Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: CC(OI1(OC(C)=O)(OC(C)=O)OC(=O)C2C1=CC=CC=2)=O.[OH:23][CH2:24][CH2:25][C:26]1[CH:27]=[C:28]([N:32]2[CH2:36][CH2:35][O:34][C:33]2=[O:37])[CH:29]=[CH:30][CH:31]=1>ClCCl>[O:37]=[C:33]1[N:32]([C:28]2[CH:27]=[C:26]([CH2:25][CH:24]=[O:23])[CH:31]=[CH:30][CH:29]=2)[CH2:36][CH2:35][O:34]1
Reactant: O=C1OCCN1c1cccc(CCO)c1
Agent: CC(=O)OI1(OC(C)=O)(OC(C)=O)OC(=O)c2ccccc21
Solvent: ClCCl
Product: O=CCc1cccc(N2CCOC2=O)c1
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 89 %

Procedure:
1,1,1-Tris(acetyloxy)-1,1-dihydro-1,2-benziodoxol-3(1H)-one (Dess-Martin periodinane, 709 mg, 1.67 mmol) was added to a solution of 3-[3-(2-hydroxyethyl)phenyl]-1,3-oxazolidin-2-one (315 mg, 1.52 mmol) in dichloromethane (10 mL). The mixture was stirred at room temperature for 30 min, then washed with aqueous sodium hydroxide solution (1M, 10 mL). The separated organic layer the latter was dried over magnesium sulfate and concentrated under reduced pressure affording the title compound in 89% yield (278 mg). The compound was used without further purification in the next step.
Reaction SMILES: C(O[C:6]([N:8]1[CH2:13][CH:12]=[C:11]([C:14]2[CH:19]=[C:18]([N+:20]([O-])=O)[CH:17]=[CH:16][C:15]=2[F:23])[CH2:10][CH2:9]1)=O)(C)(C)C.C1COCC1.[H-].[Al+3].[Li+].[H-].[H-].[H-]>O>[F:23][C:15]1[CH:16]=[CH:17][C:18]([NH2:20])=[CH:19][C:14]=1[C:11]1[CH2:12][CH2:13][N:8]([CH3:6])[CH2:9][CH:10]=1
Reactant: CC(C)(C)OC(=O)N1CC=C(c2cc([N+](=O)[O-])ccc2F)CC1
Agent: [Al+3]
Agent: [H-]
Agent: [Li+]
Solvent: O
Solvent: C1CCOC1
Product: CN1CC=C(c2cc(N)ccc2F)CC1
Temperature: 25 °C
Reaction time: 16 h

Procedure:
A dried flask was charged with 4-(2-fluoro-5-nitrophenyl)-3,6-dihydro-2H-pyridine-1-carboxylic acid tert-butyl ester (645 mg, 2.00 mmol) and THF (10 mL). Lithium aluminium hydride (1M in THF, 20 mL, 20.0 mmol) was added slowly through a syringe under N2 (the reaction was very exothermic). The resulting mixture was stirred for 16 h at rt. Water was cautiously added to quench the reaction. The resulting mixture was filtered, and the filtrate was concentrated to dryness to give the title compound as a brown oil. 1H NMR (DMSO-d6, 400 MHz): δ=2.14 (s, 3H), 2.38-2.44 (m, 2H), 2.89-2.90 (m, 2H), 3.22 (brs, 2H), 5.95 (brs, 1H), 7.24-7.29 (m, 1H), 7.67-7.73 (m, 2H), 8.16 (s, 1H). MS (ES+): m/z 206.26 (100) [MH+]. HPLC: tR=1.68 min (ZQ2000, polar—5 min).
Reaction SMILES: [CH2:1]([C:5]1[CH:10]=[C:9]([C:11]2[O:15][N:14]=[C:13]([C:16]3[CH:21]=[CH:20][C:19]([CH2:22][C:23](O)=[O:24])=[CH:18][CH:17]=3)[N:12]=2)[CH:8]=[C:7]([CH3:26])[N:6]=1)[CH:2]([CH3:4])[CH3:3].[CH3:27][O:28][C:29]([CH:31]1[CH2:34][NH:33][CH2:32]1)=[O:30]>[OH-].[Na+].O1CCOCC1>[CH3:27][O:28][C:29]([CH:31]1[CH2:34][N:33]([C:23](=[O:24])[CH2:22][C:19]2[CH:20]=[CH:21][C:16]([C:13]3[N:12]=[C:11]([C:9]4[CH:8]=[C:7]([CH3:26])[N:6]=[C:5]([CH2:1][CH:2]([CH3:3])[CH3:4])[CH:10]=4)[O:15][N:14]=3)=[CH:17][CH:18]=2)[CH2:32]1)=[O:30].[CH2:1]([C:5]1[CH:10]=[C:9]([C:11]2[O:15][N:14]=[C:13]([C:16]3[CH:17]=[CH:18][C:19]([CH2:22][C:23]([N:33]4[CH2:34][CH:31]([C:29]([OH:28])=[O:30])[CH2:32]4)=[O:24])=[CH:20][CH:21]=3)[N:12]=2)[CH:8]=[C:7]([CH3:26])[N:6]=1)[CH:2]([CH3:4])[CH3:3]
Reactant: Cc1cc(-c2nc(-c3ccc(CC(=O)O)cc3)no2)cc(CC(C)C)n1
Reactant: COC(=O)C1CNC1
Agent: [Na+]
Agent: [OH-]
Solvent: C1COCCO1
Product: COC(=O)C1CN(C(=O)Cc2ccc(-c3noc(-c4cc(C)nc(CC(C)C)c4)n3)cc2)C1
Product: Cc1cc(-c2nc(-c3ccc(CC(=O)N4CC(C(=O)O)C4)cc3)no2)cc(CC(C)C)n1

