Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: Cl.Cl.[CH2:3]([O:5][C:6](=[O:12])[CH2:7][NH:8][CH2:9][CH2:10][NH2:11])[CH3:4].[C:13]1([C:19]2[S:23][C:22]([S:24](Cl)(=[O:26])=[O:25])=[N:21][N:20]=2)[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1>>[CH2:3]([O:5][C:6](=[O:12])[CH2:7][NH:8][CH2:9][CH2:10][NH:11][S:24]([C:22]1[S:23][C:19]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)=[N:20][N:21]=1)(=[O:25])=[O:26])[CH3:4]
Reactant: CCOC(=O)CNCCN
Reactant: O=S(=O)(Cl)c1nnc(-c2ccccc2)s1
Agent: Cl
Product: CCOC(=O)CNCCNS(=O)(=O)c1nnc(-c2ccccc2)s1

Procedure:
The title compound was synthesized by the reaction of N-(2-aminoethyl)-glycine ethyl ester 2HCl with 5-phenyl-1,3,4-thiadiazole-2-sulfonyl chloride as per the procedure of example 1. 1H NMR (500 MHz; DMSO-d6) δ 8.05 (d, 2H), 7.60–7.56 (m, 3H), 4.02 (q, 2H), 3.26 (s, 2H), 3.16 (t, 2H), 2.64 (t, 2H), 1.14 (t, 3H).
Reaction SMILES: [C:1]1([C:7]2[N:8]=[C:9]3[C:15]4[CH:16]=[CH:17][CH:18]=[CH:19][C:14]=4[NH:13][C:12]4[N:20]=[CH:21][CH:22]=[CH:23][C:11]=4[N:10]3[C:24]=2[C:25]2[CH:39]=[CH:38][C:28]([CH2:29][NH:30]C(=O)OC(C)(C)C)=[CH:27][CH:26]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[ClH:40]>ClCCl.O1CCOCC1.CCOCC>[ClH:40].[C:1]1([C:7]2[N:8]=[C:9]3[C:15]4[CH:16]=[CH:17][CH:18]=[CH:19][C:14]=4[NH:13][C:12]4[N:20]=[CH:21][CH:22]=[CH:23][C:11]=4[N:10]3[C:24]=2[C:25]2[CH:26]=[CH:27][C:28]([CH2:29][NH2:30])=[CH:38][CH:39]=2)[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1
Reactant: CC(C)(C)OC(=O)NCc1ccc(-c2c(-c3ccccc3)nc3n2-c2cccnc2Nc2ccccc2-3)cc1
Agent: Cl
Solvent: ClCCl
Solvent: C1COCCO1
Solvent: CCOCC
Product: NCc1ccc(-c2c(-c3ccccc3)nc3n2-c2cccnc2Nc2ccccc2-3)cc1
Temperature: 25 °C
Reaction time: 2 h

Procedure:
To a solution of tert-butyl 4-(2-phenyl-9H-benzo[f]imidazo[1,2-d]pyrido[2,3-b][1,4]diazepin-3-yl)benzylcarbamate (0.100 g) in dichloromethane (4 mL) was added 4.0 M HCl in dioxane (1 mL). The reaction was stirred at room temperature for 2 hours and then diluted with ether (20 mL). The product was removed by filtration under reduced pressure and dried to give (4-(2-phenyl-9H-benzo[f]imidazo[1,2-d]pyrido[2,3-b][1,4]diazepin-3-yl)phenyl)methanamine hydrochloride as a bright yellow solid (0.085 g, 83% based on tris HCl salt). 1H NMR (DMSO-d6) 400 MHz δ 8.67 (br. s, 1 H), 8.42 (br. s, 3H), 8.13-8.10 (m, 1H), 7.98-7.95 (m, 1H), 7.51-7.42 (m, 4H), 7.39-7.38 (m, 1H), 7.35-7.26 (m, 5H), 7.15 (t, J=7.4 Hz, 1H), 6.93-6.90 (m, 1H), 6.78-6.73 (m, 1H), 4.06 (dd, JA=11.3 Hz, JB=5.9 Hz, 2H); LCMS: 416 [M+H]; Calc. for C27H21N5.3.26 HCl.0.12 dioxane.0.16 diethylether: C, 60.66; H, 4.86; N, 12.58. Found C, 60.66; H, 4.99; N, 12.58.
Reaction SMILES: [Br:1][CH:2]([CH3:7])[CH2:3][C:4]([OH:6])=[O:5].FC(F)(F)C(OC(=O)C(F)(F)F)=O.[C:21](O)([CH3:24])([CH3:23])[CH3:22]>O1CCCC1>[C:21]([O:5][C:4](=[O:6])[CH2:3][CH:2]([Br:1])[CH3:7])([CH3:24])([CH3:23])[CH3:22]
Reactant: CC(Br)CC(=O)O
Reactant: CC(C)(C)O
Solvent: C1CCOC1
Solvent: O=C(OC(=O)C(F)(F)F)C(F)(F)F
Product: CC(Br)CC(=O)OC(C)(C)C
Temperature: 25 °C
Reaction time: 8 h

