Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [O-]S(C(F)(F)F)(=O)=O.[Yb+3].[O-]S(C(F)(F)F)(=O)=O.[O-]S(C(F)(F)F)(=O)=O.[NH2:26][C:27]1[C:28]([C:37]#[N:38])=[N:29][C:30]([Cl:36])=[C:31](N)[C:32]=1CC>C(OCC)(OCC)OCC>[Cl:36][C:30]1[N:29]=[C:28]([C:37]#[N:38])[C:27]2[N:26]=[CH:28][N:29]([CH2:30][CH3:31])[C:32]=2[CH:31]=1
Reactant: CCc1c(N)c(Cl)nc(C#N)c1N
Agent: O=S(=O)([O-])C(F)(F)F
Agent: [Yb+3]
Solvent: CCOC(OCC)OCC
Product: CCn1cnc2c(C#N)nc(Cl)cc21
Temperature: 120 °C
Reaction time: 2.5 h
Yield: 131.3 %

Procedure:
Ytterbium triflate (75 mg) was added to a solution of 3-amino-6-chloro-4-ethyl-amino-pyridine-2-carbonitrile (1.41 g) in triethyl orthoformate (50 mL). The mixture was heated at 120° C. under stirring for 2.5 hours, than concentrated under reduced pressure. The residue was chromatographed (eluent: dichloromethane/ethyl acetate 9/1) to yield a solid which was triturated with diethyl ether and filtered off to afford the title compound (0.973 g, 66%) as white crystals (mp=138° C.). 1H NMR (CDCl3) δ: 8.17 (s, 1H); 7.62 (s, 1H); 4.31 (q, J=8 Hz, 2H); 1.62 (t, J=8 Hz, 3H). 13C NMR (CDCl3) δ: 147.5, 143.8, 142.9, 141.7, 124.0, 114.1, 109.2, 40.9, 15.2.
Reaction SMILES: C[O-].[Na+].Cl.[F:5][C:6]1[CH:18]=[CH:17][C:9]([CH2:10][CH:11]2[CH2:16][CH2:15][NH:14][CH2:13][CH2:12]2)=[CH:8][CH:7]=1.C(=O)([O-])[O-].[K+].[K+].Br[CH2:26][C:27]([C:29]1[CH:34]=[CH:33][C:32]([Cl:35])=[CH:31][CH:30]=1)=[O:28]>C(O)C>[F:5][C:6]1[CH:7]=[CH:8][C:9]([CH2:10][CH:11]2[CH2:12][CH2:13][N:14]([CH2:26][C:27]([C:29]3[CH:34]=[CH:33][C:32]([Cl:35])=[CH:31][CH:30]=3)=[O:28])[CH2:15][CH2:16]2)=[CH:17][CH:18]=1
Reactant: Fc1ccc(CC2CCNCC2)cc1
Reactant: O=C(CBr)c1ccc(Cl)cc1
Agent: C[O-]
Agent: Cl
Agent: O=C([O-])[O-]
Solvent: CCO
Product: O=C(CN1CCC(Cc2ccc(F)cc2)CC1)c1ccc(Cl)cc1
Reaction time: 0.25 h

Procedure:
78 ml of ethanol are placed in a 250 ml conical flask and 2 ml of a 5.3N methanolic solution of sodium methoxide are added. 2.29 g (0.01 mol) of 4-(4-fluorobenzyl)-piperidine hydrochloride are added and the mixture is stirred for 15 minutes. 1.38 g of potassium carbonate are then added, followed by 2.33 g (0.01 mol) of 2-bromo-4'-chloroacetophenone, and the mixture is heated under reflux for 2 hours. It is left to cool, the inorganic precipitate is filtered off, the filtrate is evaporated to dryness and the residual oil is taken up in 1N hydrochloric acid. Extraction is carried out with chloroform and the organic phase is washed with water, dried over sodium sulphate and evaporated to dryness. 3.22 g of the crude hydrochloride remain in the form of an oil, which is used as such but which can be recrystallized from a mixture of acetone/diethyl ether (melting point=168° C.).
Reaction SMILES: C[O:2][C:3]([C:5]1[S:6][C:7]([C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)=[CH:8][C:9]=1[N:10]([C:21]([CH3:24])([CH3:23])[CH3:22])[C:11](=[O:20])[C:12]1[CH:17]=[CH:16][C:15]([Cl:18])=[CH:14][C:13]=1[Cl:19])=[O:4].[Li+].[OH-]>C1COCC1.CO.O>[C:21]([N:10]([C:11](=[O:20])[C:12]1[CH:17]=[CH:16][C:15]([Cl:18])=[CH:14][C:13]=1[Cl:19])[C:9]1[CH:8]=[C:7]([C:25]2[CH:26]=[CH:27][CH:28]=[CH:29][CH:30]=2)[S:6][C:5]=1[C:3]([OH:4])=[O:2])([CH3:24])([CH3:22])[CH3:23]
Reactant: COC(=O)c1sc(-c2ccccc2)cc1N(C(=O)c1ccc(Cl)cc1Cl)C(C)(C)C
Agent: [Li+]
Agent: [OH-]
Solvent: CO
Solvent: O
Solvent: C1CCOC1
Product: CC(C)(C)N(C(=O)c1ccc(Cl)cc1Cl)c1cc(-c2ccccc2)sc1C(=O)O
Temperature: 25 °C
Reaction time: 3 h
Yield: 29.7 %