Procedure:
1-(2-{4-[5-(2-Isobutyl-6-methyl-pyridin-4-yl)-[1,2,4]oxadiazol-3-yl]-phenyl}-acetyl)-azetidine-3-carboxylic acid methyl ester is prepared from {4-[5-(2-isobutyl-6-methyl-pyridin-4-yl)-[1,2,4]oxadiazol-3-yl]-phenyl}-acetic acid and azetidine-3-carboxylic acid methyl ester in analogy to Example 65; stirring this material in 3 N aq. NaOH/dioxane at rt for 20 h gives 1-(2-{4-[5-(2-isobutyl-6-methyl-pyridin-4-yl)-[1,2,4]oxadiazol-3-yl]-phenyl}-acetyl)-azetidine-3-carboxylic acid; LC-MS: tR=0.80, [M+1]+=435.02.
Reaction SMILES: [CH3:1][O:2][C:3]([C:5]1[CH:10]=[CH:9][C:8]([C:11]2[CH:12]=[CH:13][C:14]([CH2:21][CH2:22][C:23]([OH:25])=O)=[C:15]3[C:20]=2[N:19]=[CH:18][CH:17]=[CH:16]3)=[CH:7][CH:6]=1)=[O:4].C(Cl)(=O)C([Cl:29])=O.C1(C)C=CC=CC=1>ClCCl>[Cl:29][C:23](=[O:25])[CH2:22][CH2:21][C:14]1[CH:13]=[CH:12][C:11]([C:8]2[CH:9]=[CH:10][C:5]([C:3]([O:2][CH3:1])=[O:4])=[CH:6][CH:7]=2)=[C:20]2[C:15]=1[CH:16]=[CH:17][CH:18]=[N:19]2
Reactant: COC(=O)c1ccc(-c2ccc(CCC(=O)O)c3cccnc23)cc1
Reactant: O=C(Cl)C(=O)Cl
Solvent: Cc1ccccc1
Solvent: ClCCl
Product: COC(=O)c1ccc(-c2ccc(CCC(=O)Cl)c3cccnc23)cc1
Reaction time: 0.33 h

Procedure:
A solution of Example 201H (1.65 g, 4.92 mmol) in dichloromethane (15 mL) at room temperature was treated oxalyl chloride (344 mg, 2.71 mmol), stirred for 20 minutes, treated with toluene (25 mL), and concentrated to provide the desired product.
Reaction SMILES: C(OC(=O)[N:7]([CH2:18][CH2:19][C:20]1[C:28]2[C:23](=[CH:24][CH:25]=[C:26]([C:29](=[O:35])[N:30]([CH2:33][CH3:34])[CH2:31][CH3:32])[CH:27]=2)[NH:22][C:21]=1[C:36]1[CH:41]=[C:40]([Cl:42])[CH:39]=[C:38]([Cl:43])[CH:37]=1)[CH2:8][CH2:9][CH2:10][CH2:11][C:12]1[CH:13]=[N:14][CH:15]=[CH:16][CH:17]=1)(C)(C)C.C1(OC)C=CC=CC=1.FC(F)(F)C(O)=O>>[CH2:33]([N:30]([CH2:31][CH3:32])[C:29]([C:26]1[CH:27]=[C:28]2[C:23](=[CH:24][CH:25]=1)[NH:22][C:21]([C:36]1[CH:41]=[C:40]([Cl:42])[CH:39]=[C:38]([Cl:43])[CH:37]=1)=[C:20]2[CH2:19][CH2:18][NH:7][CH2:8][CH2:9][CH2:10][CH2:11][C:12]1[CH:13]=[N:14][CH:15]=[CH:16][CH:17]=1)=[O:35])[CH3:34]
Reactant: CCN(CC)C(=O)c1ccc2[nH]c(-c3cc(Cl)cc(Cl)c3)c(CCN(CCCCc3cccnc3)C(=O)OC(C)(C)C)c2c1
Solvent: COc1ccccc1
Solvent: O=C(O)C(F)(F)F
Product: CCN(CC)C(=O)c1ccc2[nH]c(-c3cc(Cl)cc(Cl)c3)c(CCNCCCCc3cccnc3)c2c1
Temperature: 0 °C
Reaction time: 1.5 h
Yield: 71.6 %