Procedure:
3-{2-[4-(2,6-Dichloro-benzyloxy)-phenyl]-morpholin-4-yl}-butyric acid tert-butyl ester was obtained according to a similar manner. The required 3-bromobutyric acid tert-butyl ester was prepared as follows: To a solution of 3-bromobutyric acid (5.0 mL; 47.0 mmol) in tetrahydrofuran (50 mL) was added dropwise trifluoroacetic anhydride (13.7 mL; 98.7 mmol) at −40° C. After 1 hour at −40° C. tert-butyl alcohol (20 mL) was added. The resulting mixture was allowed to warm to RT and stirred overnight. Subsequently, the reaction mixture was concentrated in vacuo. The residue was treated with 2M aqueous NaOH solution and extracted with Et2O. The organic layer was dried (Na2SO4), and concentrated in vacuo to afford 3-bromobutyric acid tert-butyl ester (6.05 g), which was used as such.
Reaction SMILES: NC(C(O)CCCCC)C(O)=O.[C:13]([NH:16][CH:17]([CH:21]([OH:27])[CH2:22][CH2:23][CH2:24][CH2:25][CH3:26])[C:18](O)=[O:19])(=[O:15])[CH3:14].COC(=O)C(NC(=O)C)C(O)CCCCC.[H-].C([Al+]CC(C)C)C(C)C>CO>[C:13]([NH:16][CH:17]([CH:21]([OH:27])[CH2:22][CH2:23][CH2:24][CH2:25][CH3:26])[CH:18]=[O:19])(=[O:15])[CH3:14]
Reactant: CCCCCC(O)C(NC(C)=O)C(=O)O
Agent: CC(C)C[Al+]CC(C)C
Agent: CCCCCC(O)C(N)C(=O)O
Agent: CCCCCC(O)C(NC(C)=O)C(=O)OC
Solvent: CO
Product: CCCCCC(O)C(C=O)NC(C)=O

Procedure:
Protect the amino function in the 2-amino-3-hydroxyoctanoic acid by conversion thereof to an acetamido function, then esterify the resultant 2-acetamido-3-hydroxyoctanoic acid with methanol; reduce the resultant 2-acetamido-3-hydroxyoctanoic acid methyl ester with di-isobutylaluminum hydride according to known procedures to obtain 2-acetamido-3-hydroxyoctanal.
Reaction SMILES: C(OC([NH:8][C@H:9]1[CH2:14][CH2:13][CH2:12][N:11]([CH2:15][C:16]([O:18][CH2:19][C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)=[O:17])[C:10]1=[O:26])=O)(C)(C)C.[ClH:27]>C(OCC)(=O)C>[ClH:27].[NH2:8][C@H:9]1[CH2:14][CH2:13][CH2:12][N:11]([CH2:15][C:16]([O:18][CH2:19][C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)=[O:17])[C:10]1=[O:26]
Reactant: CC(C)(C)OC(=O)N[C@H]1CCCN(CC(=O)OCc2ccccc2)C1=O
Agent: Cl
Solvent: CCOC(C)=O
Product: N[C@H]1CCCN(CC(=O)OCc2ccccc2)C1=O
Reaction time: 3 h

Procedure:
To a solution of compound 40 (4.00 g, 0.0110 mole) in 10 mL of ethyl acetate at room temperature was added 5N HCl in ethyl acetate (50 mL, freshly prepared, 0.25 mole) in one portion. The solution was stirred for 3 hrs, solvent was evaporated, CH2Cl2 was added and the solvents were reevaporated. The residue was pumped at <1 mm Hg on a vacuum pump for 24 hours to afford 3.37 g (~Quantitative crude yield) of product 41 as a colorless foam. TLC (silica gel; CH2Cl2, methanol, conc. NH4OH: 27:3:1): Rf=0.32.
Reaction SMILES: [C:1]([NH:4][C:5]1[CH:14]=[CH:13][C:8]([C:9]([O:11][CH3:12])=[O:10])=[C:7](O)[C:6]=1[CH2:16][CH2:17][CH2:18][OH:19])(=[O:3])[CH3:2].C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.CCOC(/N=N/C(OCC)=O)=O>C1COCC1>[C:1]([NH:4][C:5]1[CH:14]=[CH:13][C:8]([C:9]([O:11][CH3:12])=[O:10])=[C:7]2[C:6]=1[CH2:16][CH2:17][CH2:18][O:19]2)(=[O:3])[CH3:2]
Reactant: COC(=O)c1ccc(NC(C)=O)c(CCCO)c1O
Agent: CCOC(=O)/N=N/C(=O)OCC
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: C1CCOC1
Product: COC(=O)c1ccc(NC(C)=O)c2c1OCCC2
Temperature: 25 °C
Reaction time: 2 h
Yield: 77.8 %