Procedure:
3-[tert-Butyl-(2,4-dichloro-benzoyl)-amino]-5-phenyl-thiophene-2-carboxylic acid methyl ester (112 mg, 0.24 mmol) was dissolved in a mixture of THF-MeOH—H2O (3:2:1) (15 mL) and then 1.5 ml of LiOH 1N was added to it. After 3 h of stirring at room temperature, solvent was removed and then partitioned between 15 ml of H2O, 4 ml of KHSO4 5% and 15 ml of EtOAc. The organic layer was separated and the aqueous phase was washed twice with ethyl acetate (2×10 mL). The combined ethyl acetate layer was dried (MgSO4), concentrated and the residue was purified by preparative chromatography (10% MeOH/CH2Cl2) to obtain 32 mg (29%) of 3-[tert-Butyl-(2,4-dichloro-benzoyl)-amino]-5-phenyl-thiophene-2-carboxylic acid. NMR 1H (DMSO, 400 MHz): 7.62 ppm (d, 2H, Haro); 7.44-7.34 ppm (m, 4H, Haro); 7.32-7.12 ppm (m, 3H, Haro); 2.48 ppm (s, 9H).
Reaction SMILES: [CH3:1][O:2][C:3](=[O:15])[CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][C:12]([OH:14])=O.C(N(CC)CC)C.[C:23]([O:27][C:28](=[O:31])[NH:29][NH2:30])([CH3:26])([CH3:25])[CH3:24]>O1CCCC1>[CH3:1][O:2][C:3](=[O:15])[CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][C:12]([NH:30][NH:29][C:28]([O:27][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:31])=[O:14]
Reactant: CC(C)(C)OC(=O)NN
Reactant: COC(=O)CCCCCCCCC(=O)O
Solvent: CCN(CC)CC
Solvent: C1CCOC1
Product: COC(=O)CCCCCCCCC(=O)NNC(=O)OC(C)(C)C
Temperature: 25 °C
Reaction time: 2 h

Procedure:
10.81 g (50 mmol) of sebacic acid monomethyl ester is dissolved in tetrahydrofuran and successively mixed with 8.32 ml (60 mmol) of triethylamine and 5.28 ml (55 mmol) of chloroformic acid ethyl ester [ethyl chloroformate] at -5° C.. After 15 minutes 6.61 g (50 mmol) of tert-butylcarbazate in tetrahydrofuran is instilled at this temperature and then stirred at room temperature for 2 hours. The precipitate is suctioned off, the filtrate is concentrated by evaporation and taken up in ethyl acetate. The organic phase is successively washed with NaHCO3 solution, citric acid and water and dried on Na2SO4. The oil obtained after concentration by evaporation of the ethyl acetate is chromatographed on silica gel in diisopropyl ether.
Reaction SMILES: [C:1]([N:5]1[C:9](=[O:10])[C:8](Cl)=[C:7]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[S:6]1(=[O:19])=[O:18])([CH3:4])([CH3:3])[CH3:2].[N:20]1([C:27]2[CH:32]=[CH:31][C:30]([NH2:33])=[CH:29][CH:28]=2)[CH2:26][CH2:25][CH2:24][CH2:23][CH2:22][CH2:21]1>CC#N>[N:20]1([C:27]2[CH:28]=[CH:29][C:30]([NH:33][C:8]3[C:9](=[O:10])[N:5]([C:1]([CH3:4])([CH3:3])[CH3:2])[S:6](=[O:19])(=[O:18])[C:7]=3[C:12]3[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=3)=[CH:31][CH:32]=2)[CH2:26][CH2:25][CH2:24][CH2:23][CH2:22][CH2:21]1
Reactant: Nc1ccc(N2CCCCCC2)cc1
Reactant: CC(C)(C)N1C(=O)C(Cl)=C(c2ccccc2)S1(=O)=O
Solvent: CC#N
Product: CC(C)(C)N1C(=O)C(Nc2ccc(N3CCCCCC3)cc2)=C(c2ccccc2)S1(=O)=O
Temperature: 120 °C
Yield: 53.4 %

