1-(4-methoxyphenyl)-1H-pyrazole-3-carbonitrile (1.4 g, 74%) as an orange solid. LC/MS (ESI+): 266.0 (M+H)+. 1H NMR (CDCl3) δ 7.44 (br m, 1H), 7.34 (d, 2H), 7.01 (s, 1H), 7.00 (d, 2H), 6.34 (m, 1H), 5.92 (d, 1H), 3.85 (s, 3H).
Reaction SMILES: C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.[OH:20][C:21]1[CH:22]=[CH:23][CH:24]=[C:25]2[C:30]=1[N:29]=[C:28]([CH3:31])[CH:27]=[CH:26]2.C1C=CC(COC(/N=N/C(OCC2C=CC=CC=2)=O)=O)=CC=1.[NH2:54][C:55]1[CH:64]=[CH:63][C:62]2[C:57](=[C:58]([O:65][CH:66]([CH3:71])[CH2:67][CH2:68][CH2:69]O)[CH:59]=[CH:60][CH:61]=2)[N:56]=1>C1COCC1>[CH3:71][CH:66]([O:65][C:58]1[CH:59]=[CH:60][CH:61]=[C:62]2[C:57]=1[N:56]=[C:55]([NH2:54])[CH:64]=[CH:63]2)[CH2:67][CH2:68][CH2:69][O:20][C:21]1[CH:22]=[CH:23][CH:24]=[C:25]2[C:30]=1[N:29]=[C:28]([CH3:31])[CH:27]=[CH:26]2
Reactant: CC(CCCO)Oc1cccc2ccc(N)nc12
Reactant: Cc1ccc2cccc(O)c2n1
Agent: O=C(/N=N/C(=O)OCc1ccccc1)OCc1ccccc1
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: C1CCOC1
Product: Cc1ccc2cccc(OCCCC(C)Oc3cccc4ccc(N)nc34)c2n1
Reaction time: 0.08 h

Procedure:
A 20 mL scintillation vial with a septum cap was charged with PS-PPh3 resin (Aldrich Chemical Co., Inc, 90 mg, 4.4 equiv), 8-hydroxyquinaldine (1.5 equiv) and DBAD (22 mg, 1.6 equiv) and purged by passing a stream of N2 for 45 seconds. Anhydr. THF (3 mL) was added and the contents of the vial were shaken for 5 min. Then, a solution of 4-((2-aminoquinolin-8-yl)oxy)pentan-1-ol (15.0 mg/mL; 1.0 mL, 0.061 mmol)) in anhydr. THF (1 mL) was added and the resulting suspension was agitated at room temperature for 6 h. Following this, DBAD (22 mg, 1.6 equiv) was added and the mixture was agitated at room temperature for additional 12 h. The suspension was filtered, and the resin washed with THF (3×3.0 mL). The filtrate and washings were combined and evaporated in vacuo. The residue was then treated with 6.0 mL of 4 M HCl in dioxane at room temperature for 6 h. The resulting solution was evaporated in vacuo. The residue was dissolved in 1.5 mL of a 1:1 mixture of DMSO/MeOH and purified by preparative reverse-phase HPLC. 1H NMR (500 MHz, CDCl3) δ ppm 8.61 (d, 1H), 7.89 (d, 1H), 7.66 (m, 2H), 7.52 (d, 1H), 7.29 (m, 3H), 7.15 (m, 2H), 4.74 (m, 1H), 4.31 (m, 2H), 3.09 (s, 3H), 2.36 (m, 2H), 2.05 (m, 2H), 1.44 (d, 3H); MS (DCI/NH3) m/z 388 [M+H]+.
Reaction SMILES: [Br:1][C:2]1[C:3](Cl)=[C:4]2[C:10]([C:11]3[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=3[O:17][CH3:18])=[CH:9][N:8]([CH2:19][O:20][CH2:21][CH2:22][Si:23]([CH3:26])([CH3:25])[CH3:24])[C:5]2=[N:6][CH:7]=1.[CH3:28][NH:29][CH2:30][CH2:31][OH:32]>>[Br:1][C:2]1[C:3]([N:29]([CH3:28])[CH2:30][CH2:31][OH:32])=[C:4]2[C:10]([C:11]3[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=3[O:17][CH3:18])=[CH:9][N:8]([CH2:19][O:20][CH2:21][CH2:22][Si:23]([CH3:26])([CH3:25])[CH3:24])[C:5]2=[N:6][CH:7]=1
Reactant: COc1ccccc1-c1cn(COCC[Si](C)(C)C)c2ncc(Br)c(Cl)c12
Reactant: CNCCO
Product: COc1ccccc1-c1cn(COCC[Si](C)(C)C)c2ncc(Br)c(N(C)CCO)c12
Temperature: 145 °C
Yield: 65.7 %