Procedure:
To a solution of compound 5A (1.80 g, 6.7 mmol) and Ph3P (1.94 g, 7.4 mmol) in THF (30 mL) cooled at 0° C. was added dropwise DEAD (1.17 mL, 7.4 mmol). After addition, the reaction mixture was stirred at rt for 2 h, then concentrated under reduced pressure. The residue was chromatographed (silica gel) eluting with 50% to 100% EtOAc/hexane to furnish the title compound (1.3 g) as a white solid.
Reaction SMILES: [C:1]1([C:7]([C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)=[N:8][NH:9][C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.Br[CH2:23][CH2:24][C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1>>[C:1]1([C:7]([C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)=[N:8][N:9]([CH2:23][CH2:24][C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)[C:10]2[CH:11]=[CH:12][CH:13]=[CH:14][CH:15]=2)[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1
Reactant: BrCCc1ccccc1
Reactant: c1ccc(NN=C(c2ccccc2)c2ccccc2)cc1
Product: c1ccc(CCN(N=C(c2ccccc2)c2ccccc2)c2ccccc2)cc1

Procedure:
General procedure B was used to convert 1-(diphenylmethylene)-2-phenylhydrazine (200 mg, 0.735 mmol; Example 79A) and (2-bromoethyl)benzene (1.29 g, 6.9 mmol; Aldrich) to the title compound: MS (DCI/NH3) m/z 391 (M+H)+.
Reaction SMILES: [C:1]1(=[O:8])[NH:7][CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[CH:9]([N:11]=[C:12]=[O:13])=[CH2:10].[N-]=C=O>C(OCC)(=O)C>[CH:9]([NH:11][C:12]([N:7]1[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2][C:1]1=[O:8])=[O:13])=[CH2:10]
Reactant: O=C1CCCCCN1
Reactant: C=CN=C=O
Agent: [N-]=C=O
Solvent: CCOC(C)=O
Product: C=CNC(=O)N1CCCCCC1=O
Temperature: 50 °C

Procedure:
113 parts of ε-caprolactam and 91 parts of ethyl acetate (+0.015% of dibutyl-tin dilaurate) are introduced into a reaction vessel and the mixture is heated to about 50° C. A mixture of 69 parts of vinyl isocyanate and 91 parts of ethyl acetate is then added dropwise in the course of 1 hour, after which the mixture is allowed to react for 5 hours. A pale yellow clear solution is obtained. Blocked isocyanate content: 11.5%.
Reaction SMILES: [C:1]([NH:5][S:6]([C:9]1[CH:14]=[CH:13][C:12]([N:15]=[CH:16][C:17]2[CH:22]=[CH:21][C:20]([O:23][CH3:24])=[C:19]([F:25])[CH:18]=2)=[CH:11][CH:10]=1)(=[O:8])=[O:7])([CH3:4])([CH3:3])[CH3:2].S([CH2:36][N+:37]#[C-:38])(C1C=CC(C)=CC=1)(=O)=O.C([O-])([O-])=O.[K+].[K+].COCCOC>CO>[C:1]([NH:5][S:6]([C:9]1[CH:10]=[CH:11][C:12]([N:15]2[C:16]([C:17]3[CH:22]=[CH:21][C:20]([O:23][CH3:24])=[C:19]([F:25])[CH:18]=3)=[CH:38][N:37]=[CH:36]2)=[CH:13][CH:14]=1)(=[O:8])=[O:7])([CH3:4])([CH3:3])[CH3:2]
Reactant: [C-]#[N+]CS(=O)(=O)c1ccc(C)cc1
Reactant: COc1ccc(C=Nc2ccc(S(=O)(=O)NC(C)(C)C)cc2)cc1F
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CO
Solvent: COCCOC
Product: COc1ccc(-c2cncn2-c2ccc(S(=O)(=O)NC(C)(C)C)cc2)cc1F
Yield: 90 %