Procedure:
A mixture of 2-tert-butyl-4-chloro-5-phenylisothiazol-3(2H)-one 1,1-dioxide (0.150 g, 0.500 mmol), (4-azepan-1-ylphenyl)amine (0.095 g, 0.500 mmol) and TEA (0.070 ml, 0.500 mmol) in MeCN (2 ml) was heated in a microwave reactor at 120° C. for 65 mins. TEA (0.070 ml, 0.500 mol) was added and the reaction mixture was heated in a microwave reactor at 120° C. for 15 mins. The reaction mixture was filtered and the residue was purified by silica gel column chromatography using 15-20% EtOAc in petroleum ether 40-60° C. as eluent, to give the title compound (0.121 g, 53%). 1H NMR (500 MHz CDCl3): δ 7.16-7.04 (m, 5H), 7.00 (s, 1H), 6.53 (d, 2H), 6.23 (d, 2H), 3.33 (t, 4H), 1.77 (s, 9H), 1.73-1.61 (m, 4H), 1.50-1.45 (m, 4H); 13C NMR (125 MHz CDCl3): δ 160.4, 146.6, 131.8, 129.8, 128.5, 127.9, 125.4, 124.5, 124.3, 110.7, 108.3, 61.8, 49.7, 27.9, 27.3, 26.9; Mass Spectrum: M+H+ 454.
Reaction SMILES: [N+:1]([C:4]1[CH:9]=[CH:8][C:7]([N:10]2[C:14]([CH2:15]O)=[CH:13][C:12]([C:17]([F:20])([F:19])[F:18])=[N:11]2)=[CH:6][CH:5]=1)([O-:3])=[O:2].C(N(S(F)(F)[F:27])CC)C>C(Cl)Cl>[F:27][CH2:15][C:14]1[N:10]([C:7]2[CH:8]=[CH:9][C:4]([N+:1]([O-:3])=[O:2])=[CH:5][CH:6]=2)[N:11]=[C:12]([C:17]([F:20])([F:19])[F:18])[CH:13]=1
Reactant: O=[N+]([O-])c1ccc(-n2nc(C(F)(F)F)cc2CO)cc1
Reactant: CCN(CC)S(F)(F)F
Solvent: ClCCl
Product: O=[N+]([O-])c1ccc(-n2nc(C(F)(F)F)cc2CF)cc1
Temperature: 0 °C
Reaction time: 0.5 h
Yield: 81 %

Procedure:
Intermediate 19 (0.5 g, 1.75 mmol) was dissolved in DCM (10 ml) and reaction mixture cooled to 0° C. To this (Diethylamino)sulphur trifluoride (0.46 ml, 3.5 mmol) was added drop-wise and allowed the reaction mixture to stir at rt for 30 mins. After completion of the reaction, reaction mixture diluted with DCM and washed with water. DCM removed on rotavapour to obtain the crude. Crude was purified by column chromatography using EA and petether (7:97) as eluent to afford the title compound (0.41 g) as an yellow solid. 1H-NMR (δ ppm, CDCl3, 400 MHz): 8.42 (d, J 9, 2H), 7.86 (d, J 9, 2H), 6.94 (d, J 3.4, 1H), 5.42 (d, J 48.4, 2H).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]2[S:10][C:9](C(O)=O)=[N:8][C:7]=2[C:14]=1[N+:15]([O-:17])=[O:16]>ClCCl>[CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]2[S:10][CH:9]=[N:8][C:7]=2[C:14]=1[N+:15]([O-:17])=[O:16]
Reactant: COc1ccc2sc(C(=O)O)nc2c1[N+](=O)[O-]
Solvent: ClCCl
Product: COc1ccc2scnc2c1[N+](=O)[O-]
Temperature: 60 °C
Yield: 80 %