Procedure:
5-Bromo-4-chloro-3-(2-methoxy-phenyl)-1-(2-trimethylsilanyl-ethoxymethyl)-1H-pyrrolo[2,3-b]pyridine (94 mg, 0.201 mmol) was combined 2-(methylamino)ethanol (161 μL, 2.01 mmol) in a sealed tube and heated for 15 hours at 145° C. The crude product was purified by flash silica gel chromatography using a gradient of ethyl acetate in hexanes to afford 2-{[5-Bromo-3-(2-methoxy-phenyl)-1-(2-trimethylsilanyl-ethoxymethyl)-1H-pyrrolo[2,3-b]pyridin-4-yl]-methyl-amino}-ethanol (67 mg, 0.132 mmol, 66% yield) as a clear oil.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:12]=[C:11]2[C:6]([CH2:7][CH2:8][CH2:9][CH:10]2[C:13]([OH:15])=O)=[CH:5][CH:4]=1.[Br:16][C:17]1[CH:22]=[CH:21][C:20]([CH2:23][NH:24][C:25]2[CH:30]=[CH:29][C:28]([CH:31]([CH3:33])[CH3:32])=[CH:27][CH:26]=2)=[CH:19][CH:18]=1>>[Br:16][C:17]1[CH:18]=[CH:19][C:20]([CH2:23][N:24]([C:25]2[CH:26]=[CH:27][C:28]([CH:31]([CH3:33])[CH3:32])=[CH:29][CH:30]=2)[C:13]([CH:10]2[C:11]3[C:6](=[CH:5][CH:4]=[C:3]([O:2][CH3:1])[CH:12]=3)[CH2:7][CH2:8][CH2:9]2)=[O:15])=[CH:21][CH:22]=1
Reactant: CC(C)c1ccc(NCc2ccc(Br)cc2)cc1
Reactant: COc1ccc2c(c1)C(C(=O)O)CCC2
Product: COc1ccc2c(c1)C(C(=O)N(Cc1ccc(Br)cc1)c1ccc(C(C)C)cc1)CCC2
Yield: 14.7 %

Procedure:
By the reaction and treatment in the same manner as in Example 1 using 7-methoxy-1,2,3,4-tetrahydronaphthalene-1-carboxylic acid (1.5 g) and [(4-bromophenyl)methyl](4-isopropylphenyl)amine (2.21 g) as starting materials, N-[(4-bromophenyl)methyl]-N-(4-isopropylphenyl)-7-methoxy-1,2,3,4-tetrahydronaphthalene-1-carboxamide (0.526 g) was obtained. melting point: 85° C.
Reaction SMILES: [CH:1]12[CH2:7][CH:4]([CH2:5][CH2:6]1)[CH2:3][C@@H:2]2[NH:8][C:9]1[C:14]([N+:15]([O-])=O)=[CH:13][N:12]=[C:11]2[CH:18]=[CH:19][S:20][C:10]=12>[Pd].CO>[CH:1]12[CH2:7][CH:4]([CH2:5][CH2:6]1)[CH2:3][C@@H:2]2[NH:8][C:9]1[C:14]([NH2:15])=[CH:13][N:12]=[C:11]2[CH:18]=[CH:19][S:20][C:10]=12
Reactant: O=[N+]([O-])c1cnc2ccsc2c1N[C@H]1CC2CCC1C2
Agent: [Pd]
Solvent: CO
Product: Nc1cnc2ccsc2c1N[C@H]1CC2CCC1C2