Procedure:
A mixture of N-tert-butyl-4-[(3-fluoro-4-methoxybenzylidene)amino]benzenesulfonamide (41.5 g, 114 mmol, obtained in example 2), tosylmethylisocyanide (33.22 g, 171 mmol), K2CO3 (31.1 g, 228 mmol), DME (340 mL) and MeOH (778 mL) is heated at reflux for 3 h. The solvent is removed and the residue is taken up in a CHCl3/H2O mixture and the layers are separated. The aqueous phase is extracted with CHCl3 and the combined organic extracts are dried over MgSO4 and concentrated. A crude product is obtained, which is washed with Et2O several times to give 41.40 g of a creamy solid that is directly used in the next reaction (yield: 90%).
Reaction SMILES: [CH2:1]([Mg]Cl)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:10]([O:14][C:15](=[O:27])[CH2:16][CH:17]([NH:20][C:21]([O:23][CH2:24][CH:25]=[CH2:26])=[O:22])[CH:18]=[O:19])([CH3:13])([CH3:12])[CH3:11]>C1COCC1>[C:10]([O:14][C:15](=[O:27])[CH2:16][CH:17]([NH:20][C:21]([O:23][CH2:24][CH:25]=[CH2:26])=[O:22])[CH:18]([OH:19])[CH2:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1)([CH3:13])([CH3:12])[CH3:11]
Reactant: C=CCOC(=O)NC(C=O)CC(=O)OC(C)(C)C
Reactant: Cl[Mg]Cc1ccccc1
Solvent: C1CCOC1
Product: C=CCOC(=O)NC(CC(=O)OC(C)(C)C)C(O)Cc1ccccc1
Temperature: 0 °C

Procedure:
To a solution of benzylmagnesium chloride (20 mL, 20 mmol) in THF at −78° C. is added dropwise a 0° C. solution of 3-allyloxycarbonylamino-4-oxo-butyric acid tert-butyl ester, 102, (5.14 g, 20 mmol) in THF (100 mL). Once the addition is complete, the solution is allowed to warm to 0° C. over 30 minutes then the reaction mixture is poured into a beaker of crushed ice. The solution is extracted ×3 with CH2Cl2 (100 mL), the organic layers combined, dried over Na2SO4 and concentrated in vacuo to afford the desired product which is used without further purification.
Reaction SMILES: [CH3:1][C:2]1[CH:7]=[C:6]([OH:8])[C:5]2[O:9][C:10]3[C:15]([C:16]([O:18][CH2:19][C:4]=2[CH:3]=1)=[O:17])=[C:14]([O:20][CH3:21])[C:13]([C@@H:22]([OH:27])[CH2:23][CH:24]([CH3:26])[CH3:25])=[CH:12][CH:11]=3.[Cr](Cl)([O-])(=O)=O.[NH+]1C=CC=CC=1.C(OCC)C>C(Cl)Cl>[OH:8][C:6]1[C:5]2[O:9][C:10]3[CH:11]=[CH:12][C:13]([C:22](=[O:27])[CH2:23][CH:24]([CH3:26])[CH3:25])=[C:14]([O:20][CH3:21])[C:15]=3[C:16](=[O:17])[O:18][CH2:19][C:4]=2[CH:3]=[C:2]([CH3:1])[CH:7]=1
Reactant: COc1c([C@@H](O)CC(C)C)ccc2c1C(=O)OCc1cc(C)cc(O)c1O2
Agent: O=[Cr](=O)([O-])Cl
Agent: c1cc[nH+]cc1
Solvent: ClCCl
Solvent: CCOCC
Product: COc1c(C(=O)CC(C)C)ccc2c1C(=O)OCc1cc(C)cc(O)c1O2

Procedure:
800 mg (2.2 mmol) of penicillide (Ib) are stirred at 25° C. under argon for 3 h in 15 ml of methylene chloride and 880 mg (4.1 mmol) of pyridinium chlorochromate. After addition of 200 ml of diethyl ether, the mixture is filtered through silica gel Si60. The evaporation residue of the filtrate is chromatographed on silica gel using petroleum ether/ether =1:1
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:28]=[CH:27][C:6]([NH:7][C:8]2[CH:20]=[C:19]([C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=3)[CH:18]=[CH:17][C:9]=2[C:10]([O:12]C(C)(C)C)=[O:11])=[CH:5][CH:4]=1>FC(F)(F)C(O)=O>[CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]([NH:7][C:8]2[CH:20]=[C:19]([C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=3)[CH:18]=[CH:17][C:9]=2[C:10]([OH:12])=[O:11])=[CH:27][CH:28]=1
Reactant: COc1ccc(Nc2cc(-c3ccccc3)ccc2C(=O)OC(C)(C)C)cc1
Solvent: O=C(O)C(F)(F)F
Product: COc1ccc(Nc2cc(-c3ccccc3)ccc2C(=O)O)cc1
Temperature: 25 °C
Reaction time: 2 h