Procedure:
3 g (11.8 mmol) of 5-methoxy-4-nitro-1,3-benzothiazole-2-carboxylic acid is suspended in 200 ml of dichloromethane and heated at 60° C. for 2 hours. The dichloromethane is evaporated off under reduced pressure. 5-methoxy-4-nitro-1,3-benzothiazole is obtained in the form of a beige powder. (m=2 g; yield=80%).
Reaction SMILES: [CH3:1][N:2]1[C:10]2[C:5](=[CH:6][CH:7]=[C:8]([C:11]3[CH:16]=[CH:15][C:14]([C:17]([F:20])([F:19])[F:18])=[CH:13][CH:12]=3)[CH:9]=2)[CH:4]=[CH:3]1.C([Li])CCC.[C:26](=[O:28])=[O:27]>C1COCC1>[CH3:1][N:2]1[C:10]2[C:5](=[CH:6][CH:7]=[C:8]([C:11]3[CH:12]=[CH:13][C:14]([C:17]([F:18])([F:19])[F:20])=[CH:15][CH:16]=3)[CH:9]=2)[C:4]([C:26]([OH:28])=[O:27])=[CH:3]1
Reactant: O=C=O
Reactant: Cn1ccc2ccc(-c3ccc(C(F)(F)F)cc3)cc21
Agent: [Li]CCCC
Solvent: C1CCOC1
Product: Cn1cc(C(=O)O)c2ccc(-c3ccc(C(F)(F)F)cc3)cc21
Temperature: -78 °C
Reaction time: 0.5 h

Procedure:
To a solution of 1-methyl-6-(4-trifluoromethyl-phenyl)-1H-indole (0.483 g, 1.75 mmol) in dry THF (10 mL) at −78° C. was added n-butyllithium (0.84 mL, 2.1 mmol). The reaction mixture was stirred under nitrogen at −78° C. for 30 minutes then at −50 to −40° C. for 30 minutes. It reaction temperature was cooled to −78° C. and crushed dry ice (3.5 g, 80 mmol) was added. The reaction mixture was stirred overnight at room temperature. It was then concentrated and partitioned in 2N hydrochloric acid and ethyl acetate. The organic phase was washed with water and brine, dried over anhydrous magnesium sulfate and evaporated to dryness. The residue was purified by flash chromatography using 10-50% ethyl aceate in hexane as an eluant. The title compound was obtained as a yellow solid (0.108 g, 19%), mp: 237-239° C. (dec). Mass spectrum (−APCI, [M−H]−) m/z 318. 1HNMR (400 MHz, DMSO-d6): δ12.8-13.2 (br s, 1H), 8.0 (d, 2H, J=8.1 Hz), 7.95 (s, 1H), 7.75-7.85 (m, 3H), 7.5 (dd, 1H, J=8.3 and 1.5 Hz), 7.25 (s, 1H), and 4.10 ppm (s, 3H). Elemental Analysis for C17H12F3NO2: Calculated: C, 63.95; H, 3.79; N, 4.39. Found: C, 63.86; H, 3.55; N, 4.34.
Reaction SMILES: C[O:2][C:3](=[O:32])[CH2:4][CH2:5][C:6]1[CH:11]=[CH:10][C:9]([O:12][CH2:13][C:14]2[O:18][C:17]([C:19]3[CH:24]=[CH:23][C:22]([C:25]([F:28])([F:27])[F:26])=[CH:21][CH:20]=3)=[N:16][C:15]=2[CH2:29][CH3:30])=[CH:8][C:7]=1[CH3:31].[OH-].[Na+].C1COCC1>CO>[CH2:29]([C:15]1[N:16]=[C:17]([C:19]2[CH:20]=[CH:21][C:22]([C:25]([F:26])([F:27])[F:28])=[CH:23][CH:24]=2)[O:18][C:14]=1[CH2:13][O:12][C:9]1[CH:10]=[CH:11][C:6]([CH2:5][CH2:4][C:3]([OH:32])=[O:2])=[C:7]([CH3:31])[CH:8]=1)[CH3:30]
Reactant: CCc1nc(-c2ccc(C(F)(F)F)cc2)oc1COc1ccc(CCC(=O)OC)c(C)c1
Agent: [Na+]
Agent: [OH-]
Solvent: C1CCOC1
Solvent: CO
Product: CCc1nc(-c2ccc(C(F)(F)F)cc2)oc1COc1ccc(CCC(=O)O)c(C)c1