Procedure:
A mixture of N-[(2S)-bicyclo[2.2.1]hept-2-yl]-6-nitrothieno[3,2-b]pyridin-7-amine (0.080 g, 0.28 mmol) and 10% palladium on carbon (0.03 g) in methanol (3 mL) was subjected to balloon pressure of H2 at room temperature for 1 h. The mixture was filtered and the filtrate concentrated to give the desired product, which was used directly in the next step without further purification. LCMS calculated for C14H18N3S (M+H)+: m/z=260.1. Found: 260.0.
Reaction SMILES: [Cl:1][C:2]1[C:10]([Cl:11])=[C:9]2[C:5]([CH2:6][CH:7]([C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=3)[C:8]2=[O:12])=[CH:4][C:3]=1[O:19][CH2:20][C:21]([O:23][CH3:24])=[O:22].Br[CH2:26][C:27]#[C:28][Si:29]([CH3:32])([CH3:31])[CH3:30]>C1CCCCC1.C(Cl)Cl>[Cl:1][C:2]1[C:10]([Cl:11])=[C:9]2[C:5]([CH2:6][C:7]([C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=3)([CH2:26][C:27]#[C:28][Si:29]([CH3:32])([CH3:31])[CH3:30])[C:8]2=[O:12])=[CH:4][C:3]=1[O:19][CH2:20][C:21]([O:23][CH3:24])=[O:22]
Reactant: COC(=O)COc1cc2c(c(Cl)c1Cl)C(=O)C(c1ccccc1)C2
Reactant: C[Si](C)(C)C#CCBr
Solvent: C1CCCCC1
Solvent: ClCCl
Product: COC(=O)COc1cc2c(c(Cl)c1Cl)C(=O)C(CC#C[Si](C)(C)C)(c1ccccc1)C2
Yield: 74 %

Procedure:
Reaction of methyl (6,7-dichloro-1-oxo-2-phenyl-5-indanyloxy)acetate with 1-bromo-3-(trimethylsilyl)-2-propyne according to Example 1, STEP (b), affords the title compound, m.p. 125.5°-127° (from cyclohexane-methylene chloride) in 74% yield.
Reaction SMILES: [C:1]([O:10]C)(=O)[C:2]1[C:3](=[CH:5][CH:6]=[CH:7][CH:8]=1)[SH:4].[C:12]([C:14]1[CH:19]=[C:18]([C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)[CH:17]=[CH:16][N:15]=1)#[N:13].C(N(CC)CC)C>C1(C)C=CC=CC=1>[C:20]1([C:18]2[CH:17]=[CH:16][N:15]=[C:14]([C:12]3[S:4][C:3]4[CH:5]=[CH:6][CH:7]=[CH:8][C:2]=4[C:1](=[O:10])[N:13]=3)[CH:19]=2)[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=1
Reactant: N#Cc1cc(-c2ccccc2)ccn1
Reactant: COC(=O)c1ccccc1S
Solvent: CCN(CC)CC
Solvent: Cc1ccccc1
Product: O=c1nc(-c2cc(-c3ccccc3)ccn2)sc2ccccc12
Yield: 53 %

Procedure:
A mixture of methyl thiosalicylate (1.00 g, 5.9 mmol), 2-cyano-4-phenylpyridine (1.10 g, 5.9 mmol), triethylamine (1.30 ml, 9.0 mmol) and toluene (2.5 ml) was refluxed for 20 hrs. After cooling, the precipitated crystals were collected by filtration and recrystallized from ethanol to give the titled compound (0.99 g, 53%).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([N+:9]([O-:11])=[O:10])=[CH:5][C:4]=1[OH:12].[Si:13](Cl)([C:16]([CH3:19])([CH3:18])[CH3:17])([CH3:15])[CH3:14].C(N(C(C)C)C(C)C)C.O>CN(C=O)C>[C:16]([Si:13]([O:12][C:4]1[CH:5]=[C:6]([N+:9]([O-:11])=[O:10])[CH:7]=[CH:8][C:3]=1[O:2][CH3:1])([CH3:15])[CH3:14])([CH3:19])([CH3:18])[CH3:17]
Reactant: COc1ccc([N+](=O)[O-])cc1O
Reactant: CC(C)(C)[Si](C)(C)Cl
Solvent: CCN(C(C)C)C(C)C
Solvent: O
Solvent: CN(C)C=O
Product: COc1ccc([N+](=O)[O-])cc1O[Si](C)(C)C(C)(C)C
Temperature: 25 °C
Reaction time: 3 h
Yield: 63.4 %