Procedure:
Trifluoroacetic acid 10 mL was added to the obtained tert-butyl 2-(4-methoxyanilino)-4-phenylbenzoate, and it was stirred at room temperature for 2 hours. The solvent was removed under reduced pressure,diisopropyl ether was added to the obtained residue, and solid matter was filtrated to give 2-(4-methoxyanilino)-4-phenylbenzoic acid 44 mg of yellow solid.
Reaction SMILES: [CH3:1][C:2]1([CH3:15])[CH2:11][CH2:10][C:9]([CH3:13])([CH3:12])[C:8]2[CH:7]=[C:6]([NH2:14])[CH:5]=[CH:4][C:3]1=2.I[C:17]1[CH:25]=[CH:24][C:20]([C:21]([OH:23])=[O:22])=[CH:19][CH:18]=1.CN1CCOCC1.Cl>O1CCOCC1>[CH3:1][C:2]1([CH3:15])[CH2:11][CH2:10][C:9]([CH3:13])([CH3:12])[C:8]2[CH:7]=[C:6]([NH:14][C:17]3[CH:25]=[CH:24][C:20]([C:21]([OH:23])=[O:22])=[CH:19][CH:18]=3)[CH:5]=[CH:4][C:3]1=2
Reactant: CC1(C)CCC(C)(C)c2cc(N)ccc21
Reactant: O=C(O)c1ccc(I)cc1
Agent: Cl
Solvent: C1COCCO1
Solvent: CN1CCOCC1
Product: CC1(C)CCC(C)(C)c2cc(Nc3ccc(C(=O)O)cc3)ccc21

Procedure:
1.02 g (5 mmol) of 5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthylamine, 1.24 g (5 mmol) of 4-iodobenzoic acid, 820 μl (7.5 mmol) of N-methylmorpholine, 360 mg (2.5 mmol) of Cu2O and 15 ml of dioxane were introduced successively into a round-bottomed flask. The entire contents were heated at reflux for 24 hours, the reaction medium poured into 15 ml of 5N hydrochloric acid, the precipitate filtered and the latter washed with water.
Reaction SMILES: CC1(C)[O:6][C:5](=[CH:7][C:8]([N:10]([CH2:13][C:14]2[CH:19]=[CH:18][C:17]([F:20])=[CH:16][CH:15]=2)[O:11][CH3:12])=[O:9])[C:4](=[O:21])O1.[CH:23]1([CH2:27][S:28]([NH2:31])(=[O:30])=[O:29])[CH2:26][CH2:25][CH2:24]1>>[F:20][C:17]1[CH:16]=[CH:15][C:14]([CH2:13][N:10]([O:11][CH3:12])[C:8](=[O:9])[CH:7]=[C:5]([OH:6])[C:4]([NH:31][S:28]([CH2:27][CH:23]2[CH2:26][CH2:25][CH2:24]2)(=[O:30])=[O:29])=[O:21])=[CH:19][CH:18]=1
Reactant: NS(=O)(=O)CC1CCC1
Reactant: CON(Cc1ccc(F)cc1)C(=O)C=C1OC(C)(C)OC1=O
Product: CON(Cc1ccc(F)cc1)C(=O)C=C(O)C(=O)NS(=O)(=O)CC1CCC1

Procedure:
2-(2,2-Dimethyl-5-oxo-[1,3]dioxolan-4-ylidene)-N-(4-fluoro-benzyl)-N-methoxy-acetamide was treated with cyclobutyl-methanesulfonamide as described in the preparation of compound 1 to yield the title compound. LCMS (M+H) calcd for C17H22FN2O6S: 401.1; found: 401.0. 1H NMR (500 MHz, CDCl3) δ: 1.87 (overlapping m, 3), 1.96 (m, 1), 2.21 (m, 2), 2.86 (heptet, 1, J=8), 3.55 (d, 2, J=7), 3.66 (s, 3), 4.79 (s, 2), 6.53 (s, 1), 7.02 (m, 2), 7.29 (m, 2). 13C NMR (125 MHz, CDCl3) δ: 19.20, 28.12, 30.01, 48.31, 58.99, 63.23, 92.56, 115.72, 115.89, 130.28, 130.35, 131.05, 159.18, 160.12, 161.71, 163.67, 170.87.
Reaction SMILES: [OH:1][C@H:2]1[CH2:19][CH2:18][C@@:17]2([CH3:20])[C@H:4]([CH2:5][CH2:6][C@@H:7]3[C@@H:16]2[CH2:15][CH2:14][C@@:12]2([CH3:13])[C@:8]3([OH:29])[CH2:9][CH2:10][C@@H:11]2/[CH:21]=[CH:22]/[CH:23]=[CH:24]/[C:25](OC)=[O:26])[CH2:3]1>O1CCCC1.[AlH](CC(C)C)CC(C)C.CCCCCC>[OH:1][C@H:2]1[CH2:19][CH2:18][C@@:17]2([CH3:20])[C@H:4]([CH2:5][CH2:6][C@@H:7]3[C@@H:16]2[CH2:15][CH2:14][C@@:12]2([CH3:13])[C@:8]3([OH:29])[CH2:9][CH2:10][C@@H:11]2/[CH:21]=[CH:22]/[CH:23]=[CH:24]/[CH2:25][OH:26])[CH2:3]1
Reactant: COC(=O)/C=C/C=C/[C@H]1CC[C@]2(O)[C@@H]3CC[C@@H]4C[C@@H](O)CC[C@]4(C)[C@H]3CC[C@]12C
Agent: CC(C)C[AlH]CC(C)C
Solvent: C1CCOC1
Solvent: CCCCCC
Product: C[C@]12CC[C@H](O)C[C@H]1CC[C@@H]1[C@@H]2CC[C@]2(C)[C@@H](/C=C/C=C/CO)CC[C@]12O
Temperature: 25 °C
Reaction time: 8 h
Yield: 66.2 %