Procedure:
To a solution of {2-[2-(3,5-dichlorophenyl)-5-diethylcarbamoyl-1H-indol-3-yl]ethyl}-(4-pyridin-3-yl-butyl)carbamic acid tert-butyl ester (63 mg in 3 mL methylene chloride) at 0° C. was added 0.15 mL anisole followed by 0.76 miL trifluoroacetic acid and the mixture stirred at 0° C. After 1.5 hours, an additional charge of 0.5 mL trifluoroacetic acid was added and stirring continued for another hour at which time the mixture was concentrated in vacuo and the residual acid removed by azeotrope with toluene. Purification of the concentrate by flash chromatography on silica gel (methylene chloride:methanol:ammonium hydroxide, 90:6.5:1) gave the title compound (38 mg). m/e=537 (M)
Reaction SMILES: [Br:1][C:2]1[C:11]2[C:10]([CH3:13])([CH3:12])[CH2:9][CH:8]=[C:7]([CH:14]([CH3:16])[CH3:15])[C:6]=2[CH:5]=[C:4](/[C:17](/[CH3:30])=[C:18](/[F:29])\[CH:19]=[CH:20]\[C:21](\[CH3:28])=[CH:22]\[C:23]([O:25]CC)=[O:24])[C:3]=1[O:31][CH3:32].[OH-].[Na+].[CH2:35](O)C>>[Br:1][C:2]1[C:11]2[C:10]([CH3:13])([CH3:12])[CH2:9][CH:8]=[C:7]([CH:14]([CH3:16])[CH3:15])[C:6]=2[CH:5]=[C:4](/[C:17](/[CH2:30][CH3:35])=[C:18](/[F:29])\[CH:19]=[CH:20]\[C:21](\[CH3:28])=[CH:22]\[C:23]([OH:25])=[O:24])[C:3]=1[O:31][CH3:32]
Reactant: CCOC(=O)/C=C(C)/C=C/C(F)=C(/C)c1cc2c(c(Br)c1OC)C(C)(C)CC=C2C(C)C
Reactant: CCO
Agent: [Na+]
Agent: [OH-]
Product: CC/C(=C(F)/C=C/C(C)=C/C(=O)O)c1cc2c(c(Br)c1OC)C(C)(C)CC=C2C(C)C

Procedure:
As described in General Procedure J-1, ethyl (2E,4E,6E)-7-(4-bromo-8-isopropyl-3-methoxy-5,5-dimethyl-5,6-dihydro-naphthalen-2-yl)-6-fluoro-3-methyl-octa-2,4,6-trienoate (Compound A-157, 43 mg, 0.085 mmol) in ethanol was treated with a solution of 1 N NaOH to produce the title compound after purification by recrystallization from acetonitrile.
Reaction SMILES: [CH:1]1([NH2:7])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[N:8]1[C:17]2[C:12](=[CH:13][CH:14]=[CH:15][C:16]=2[S:18]([NH:21][C:22]2[CH:30]=[CH:29][CH:28]=[CH:27][C:23]=2[C:24](Cl)=[O:25])(=[O:20])=[O:19])[CH:11]=[CH:10][CH:9]=1>>[CH:1]1([NH:7][C:24](=[O:25])[C:23]2[CH:27]=[CH:28][CH:29]=[CH:30][C:22]=2[NH:21][S:18]([C:16]2[CH:15]=[CH:14][CH:13]=[C:12]3[C:17]=2[N:8]=[CH:9][CH:10]=[CH:11]3)(=[O:20])=[O:19])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1
Reactant: NC1CCCCC1
Reactant: O=C(Cl)c1ccccc1NS(=O)(=O)c1cccc2cccnc12
Product: O=C(NC1CCCCC1)c1ccccc1NS(=O)(=O)c1cccc2cccnc12
Yield: 57.4 %

Procedure:
50 mg of cyclohexylamine were reacted with 87 mg of 2-(quinoline-8-sulfonylamino)-benzoyl chloride in analogy to example 1 which resulted in 59 mg of an amorphous white solid. MS (ES): 410 (M+H)+
Reaction SMILES: [CH3:1][C:2]([O:17][Si:18]([CH3:21])([CH3:20])[CH3:19])([CH2:15][CH3:16])[C:3]#[C:4][Si:5]([CH3:14])([CH3:13])[CH2:6][CH2:7][SiH2:8][CH:9]=C(C)C.[Cl:22][C:23]1[CH:30]=[CH:29][C:26]([CH:27]=[CH2:28])=[CH:25][CH:24]=1.[C:31]1(C)C=CC=CC=1>>[CH3:1][C:2]([O:17][Si:18]([CH3:19])([CH3:20])[CH3:21])([CH2:15][CH3:16])[C:3]#[C:4][Si:5]([CH3:13])([CH3:14])[CH2:6][CH2:7][Si:8](/[CH:28]=[CH:27]/[C:26]1[CH:29]=[CH:30][C:23]([Cl:22])=[CH:24][CH:25]=1)([CH3:9])[CH3:31]
Reactant: Cc1ccccc1
Reactant: C=Cc1ccc(Cl)cc1
Reactant: CCC(C)(C#C[Si](C)(C)CC[SiH2]C=C(C)C)O[Si](C)(C)C
Product: CCC(C)(C#C[Si](C)(C)CC[Si](C)(C)/C=C/c1ccc(Cl)cc1)O[Si](C)(C)C