Procedure:
A mixture of 2-methoxy-5-nitrophenol (3.0 g, 17.8 mmol), tert-butyldimethylsilyl chloride (3.2 g, 21.4 mmol), and ethyldiisopropylamine (5.8 g, 44.5 mmol) in DMF (50 mL) was stirred at room temperature for 3 hours. The mixture was poured into water (100 mL) and extracted with methylene chloride (3×100 mL). The combined organic extracts were washed with water (5×100 mL) and dried (MgSO4), and the solvent was evaporated under vacuum. The residue was recrystallized from ethanol-water, providing 3.2 g of the product as white crystals, in 64% yield: 1H NMR (CDCl3) δ 0.19 (s, 6H), 1.01 (s, 9H), 3.91 (s, 3H), 6.89 (d, J=8.9 Hz, 1H), 7.71 (d, J=2.8 Hz, 1H), 7.89 (dd, J=8.9 Hz, J=2.8 Hz, 1H).
Reaction SMILES: [C:1]([C:3]1[CH:8]=[CH:7][N:6]=[CH:5][CH:4]=1)#[N:2].[C:9]1([CH2:15]C(O)=O)[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1.FC(F)(F)C(O)=O.[OH-].[Na+]>[N+]([O-])([O-])=O.[Ag+].ClC1C=CC=CC=1.O>[CH2:15]([C:5]1[CH:4]=[C:3]([C:1]#[N:2])[CH:8]=[CH:7][N:6]=1)[C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1
Reactant: N#Cc1ccncc1
Reactant: O=C(O)Cc1ccccc1
Agent: [Ag+]
Agent: O=[N+]([O-])[O-]
Agent: [Na+]
Solvent: O
Solvent: Clc1ccccc1
Solvent: O=C(O)C(F)(F)F
Product: N#Cc1ccnc(Cc2ccccc2)c1
Temperature: 50 °C
Reaction time: 2 h
Yield: 60.1 %

Procedure:
p-cyanopyridine (4.00 g, 38.4 mmol) was added to a 1:1 mixture of chlorobenzene/water (750 mL) in a 1 L round-bottom flask. Phenylacetic acid (14.6 g, 107.5 mmol), (NH4)2S2O8 (17.1 g, 74.9 mmol), trifluoroacetic acid (4.38 g, 38.4 mmol) and AgNO3 (0.510 g, 3.0 mmol) were added and the heterogeneous mixture was vigorously stirred at 50° C. for 2 h. The reaction was cooled down to 0° C. and 8 M NaOH was added slowly until pH 9-10. The mixture was filtered through Celite and extracted with EtOAc (×3). The combined organic extracts were dried with MgSO4 and the solvent removed in vacuo. The dark-brown oil was purified via flash chromatography (1:5 EtOAc/Hexane) to give a brown oil (4.480 g, 61%); 1H NMR (400 MHz, CDCl3): δ 4.19 (s, 2H), 7.23-7.35 (m, 7H), 8.68 (d, J=5.2 Hz, 1H); 13C NMR (100 MHz, CDCl3): δ 44.4, 120.8, 122.7, 124.6, 126.9, 128.5, 128.9, 129.1, 137.9, 150.2, 162.7; HRMS-EI (m/z): [M+H+] calcd for [C13HN11N2]+, 195.0922. found, 195.0917.
Reaction SMILES: [O:1]=[C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[C:9]([CH2:12][N:13]([CH2:36][C:37]#[CH:38])[C:14]3[CH:35]=[CH:34][C:17]([C:18]([NH:20][C@H:21]([C:29]([O:31]CC)=[O:30])[CH2:22][CH2:23][C:24]([O:26]CC)=[O:25])=[O:19])=[CH:16][CH:15]=3)[CH:10]=2)[N:5]=[CH:4][N:3]1COC(=O)C(C)(C)C.O>CCO>[O:1]=[C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[C:9]([CH2:12][N:13]([CH2:36][C:37]#[CH:38])[C:14]3[CH:15]=[CH:16][C:17]([C:18]([NH:20][C@H:21]([C:29]([OH:31])=[O:30])[CH2:22][CH2:23][C:24]([OH:26])=[O:25])=[O:19])=[CH:34][CH:35]=3)[CH:10]=2)[N:5]=[CH:4][NH:3]1
Reactant: C#CCN(Cc1ccc2ncn(COC(=O)C(C)(C)C)c(=O)c2c1)c1ccc(C(=O)N[C@@H](CCC(=O)OCC)C(=O)OCC)cc1
Solvent: CCO
Solvent: O
Product: C#CCN(Cc1ccc2nc[nH]c(=O)c2c1)c1ccc(C(=O)N[C@@H](CCC(=O)O)C(=O)O)cc1
Reaction time: 0.67 h