Procedure:
To a solution of 7.95 g of methyl (E,E)-5-(3β,14β-dihydroxy-5β-androstane-17β-yl)-2,4-pentadienoate (Boutagy J. and Thomas R., Aust. J. Pharm. Chem., 1972, NS1, 67) in 390 ml of dry tetrahydrofuran, 133 ml of 1M i-Bu2AlH in hexane were added dropwise under nitrogen at -78° C. After 2 hrs the reaction was quenched with aqueous sodium sulfate (63 g in 390 ml of water) and stirred at room temperature overnight. The mixture was then filtered through Celite and washed with ethyl acetate. The organic solution was dried over anhydrous sodium sulfate and evaporated to dryness to give 4.90 g of (E,E)-5-(3β,14β-dihydroxy-5β-androstane-17β-yl)-2,4-pentadien-1-ol as an off-white solid.
Reaction SMILES: N1(NC2C=CC=CC=2)C=CN=N1.[N:13]1([C:18]2[CH:19]=[C:20]3[C:24](=[CH:25][CH:26]=2)[NH:23][C:22](=[O:27])[C:21]3=[O:28])[CH:17]=[N:16][CH:15]=[N:14]1.[NH:29]([C:31]1[CH:36]=[CH:35][C:34]([S:37]([NH:40][CH3:41])(=[O:39])=[O:38])=[CH:33][CH:32]=1)[NH2:30]>>[N:13]1([C:18]2[CH:19]=[C:20]3[C:24](=[CH:25][CH:26]=2)[NH:23][C:22](=[O:27])[C:21]3=[O:28])[CH:17]=[N:16][CH:15]=[N:14]1.[CH3:41][NH:40][S:37]([C:34]1[CH:33]=[CH:32][C:31]([NH:29][N:30]=[C:21]2[C:20]3[C:24](=[CH:25][CH:26]=[C:18]([N:13]4[CH:17]=[N:16][CH:15]=[N:14]4)[CH:19]=3)[NH:23][C:22]2=[O:27])=[CH:36][CH:35]=1)(=[O:39])=[O:38]
Reactant: CNS(=O)(=O)c1ccc(NN)cc1
Agent: O=C1Nc2ccc(-n3cncn3)cc2C1=O
Agent: c1ccc(Nn2ccnn2)cc1
Product: CNS(=O)(=O)c1ccc(NN=C2C(=O)Nc3ccc(-n4cncn4)cc32)cc1

Procedure:
5-[1,2,4]Triazol-1-yl-1H-indole-2,3-dione was prepared from 4-11,2,4]-triazol-1-yl-phenylamine according to Procedure A in 6% yield: 1H NMR (DMSO-d6): δ 7.04 (d, J=8.4 Hz, 1H), 7.97 (d, J=2.2 Hz, 1H), 8.01 (dd, J=2.2, 8.4 Hz, 1H), 8.20 (s, 1H), 9.26 (s, 1H), 11.19 (bs, 1H); APCI−MS m/z 215 (M+1)+. Condensation of 5-[1,2,4]triazol-1-yl-1H-indole-2,3-dione with 4-hydrazino-N-methyl-phenylsulfonamide according to Procedure G gave the title compound in 86% yield: 1H NMR (DMSO-d6): δ 2.38 (d, J=5.0 Hz, 3H), 7.05 (d, J=8.4 Hz, 1H), 7.30 (q, J=5.0 Hz, 1H), 7.65 (d, J=8.7 Hz, 2H), 7.72 (d, J=8.7 Hz, 3H), 8.01 (s, 1H), 8.20 (s, 1H), 9.23 (s, 1H), 11.27 (s, 1H), 12.80 (s, 1H); Anal. Calcd for C16H15N7O3S.1.3 H2O: C, 48.52, H, 4.22; N, 23.30; S, 7.62. Found C, 48.53, H, 4.25; N, 23.17; S, 7.55.
Reaction SMILES: C[O:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]2[N:10]([C:23]3[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=3)[C:11]([C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=3)=[CH:12][C:13](=[O:16])[C:14]=2[CH3:15])=[CH:5][CH:4]=1.C(Cl)Cl.B(Br)(Br)Br.B(Cl)(Cl)Cl>C(Cl)(Cl)Cl.C1C=CC=CC=1>[OH:2][C:3]1[CH:4]=[CH:5][C:6]([C:9]2[N:10]([C:23]3[CH:24]=[CH:25][CH:26]=[CH:27][CH:28]=3)[C:11]([C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=3)=[CH:12][C:13](=[O:16])[C:14]=2[CH3:15])=[CH:7][CH:8]=1
Reactant: COc1ccc(-c2c(C)c(=O)cc(-c3ccccc3)n2-c2ccccc2)cc1
Agent: BrB(Br)Br
Agent: ClB(Cl)Cl
Solvent: ClC(Cl)Cl
Solvent: c1ccccc1
Solvent: ClCCl
Product: Cc1c(-c2ccc(O)cc2)n(-c2ccccc2)c(-c2ccccc2)cc1=O