Procedure:
As in reaction conditions of Example XIX Step 2, to 1.81 mL of toluene, the 0.01 g carbonylchlorohydridebis(tricyclohexylphosphine)ruthenium(H) was added, and the reaction was carried out between the 1-{[3-methyl-3-(trimethylsiloxy)-1-pentynyl]dimethylsilyl}-2-(dimethylvinylsilyl)ethane obtained in Step 1 and 0.57 g 4-chlorostyrene. Product was separated under the purification conditions of Example XII. The product, 1-{[3-methyl-3-(trimethylsiloxy)-1-pentynyl]dimethylsilyl}-2-{[(E)-4-chlorostyryl]dimethylsilyl)ethane, was obtained with a total yield of 82% pure product in the form of an oily, yellow liquid.
Reaction SMILES: [CH3:1][C:2]1[CH:23]=[CH:22][C:5]2[N:6]([CH2:9][C:10]3[CH:21]=[CH:20][C:13]4[N:14]=[C:15](S(C)=O)[S:16][C:12]=4[CH:11]=3)[CH:7]=[N:8][C:4]=2[CH:3]=1.[NH2:24][C@@H:25]1[CH2:30][CH2:29][CH2:28][CH2:27][C@H:26]1[OH:31].CCN(C(C)C)C(C)C.CN1C(=O)CCC1>CCOC(C)=O>[CH3:1][C:2]1[CH:23]=[CH:22][C:5]2[N:6]([CH2:9][C:10]3[CH:21]=[CH:20][C:13]4[N:14]=[C:15]([NH:24][C@@H:25]5[CH2:30][CH2:29][CH2:28][CH2:27][C@H:26]5[OH:31])[S:16][C:12]=4[CH:11]=3)[CH:7]=[N:8][C:4]=2[CH:3]=1
Reactant: Cc1ccc2c(c1)ncn2Cc1ccc2nc(S(C)=O)sc2c1
Reactant: N[C@@H]1CCCC[C@H]1O
Solvent: CCOC(C)=O
Solvent: CCN(C(C)C)C(C)C
Solvent: CN1CCCC1=O
Product: Cc1ccc2c(c1)ncn2Cc1ccc2nc(N[C@@H]3CCCC[C@H]3O)sc2c1
Temperature: 130 °C
Yield: 26.5 %

Procedure:
A stirred mixture of 6-((5-methyl-1H-benzo[d]imidazol-1-yl)methyl)-2-(methylsulfinyl)benzo[d]thiazole (0.26 g, 0.76 mmol) from the previous step, (1R,2R)-2-aminocyclohexanol (0.26 g, 2.2 mmol), DIEA (0.98 g, 7.6 mmol) and NMP (2 mL) was heated at 130° C. for 12 h. The reaction mixture was cooled to rt, diluted with EtOAc (30 mL), and washed with water (10 mL×2). The organic layer was dried over Na2SO4, filtered, and concentrated under reduced pressure. The residue was purified by silica gel flash chromatography eluting with 3% MeOH in DCM to afford (1R,2R)-2-((6-((5-methyl-1H-benzo[d]imidazol-1-yl)methyl)benzo[d]thiazol-2-yl)amino)cyclohexanol (79 mg, 89%) as a white solid. 1H NMR (300 MHz, DMSO-d6) δ 8.30 (s, 1H), 7.91 (d, J=7.5 Hz, 1H), 7.61 (d, J=2.0 Hz, 1H), 7.39-7.42 (m, 2H), 7.28 (d, J=8.1 Hz, 1H), 7.16 (dd, J=8.4, 1.8 Hz, 1H), 7.02 (d, J=7.2 Hz, 1H), 5.42 (s, 2H), 4.69 (d, J=5.1 Hz, 1H), 3.39 (m, 1H), 3.33 (m, 1H), 2.38 (s, 3H), 2.03 (m, 1H), 1.86 (m, 1H), 1.59-1.63 (m, 2H), 1.21-1.23 (m, 4H); LCMS (ESI) m/z 393 (M+H)+.
Reaction SMILES: CS[C:3]1[N:8]=[C:7]([C:9]2[CH:14]=[CH:13][C:12]([Cl:15])=[CH:11][C:10]=2[Cl:16])[C:6]([C:17]2[CH:22]=[CH:21][C:20]([Cl:23])=[CH:19][CH:18]=2)=[CH:5][N:4]=1.[CH3:24][C:25]([OH:34])([CH3:33])[C:26]1[CH:31]=[CH:30][C:29]([F:32])=[CH:28][CH:27]=1>>[CH3:24][C:25]([CH3:33])([O:34][C:3]1[N:8]=[C:7]([C:9]2[CH:14]=[CH:13][C:12]([Cl:15])=[CH:11][C:10]=2[Cl:16])[C:6]([C:17]2[CH:22]=[CH:21][C:20]([Cl:23])=[CH:19][CH:18]=2)=[CH:5][N:4]=1)[C:26]1[CH:31]=[CH:30][C:29]([F:32])=[CH:28][CH:27]=1
Reactant: CC(C)(O)c1ccc(F)cc1
Reactant: CSc1ncc(-c2ccc(Cl)cc2)c(-c2ccc(Cl)cc2Cl)n1
Product: CC(C)(Oc1ncc(-c2ccc(Cl)cc2)c(-c2ccc(Cl)cc2Cl)n1)c1ccc(F)cc1