Procedure:
A mixture of the gummy triester (5)(0.633 g, 0.001 mole), H2O (18 mL), EtOH (18 mL), and 1.00N NaOHaq (5 mL, 0.005 mole) was placed in a conical flask and stirred vigorously (magnetic stirrer) for 40 minutes to give a pale yellow solution. This solution was kept at 22° C. for 18.5 hours. It was then filtered through a bed of Celite (carbon treatment) and the clear filtrate acidified to pH 2.5 with 1.00 N HClaq. The resulting white gelatinous precipitate of the product was centrifuged (1500g/30 minutes) and washed by three cycles of resuspension (H2 0: 80 mL, 80 mL, and 40 mL)--centrifugation--decantation. The pellet was dried in vacuo over P2 05 --first at 22° C./24 hours in a desiccator and then at 80° C./4 hours in a pistol. A pale yellow amorphous solid was obtained (0.312 g, 67.5%),
Reaction SMILES: [OH-].[Li+].C[O:4][C:5](=[O:22])[C:6]1[CH:11]=[C:10]([O:12][S:13]([CH3:16])(=[O:15])=[O:14])[N:9]=[C:8]([NH:17][CH:18]([CH2:20][CH3:21])[CH3:19])[CH:7]=1.Cl>C1COCC1>[CH:18]([NH:17][C:8]1[CH:7]=[C:6]([CH:11]=[C:10]([O:12][S:13]([CH3:16])(=[O:15])=[O:14])[N:9]=1)[C:5]([OH:22])=[O:4])([CH2:20][CH3:21])[CH3:19]
Reactant: CCC(C)Nc1cc(C(=O)OC)cc(OS(C)(=O)=O)n1
Agent: Cl
Agent: [Li+]
Agent: [OH-]
Solvent: C1CCOC1
Product: CCC(C)Nc1cc(C(=O)O)cc(OS(C)(=O)=O)n1
Temperature: 25 °C
Reaction time: 12 h

Procedure:
Add 1 N lithium hydroxide (2 mL) to a solution of 2-sec-butylamino-6-methanesulfonyloxy-isonicotinic acid methyl ester (235 mg, 0.743 mmol) in THF (15 mL) at 0° C. Warm to room temperature and stir for 12 h. Acidify with 5% aqueous HCl to about pH=3, extract with ethyl acetate, dry (magnesium sulfate), and concentrate to give the title compound.
Reaction SMILES: [C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][C:11]([CH2:20][CH2:21][C:22](OC)=[O:23])([CH2:14][CH2:15][C:16]([O:18][CH3:19])=[O:17])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].CC([O-])(C)C.[K+]>C1COCC1>[O:23]=[C:22]1[CH2:21][CH2:20][C:11]2([CH2:10][CH2:9][N:8]([C:6]([O:5][C:1]([CH3:4])([CH3:2])[CH3:3])=[O:7])[CH2:13][CH2:12]2)[CH2:14][CH:15]1[C:16]([O:18][CH3:19])=[O:17]
Reactant: COC(=O)CCC1(CCC(=O)OC)CCN(C(=O)OC(C)(C)C)CC1
Agent: CC(C)(C)[O-]
Agent: [K+]
Solvent: C1CCOC1
Product: COC(=O)C1CC2(CCC1=O)CCN(C(=O)OC(C)(C)C)CC2
Temperature: 25 °C
Reaction time: 2 h
Yield: 78 %