Procedure:
For example, when 2-(4-methoxyphenyl)-3-methyl-1,6-diphenyl-4(1H)-pyridinone is either dissolved or suspended in a suitable solvent, e.g., methylene chloride, benzene or chloroform, and a Lewis acid such as boron tribromide, boron trichloride or the like is then added to the resulting solution to conduct a reaction, 2-(4-hydroxyphenyl)-3-methyl-1,6-diphenyl-4(1H)-pyridinone is produced.
Reaction SMILES: [CH:1]1([N:6]2[CH2:12][C:11]([F:14])([F:13])[C:10](=[O:15])[N:9]([CH3:16])[C:8]3[CH:17]=[N:18][C:19]([NH:21][C:22]4[CH:30]=[CH:29][C:25]([C:26]([OH:28])=O)=[CH:24][C:23]=4[O:31][CH2:32][CH3:33])=[N:20][C:7]2=3)[CH2:5][CH2:4][CH2:3][CH2:2]1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[CH3:58][N:59]1[CH2:64][CH2:63][CH:62]([NH2:65])[CH2:61][CH2:60]1>>[CH:1]1([N:6]2[CH2:12][C:11]([F:13])([F:14])[C:10](=[O:15])[N:9]([CH3:16])[C:8]3[CH:17]=[N:18][C:19]([NH:21][C:22]4[CH:30]=[CH:29][C:25]([C:26]([NH:65][CH:62]5[CH2:63][CH2:64][N:59]([CH3:58])[CH2:60][CH2:61]5)=[O:28])=[CH:24][C:23]=4[O:31][CH2:32][CH3:33])=[N:20][C:7]2=3)[CH2:2][CH2:3][CH2:4][CH2:5]1
Reactant: CN1CCC(N)CC1
Reactant: CCOc1cc(C(=O)O)ccc1Nc1ncc2c(n1)N(C1CCCC1)CC(F)(F)C(=O)N2C
Agent: CN(C)C(On1nnc2cccnc21)=[N+](C)C
Agent: F[P-](F)(F)(F)(F)F
Product: CCOc1cc(C(=O)NC2CCN(C)CC2)ccc1Nc1ncc2c(n1)N(C1CCCC1)CC(F)(F)C(=O)N2C

Procedure:
The title compound was synthesized from 4-(9-cyclopentyl-7,7-difluoro-5-methyl-6-oxo-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b][1,4]diazepin-2-ylamino)-3-ethoxybenzoic acid as described in the General procedure for amide bond synthesis using HATU and 1-methylpiperidin-4-amine. The final compound was purified by reverse phase HPLC and basified to give the free base. 1H NMR (400 MHz, DMSO-d6) δ ppm 1.41 (t, J=6.7 Hz, 3H) 1.60 (m, 6H) 1.74 (m, 4H) 1.95 (m, 4H) 2.18 (s, 3H) 2.79 (d, J=10.6 Hz, 2H) 3.73 (m, 1H) 4.05 (t, J=13.9 Hz, 2H) 4.19 (d, J=7.1 Hz, 2H) 4.74 (m, 1H) 7.40-7.59 (m, 2H) 7.91 (s, 1H) 8.11 (d, J=7.6 Hz, 1H) 8.26 (m, 2H). [M+H] calc'd for C28H37F2N7O3, 558. found 558.
Reaction SMILES: [NH2:1][C:2]1[CH:10]=[CH:9][C:5]2[NH:6][N:7]=[N:8][C:4]=2[CH:3]=1.[C:11](Cl)(=[O:15])[C:12]([CH3:14])=[CH2:13]>C(#N)C.N1C=CC=CC=1>[C:11]([NH:1][C:2]1[CH:10]=[CH:9][C:5]2[NH:6][N:7]=[N:8][C:4]=2[CH:3]=1)(=[O:15])[C:12]([CH3:14])=[CH2:13]
Reactant: C=C(C)C(=O)Cl
Reactant: Nc1ccc2[nH]nnc2c1
Solvent: c1ccncc1
Solvent: CC#N
Product: C=C(C)C(=O)Nc1ccc2[nH]nnc2c1
Reaction time: 0.5 h