Procedure:
2-Methylthio-5-(4-chlorophenyl)-4-(2,4-dichlorophenyl)pyrimidine from Reference Example 3 was reacted with α,α-dimethyl-4-fluorobenzyl alcohol according to the procedure described in Example 59 to afford 2-(α,α-dimethyl-4-fluorobenzyloxy)-4-(2,4-dichlorophenyl)-5-(4-chlorophenyl)pyrimidine (HRf): 1H-NMR 500 MHz (CDCl3): δ 1.91 (s, 6H), 6.90-7.00 (m, 5H), 7.20-7.25 (m, 3H), 7.30 (s, 1H), 7.41-7.45 (m, 2H), 8.40 (s, 1H).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:12]=[CH:11][C:10]([C:13](=[O:15])[CH3:14])=[CH:9][C:4]=1[C:5]([O:7]C)=[O:6].Cl>C(O)(=O)C>[CH3:1][O:2][C:3]1[CH:12]=[CH:11][C:10]([C:13](=[O:15])[CH3:14])=[CH:9][C:4]=1[C:5]([OH:7])=[O:6]
Reactant: COC(=O)c1cc(C(C)=O)ccc1OC
Agent: Cl
Solvent: CC(=O)O
Product: COc1ccc(C(C)=O)cc1C(=O)O

Procedure:
Methyl 2-methoxy-5-acetylbenzoate (Step A, 3 g, 14.4 mmol) was dissolved in acetic acid (80 ml) and then treated with c HCl (28 ml). The reaction mixture was refluxed for 4 hours, concentrated under reduced pressure and lyophilized to provide the title compound as cream color solid, which was used without further purification.
Reaction SMILES: Br[C:2]1[C:3]([C:31]#[N:32])=[CH:4][CH:5]=[C:6]2[C:14]=1[NH:13][C:12]1[C:11]([CH3:16])([CH3:15])[C:10]3[CH:17]=[C:18]([O:21][CH2:22][C@H:23]4[CH2:27][O:26][C:25]([CH3:29])([CH3:28])[O:24]4)[CH:19]=[CH:20][C:9]=3[C:8](=[O:30])[C:7]2=1.[Cu][C:34]#[N:35].O>CC(N(C)C)=O>[CH3:29][C:25]1([CH3:28])[O:24][C@@H:23]([CH2:22][O:21][C:18]2[CH:19]=[CH:20][C:9]3[C:8](=[O:30])[C:7]4[C:6]5[C:14](=[C:2]([C:34]#[N:35])[C:3]([C:31]#[N:32])=[CH:4][CH:5]=5)[NH:13][C:12]=4[C:11]([CH3:15])([CH3:16])[C:10]=3[CH:17]=2)[CH2:27][O:26]1
Reactant: CC1(C)OC[C@H](COc2ccc3c(c2)C(C)(C)c2[nH]c4c(Br)c(C#N)ccc4c2C3=O)O1
Reactant: N#C[Cu]
Solvent: O
Solvent: CC(=O)N(C)C
Product: CC1(C)OC[C@H](COc2ccc3c(c2)C(C)(C)c2[nH]c4c(C#N)c(C#N)ccc4c2C3=O)O1
Temperature: 200 °C
Reaction time: 1 h

Procedure:
Under nitrogen atmosphere, 4-bromo-8-((S)-2,2-dimethyl-[1,3]dioxolan-4-yl methoxy)-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile (Compound U6, 20.0 mg, 40.37 μmol) was dissolved in DMA (0.35 mL), added with copper (I) cyanide (18.1 mg, 201.9 μmol), and stirred at 200° C. for 1 hr under irradiation with microwave. The reaction solution was poured into water, extracted with ethyl acetate, washed with water and saturated brine, dried over sodium sulfate, and then filtered. The residues obtained after concentration under reduced pressure were purified by silica gel column chromatography (ethyl acetate/hexane) to obtain the title compound as a crude product.
Reaction SMILES: C(O[C:4](=[O:19])[C:5]([NH:7][C:8]1[CH:13]=[CH:12][C:11]([O:14][CH3:15])=[CH:10][C:9]=1[N+:16]([O-:18])=[O:17])=[O:6])C.C1(C)C=CC=CC=1.[CH2:27]([NH2:31])[CH2:28][CH2:29][CH3:30]>>[CH2:27]([NH:31][C:4](=[O:19])[C:5]([NH:7][C:8]1[CH:13]=[CH:12][C:11]([O:14][CH3:15])=[CH:10][C:9]=1[N+:16]([O-:18])=[O:17])=[O:6])[CH2:28][CH2:29][CH3:30]
Reactant: CCCCN
Reactant: CCOC(=O)C(=O)Nc1ccc(OC)cc1[N+](=O)[O-]
Solvent: Cc1ccccc1
Product: CCCCNC(=O)C(=O)Nc1ccc(OC)cc1[N+](=O)[O-]
Temperature: 25 °C
Reaction time: 10 h
Yield: 93.3 %