Procedure:
Dimethyl 3,3′-(1-(tert-butoxycarbonyl)piperidine-4,4-diyl)dipropanoate (600 mg, 1.68 mmol) was dissolved in dry THF (10 ml) and a solution of t-BuOK (417 mg, 3.6 mmol) in THF was added at ice cold reaction conditions. The reaction mixture was stirred at room temperature for 2 h. TLC revealed completion of the reaction. The solvent was evaporated to dryness, the residue diluted with ethyl acetate and washed with water and brine. The organic layer was dried over Na2SO4, concentrated to dryness and purified by column chromatography to obtain the desired compound. Yield: 78%
Reaction SMILES: [CH3:1][S:2](Cl)(=[O:4])=[O:3].[CH2:6]1[CH:14]2[N:9]([CH2:10][CH2:11][CH:12]([C:15]3[C:23]4[C:18](=[CH:19][CH:20]=[C:21]([NH2:24])[CH:22]=4)[NH:17][CH:16]=3)[CH2:13]2)[CH2:8][CH2:7]1.C(N(CC)CC)C.[OH-].[NH4+]>CN(C)C=O.CO.C(Cl)Cl.O>[CH3:1][S:2]([N:17]1[C:18]2[C:23](=[CH:22][C:21]([NH2:24])=[CH:20][CH:19]=2)[C:15]([CH:12]2[CH2:13][CH:14]3[N:9]([CH2:8][CH2:7][CH2:6]3)[CH2:10][CH2:11]2)=[CH:16]1)(=[O:4])=[O:3]
Reactant: Nc1ccc2[nH]cc(C3CCN4CCCC4C3)c2c1
Reactant: CS(=O)(=O)Cl
Agent: [NH4+]
Agent: [OH-]
Solvent: CO
Solvent: CN(C)C=O
Solvent: ClCCl
Product: CS(=O)(=O)n1cc(C2CCN3CCCC3C2)c2cc(N)ccc21
Temperature: 25 °C
Reaction time: 2.5 h
Yield: 50.4 %

Procedure:
The methanesulfonyl chloride (215 mg, 1.87 mmol) was added dropwise to a solution of the 3-(octahydroindolizin-7-yl)-5-amino-1H-indole (320 mg, 1.25 mmol) and triethylamine (0.5 ml) in 10 ml of dimethylformamide. The reaction was stirred at room temperature for 2.5 hours. The reaction was diluted with methanol and concentrated to give a dark semi-solid. This material was dissolved in a mixture of methylene chloride and water, made basic with an ammonium hydroxide solution, then extracted with methylene chloride. The extract was dried over sodium sulfate and concentrated to give a reddish brown oil. The material was purified on a flash column using silica gel (20% methanol in methylene chloride (ammonium hydroxide) as eluent) to give 210 mg of product. (49.7%).
Reaction SMILES: [F:1][C:2]1[C:7]2[N:8]=[C:9]([CH3:11])[NH:10][C:6]=2[CH:5]=[C:4]([NH2:12])[CH:3]=1.C[Si]([N-][Si](C)(C)C)(C)C.[Li+].[C:23](=[N:36]N)([C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1)[C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1.Cl>CN1CCOCC1>[C:23](=[N:36][NH:12][C:4]1[CH:3]=[C:2]([F:1])[C:7]2[NH:8][C:9]([CH3:11])=[N:10][C:6]=2[CH:5]=1)([C:30]1[CH:31]=[CH:32][CH:33]=[CH:34][CH:35]=1)[C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1
Reactant: NN=C(c1ccccc1)c1ccccc1
Reactant: Cc1nc2c(F)cc(N)cc2[nH]1
Agent: C[Si](C)(C)[N-][Si](C)(C)C
Agent: Cl
Agent: [Li+]
Solvent: CN1CCOCC1
Product: Cc1nc2cc(NN=C(c3ccccc3)c3ccccc3)cc(F)c2[nH]1
Temperature: 100 °C
Reaction time: 2 h

Procedure:
In a separate reaction container, 7-fluoro-2-methyl-3H-benzimidazol-5-yl amine (100 mg, 0.44 mmol), lithium bis(trimethylsilyl) amide (190 mg, 1.1 mmol), and benzophenone hydrazone (94.3 mg, 0.48 mmol) were dissolved in N-methyl-morpholine (0.5 ml) under a nitrogen atmosphere. Then, the prepared solution containing the catalyst was added thereto. After deaeration, this was heated and stirred at 100° C. under a nitrogen atmosphere for two hours. The reaction mixture was cooled to room temperature, and then an aqueous solution of 6 M hydrochloric acid (0.5 ml) was added thereto. The organic layer was isolated, and concentrated under reduced pressure. Thus, crude N-benzhydrylidene-N′-(7-fluoro-2-methyl-1H-benzimidazol-5-yl)-hydrazine was obtained. The obtained crude product was used in subsequent reactions without being purified.