Procedure:
After 26.8 g of 5-aminobenzotriazole was dissolved in a mixture of acetonitrile (300 ml) and pyridine (40 ml), 46.5 g of methacrylic acid chloride was added dropwise. The resulting solution was concentrated and 200 ml of a 10% aqueous solution of sodium hydroxide was added. After the mixture was agitated for 30 minutes, it was neutralized with dilute hydrochloric acid and the end compound was obtained as a solid precipitate in an amount of 27.3 g (yield, 6.7%).
Reaction SMILES: C[O:2][C:3]1[C:8]2[C:9]([C:18]3[CH:23]=[CH:22][C:21]([CH2:24][C:25]#[N:26])=[CH:20][CH:19]=3)=[CH:10][N:11]([CH:12]([CH2:16][CH3:17])[CH2:13][O:14][CH3:15])[C:7]=2[CH:6]=[CH:5][N:4]=1.[I-].[Na+].Cl[Si](C)(C)C.C(=O)([O-])O.[Na+]>C(#N)C>[CH3:15][O:14][CH2:13][CH:12]([N:11]1[C:7]2[CH:6]=[CH:5][NH:4][C:3](=[O:2])[C:8]=2[C:9]([C:18]2[CH:19]=[CH:20][C:21]([CH2:24][C:25]#[N:26])=[CH:22][CH:23]=2)=[CH:10]1)[CH2:16][CH3:17]
Reactant: CCC(COC)n1cc(-c2ccc(CC#N)cc2)c2c(OC)nccc21
Agent: C[Si](C)(C)Cl
Agent: O=C([O-])O
Agent: [I-]
Solvent: CC#N
Product: CCC(COC)n1cc(-c2ccc(CC#N)cc2)c2c(=O)[nH]ccc21
Temperature: 50 °C
Reaction time: 8 h
Yield: 67.1 %

Procedure:
To a solution of (4-(4-methoxy-1-(1-methoxybutan-2-yl)-1H-pyrrolo[3,2-c]pyridin-3-yl)phenyl)acetonitrile (18.0 mg) in acetonitrile (2 mL) were added sodium iodide (19.3 mg) and chloro(trimethyl)silane (0.065 mL), and the mixture was stirred overnight at 50° C. To the reaction mixture was added saturated aqueous sodium hydrogencarbonate solution, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (basic silica gel, ethyl acetate to ethyl acetate/methanol) to give the title compound (11.6 mg).
Reaction SMILES: [N+:1]([C:4]1[CH:11]=[CH:10][C:7]([CH2:8]O)=[CH:6][C:5]=1[O:12][CH3:13])([O-:3])=[O:2].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[C:33]1(=[O:43])[NH:37][C:36](=[O:38])[C:35]2=[CH:39][CH:40]=[CH:41][CH:42]=[C:34]12>C1COCC1>[CH3:13][O:12][C:5]1[CH:6]=[C:7]([CH:10]=[CH:11][C:4]=1[N+:1]([O-:3])=[O:2])[CH2:8][N:37]1[C:33](=[O:43])[C:34]2[C:35](=[CH:39][CH:40]=[CH:41][CH:42]=2)[C:36]1=[O:38]
Reactant: COc1cc(CO)ccc1[N+](=O)[O-]
Reactant: O=C1NC(=O)c2ccccc21
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: C1CCOC1
Product: COc1cc(CN2C(=O)c3ccccc3C2=O)ccc1[N+](=O)[O-]
Temperature: 25 °C
Yield: 80.3 %

Procedure:
To a 250 mL round bottomed flask containing 10 g (55 mmol) of 4-nitro-3-methoxybenzyl alcohol in 150 mL THF was added, diethylazodiacarboxylate (8.03 g, 54.6 mmol, 1 eq.) and triphenylphosphine (15.0 g, 57.3 mmol) followed by 11.6 g of phthalimide (57.3 mmol) at 0° C. Reaction was then allowed to gradually warm to room temperature over night. A white precipitate formed and was collected by suction filtration. Recrystallization from acetonitrile gave 13.8 g (81%) of the desired product. 1H NMR (400 MHz, d6-DMSO): δ 7.79 (m, 5H), 7.19 (s, 1H), 7.08 (d, J=8.80 Hz, 1H), 4.91 (s, 2H), 3.87 (s, 3H).