Procedure:
To a suspension of 44.0 g (164 mmol) of N-(4-methoxy-2-nitro-phenyl)oxalamic acid ethyl ester [J. Med. Chem., 18, 926 (1975)] and 330 ml toluene 16.8 ml (170 mmol) of n-butylamin is added under 20° C. The reaction mixture is stirred at room temperature for 10 h, then concentrated and the residue is crystallized with diethyl ether, the precipitated product is filtered off, washed with diethyl ether and dried to yield 45.3 g (93.3%) of the title compound. Mp.: 127-128° C. (diethyl ether).
Reaction SMILES: [O:1]1[CH:5]=[CH:4][CH:3]=[C:2]1[C:6]1[O:10][N:9]=[C:8]([C:11]([OH:13])=O)[CH:7]=1.[N:14]1([CH2:19][CH2:20][CH2:21][NH2:22])[CH:18]=[CH:17][N:16]=[CH:15]1.C1C=CC2N(O)N=NC=2C=1.C(Cl)CCl>CN(C=O)C>[N:14]1([CH2:19][CH2:20][CH2:21][NH:22][C:11]([C:8]2[CH:7]=[C:6]([C:2]3[O:1][CH:5]=[CH:4][CH:3]=3)[O:10][N:9]=2)=[O:13])[CH:18]=[CH:17][N:16]=[CH:15]1
Reactant: O=C(O)c1cc(-c2ccco2)on1
Reactant: NCCCn1ccnc1
Agent: On1nnc2ccccc21
Solvent: ClCCCl
Solvent: CN(C)C=O
Product: O=C(NCCCn1ccnc1)c1cc(-c2ccco2)on1
Temperature: 25 °C
Reaction time: 18 h
Yield: 35 %

Procedure:
To a solution of 5-furan-2-yl-isoxazole-3-carboxylic acid (7 mg) and 3-imidazol-1-yl-propyl amine (0.005 mL) in DMF was added 8 mg of HOBt, 9 mg of EDC and 0.014 mL of TEA. After stirring at room temperature for 18 hrs, the reaction solution was concentrated in vacuo. The obtained concentrate was purified by preparative HPLC to afford 4 mg of 5-furan-2-yl-isoxazole-3-carboxylic acid (3-imidazol-1-yl-propyl)-amide (Yield: 35%).
Reaction SMILES: [CH3:1][S:2][C:3]1[CH:4]=[C:5]([CH:7]=[CH:8][CH:9]=1)[NH2:6].C([O:12][CH:13]=[C:14]([C:20](OCC)=O)[C:15]([O:17][CH2:18][CH3:19])=[O:16])C>C1(OC2C=CC=CC=2)C=CC=CC=1>[OH:12][C:13]1[C:7]2[C:5](=[CH:4][C:3]([S:2][CH3:1])=[CH:9][CH:8]=2)[N:6]=[CH:20][C:14]=1[C:15]([O:17][CH2:18][CH3:19])=[O:16]
Reactant: CSc1cccc(N)c1
Reactant: CCOC=C(C(=O)OCC)C(=O)OCC
Solvent: c1ccc(Oc2ccccc2)cc1
Product: CCOC(=O)c1cnc2cc(SC)ccc2c1O
Temperature: 135 °C
Reaction time: 1.5 h

Procedure:
A neat mixture of 2.8 g of compound of 3-methylthioaniline and 4.0 g of diethyl ethoxymethylenemalonate is heated at 135° C. under a slow argon sweep for 1 h, then diluted with 25 mL of diphenyl ether and heated to 260° C., with maintenance of the argon sweep, and kept at that temperature for 90 min. The mixture is then cooled to ca 100° C. and added to 300 mL of stirred 1:1 ether-hexane. The precipitate is filtered, washed with hexane, and dried in vacuo to provide 1.35 g of crude material as a tan solid, which is recrystallized from acetic acid-water to afford 1.06 g of ethyl 4-hydroxy-7-(methylsulfanyl)-3-quinolinecarboxylate.
Reaction SMILES: C[Si](C)(C)[O-].[K+].C([O:9][C:10](=[O:25])[C:11]([S:14]([CH:17]1[CH2:22][CH2:21][CH:20]([O:23][CH3:24])[CH2:19][CH2:18]1)(=[O:16])=[O:15])([CH3:13])[CH3:12])C>C1COCC1>[CH3:24][O:23][CH:20]1[CH2:21][CH2:22][CH:17]([S:14]([C:11]([CH3:13])([CH3:12])[C:10]([OH:25])=[O:9])(=[O:16])=[O:15])[CH2:18][CH2:19]1
Reactant: CCOC(=O)C(C)(C)S(=O)(=O)C1CCC(OC)CC1
Agent: C[Si](C)(C)[O-]
Agent: [K+]
Solvent: C1CCOC1
Product: COC1CCC(S(=O)(=O)C(C)(C)C(=O)O)CC1
Temperature: 25 °C
Reaction time: 4 h
Yield: 80 %

Procedure:
Potassium trimethylsilanolate (3.1 g, 24.65 mmol) is added to a solution of 2-(4-methoxy-cyclohexanesulfonyl)-2-methyl-propionic acid ethyl ester (3.6 g, 12.3 mmol) in 100 mL of THF. After stirring the reaction mixture at room temperature for 4 h, the solvent is removed under reduced pressure, saturated aqueous NaHCO3 solution is added and the mixtures is extracted with ethyl acetate. The two phases are separated and the aqueous layer is acidified with 2N aqueous HCl solution and extracted with ethyl acetate; the combined organic extracts are washed with brine, dried (Na2SO4), filtered and concentrated under reduced pressure to afford 2.6 g of 2-(4-methoxy-cyclohexanesulfonyl)-2-methyl-propionic acid. Yield: 73%, over two steps. 1H-NMR (500 MHz, CHLOROFORM-d) δ ppm 1.21-1.37 (2H, m), 1.64-1.81 (8H, m), 2.19-2.32 (4H, m), 3.18-3.28 (1H, m), 3.40 (3H, s), 3.45 (1H, tt, J=11.96, 3.53 Hz); ES-MS: m/z 263 [M−H]
Reaction SMILES: C(O[NH:6][CH:7]1[CH:12]=[CH:11][C:10]([C:13](=[O:29])[CH2:14][C:15]2([OH:28])[CH2:20][CH2:19][N:18]([CH2:21][C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=3)[CH2:17][CH2:16]2)=[CH:9][C:8]1=C=O)(C)(C)C.[F:32][C:33]([F:38])([F:37])[C:34]([OH:36])=[O:35]>C(Cl)(Cl)Cl>[CH2:21]([N:18]1[CH2:17][CH2:16][C:15]([CH2:14][C:13]([C:10]2[CH:9]=[CH:8][C:7]([NH2:6])=[CH:12][CH:11]=2)=[O:29])([OH:28])[CH2:20][CH2:19]1)[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1.[F:32][C:33]([F:38])([F:37])[C:34]([O-:36])=[O:35]
Reactant: O=C(O)C(F)(F)F
Reactant: CC(C)(C)ONC1C=CC(C(=O)CC2(O)CCN(Cc3ccccc3)CC2)=CC1=C=O
Solvent: ClC(Cl)Cl
Product: Nc1ccc(C(=O)CC2(O)CCN(Cc3ccccc3)CC2)cc1
Product: O=C([O-])C(F)(F)F
Temperature: 25 °C

Procedure:
30 ml of chloroform was added to 2.07 g of N-t-butoxy-carbonyl-4-[(1-benzyl-4-hydroxypiperidin-4-yl)acetyl]aniline, trifluoroacetic acid was added thereto three times in a total amount of 8 ml, and the mixture was stirred at room temperature. Thereafter, the solvent was removed by distillation under reduced pressure, and the obtained residue was applied to silica gel column chromatography to obtain 1.14 g of the title compound as reddish white powder.
Reaction SMILES: [N:1]1[CH:6]=[CH:5][CH:4]=[C:3]([C:7]2[CH:8]=[C:9]([C:13]3[N:17]4[CH:18]=[CH:19][C:20]([CH:22]=[O:23])=[CH:21][C:16]4=[N:15][CH:14]=3)[CH:10]=[CH:11][CH:12]=2)[CH:2]=1.[CH3:24][Mg]Br.CO>O1CCCC1>[NH3:1].[N:1]1[CH:6]=[CH:5][CH:4]=[C:3]([C:7]2[CH:8]=[C:9]([C:13]3[N:17]4[CH:18]=[CH:19][C:20]([CH:22]([OH:23])[CH3:24])=[CH:21][C:16]4=[N:15][CH:14]=3)[CH:10]=[CH:11][CH:12]=2)[CH:2]=1
Reactant: C[Mg]Br
Reactant: O=Cc1ccn2c(-c3cccc(-c4cccnc4)c3)cnc2c1
Solvent: CO
Solvent: C1CCOC1
Product: CC(O)c1ccn2c(-c3cccc(-c4cccnc4)c3)cnc2c1
Product: N
Temperature: 25 °C
Reaction time: 16 h
Yield: 57 %

Procedure:
3-[3-(Pyridin-3-yl)phenyl]imidazo[1,2-α]pyridine-7-carboxaldehyde (100 mg, 0.33 mmol) in tetrahydrofuran (10 ml) was cooled to −78° C. before adding methylmagnesium bromide (1.3 ml of 0.3M solution in diethyl ether) dropwise over 10 min. Once addition was complete the reaction was allowed to warm to ambient temperature and stirring continued for 16 h. Methanol (1 ml) was added and the mixture partitioned between ethyl acetate and 10% ammonium chloride solution. The organic layer was washed with brine, dried over sodium sulphate and concentrated to give a yellow oil. This oil was purified by preparative thin layer chromatography eluting with dichloromethane/methanol/conc. ammonia (95:5:0.5) to afford the title compound (59 mg, 57%) as a white foam. 1H NMR (360 MHz, CDCl3) δH 1.55 (3H, d, J 6), 4.97 (1H, q, J 6), 6.91 (1H, dd, J 2 and 7) 7.37-7.43 (1H, m), 7.56-7.67 (4H, m), 7.65-7.74 (2H, m), 7.89-7.94 (1H, m), 8.33 (1H, d, J 7), 8.60-8.65 (1H, m), 8.89 (1H, s); m/z (ES+) 316 (M++H).
Reaction SMILES: CC(C)[C@H:3]([N:8]1[CH2:16][C:15]2[C:10](=[CH:11][C:12]([C:17]3[CH:22]=[CH:21][C:20]([N+:23]([O-:25])=[O:24])=[CH:19][CH:18]=3)=[CH:13][CH:14]=2)[C:9]1=[O:26])[C:4]([O:6][CH3:7])=[O:5].Br[CH2:29][C:30]1C=CC(C2C=CC([N+]([O-])=O)=CC=2)=C[C:31]=1C(OC)=O.Cl.NC1(C(OC)=O)CCC1>>[N+:23]([C:20]1[CH:19]=[CH:18][C:17]([C:12]2[CH:11]=[C:10]3[C:15]([CH2:16][N:8]([C:3]4([C:4]([O:6][CH3:7])=[O:5])[CH2:31][CH2:30][CH2:29]4)[C:9]3=[O:26])=[CH:14][CH:13]=2)=[CH:22][CH:21]=1)([O-:25])=[O:24]
Reactant: COC(=O)[C@H](C(C)C)N1Cc2ccc(-c3ccc([N+](=O)[O-])cc3)cc2C1=O
Reactant: COC(=O)c1cc(-c2ccc([N+](=O)[O-])cc2)ccc1CBr
Agent: COC(=O)C1(N)CCC1
Agent: Cl
Product: COC(=O)C1(N2Cc3ccc(-c4ccc([N+](=O)[O-])cc4)cc3C2=O)CCC1
Yield: 71 %

Procedure:
The compound of example 573 was prepared analogous to compound of example 5 by reaction of compound of example 4 with methyl 1-aminocyclobutanecarboxylate hydrochloride.
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[C:9]2[C:10]3[CH2:21][CH2:20][NH:19][CH2:18][CH2:17][C:11]=3[NH:12][C:13]=2[CH:14]=[CH:15][CH:16]=1.CC(C)=O.C(Cl)(Cl)Cl.[NH4+].[OH-]>C1COCC1>[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[C:9]2[C@@H:10]3[CH2:21][CH2:20][NH:19][CH2:18][CH2:17][C@H:11]3[NH:12][C:13]=2[CH:14]=[CH:15][CH:16]=1
Reactant: Fc1ccccc1-c1cccc2[nH]c3c(c12)CCNCC3
Agent: [NH4+]
Agent: [OH-]
Solvent: C1CCOC1
Solvent: CC(C)=O
Solvent: ClC(Cl)Cl
Product: Fc1ccccc1-c1cccc2c1[C@@H]1CCNCC[C@H]1N2
Temperature: 25 °C
Reaction time: 1.25 h

Procedure:
A solution of 10-(2-fluorophenyl)-1,2,3,4,5,6-hexahydroazepino[4,5-b]indole (0.49 g, 1.74 mmol) in THF (6 mL) was added dropwise to 1.5 M borane-THF complex (6 mL, 9 mmol) and stirred at room temperature for 1.25 hours. The excess borane was quenched with H2O and the mixture was added to TFA at 0° C. After 0.3 hours the reaction was diluted with H2O and concentrated in vacuo. The residue was diluted with H2O, made basic with 15% NaOH and extracted three times with CH2Cl2. The extracts were dried over MgSO4 and concentrated in vacuo to give a white solid which was passed through a column of silica gel with 1:19 acetone/CHCl3 with 1% NH4OH to give 0.25 g (51%) of a light brown solid as the title compound: 1H NMR (400 MHz, CDCl3) δ 7.38-7.33 (m, 2H), 7.21-7.10 (m, 3H), 6.69 (d, J=7.7Hz, 2H), 3.89 (dt, J=11.0 Hz, 3.5Hz, 1H), 3.60-3.53 (m, 1H), 3.18-3.12 (m, 1H), 2.94-2.88 (m, 1H), 2.83 (m, 1H), 2.74-2.72 (m, 1H), 2.21-2.16 (m, 1H), 1.97-1.87 (m, 1H), 1.67 (m, 1H), 1.26 (m, 1H); MS m/z 283.2 (M++H).