Procedure:
3-{4-[4-Ethyl-2-(4-trifluoromethyl-phenyl)-oxazol-5-ylmethoxy]-2-methyl-phenyl}-propionic acid methyl ester (0.100 g, 0.223 mmole) is treated with a mixture of NaOH(aq) (1 mL)/THF (3 mL)/MeOH (3 mL) at room temperature overnight. The organic solvents are removed on rota-vapor. The residue is diluted with water (10 mL), acidified to pH=2 with 6N HCl(aq). The precipitate is collected through filtration, washed with cold water (30 mL) and dried to provide the titled compound as a white solid. Mass [EI+] 434 (M++H), 432 (M+−H).
Reaction SMILES: [F:1][C:2]([F:23])([F:22])[C:3]1[CH:17]=[C:16]([C:18]([F:21])([F:20])[F:19])[CH:15]=[CH:14][C:4]=1[CH2:5][N:6]1[CH2:11][CH2:10][CH:9]([CH:12]=O)[CH2:8][CH2:7]1.[F:24][C:25]1([F:39])[CH2:30][C@@H:29]([NH:31][C:32]2[CH2:36][S:35][C:34](=[O:37])[N:33]=2)[C@H:28]([OH:38])[CH2:27][CH2:26]1.C([O-])(=O)C.[NH2+]1CCCCC1>CC(O)C>[F:23][C:2]([F:1])([F:22])[C:3]1[CH:17]=[C:16]([C:18]([F:21])([F:20])[F:19])[CH:15]=[CH:14][C:4]=1[CH2:5][N:6]1[CH2:11][CH2:10][CH:9](/[CH:12]=[C:36]2/[C:32]([NH:31][C@@H:29]3[CH2:30][C:25]([F:24])([F:39])[CH2:26][CH2:27][C@H:28]3[OH:38])=[N:33][C:34](=[O:37])[S:35]/2)[CH2:8][CH2:7]1
Reactant: O=C1N=C(N[C@@H]2CC(F)(F)CC[C@H]2O)CS1
Reactant: O=CC1CCN(Cc2ccc(C(F)(F)F)cc2C(F)(F)F)CC1
Agent: C1CC[NH2+]CC1
Agent: CC(=O)[O-]
Solvent: CC(C)O
Product: O=C1N=C(N[C@@H]2CC(F)(F)CC[C@H]2O)/C(=C/C2CCN(Cc3ccc(C(F)(F)F)cc3C(F)(F)F)CC2)S1
Temperature: 75 °C
Reaction time: 8 h
Yield: 71.9 %

Procedure:
To a solution of 1-[2,4-bis(trifluoromethyl)benzyl]piperidine-4-carbaldehyde (777 mg) in 2-propanol (5 mL) were added 4-[trans-(5,5-difluoro-2-hydroxycyclohexyl)amino]-1,3-thiazol-2(5H)-one (860 mg) and piperidinium acetate (339 mg). The reaction mixture was stirred at 75° C. overnight, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate/hexane) and silica gel column chromatography (NH, methanol/ethyl acetate) to give the title compound (941 mg).
Reaction SMILES: [Li+].[OH-].[O:3]=[C:4]1[N:10]([CH:11]2[CH2:16][CH2:15][N:14]([C:17]([O:19][C@@H:20]([C:31]([O:33]C)=[O:32])[CH2:21][C:22]3[CH:27]=[C:26]([CH3:28])[C:25]([Cl:29])=[C:24]([CH3:30])[CH:23]=3)=[O:18])[CH2:13][CH2:12]2)[CH2:9][CH2:8][C:7]2[CH:35]=[CH:36][CH:37]=[CH:38][C:6]=2[NH:5]1>O.C1COCC1>[O:3]=[C:4]1[N:10]([CH:11]2[CH2:16][CH2:15][N:14]([C:17]([O:19][C@@H:20]([C:31]([OH:33])=[O:32])[CH2:21][C:22]3[CH:27]=[C:26]([CH3:28])[C:25]([Cl:29])=[C:24]([CH3:30])[CH:23]=3)=[O:18])[CH2:13][CH2:12]2)[CH2:9][CH2:8][C:7]2[CH:35]=[CH:36][CH:37]=[CH:38][C:6]=2[NH:5]1
Reactant: COC(=O)[C@@H](Cc1cc(C)c(Cl)c(C)c1)OC(=O)N1CCC(N2CCc3ccccc3NC2=O)CC1
Agent: [Li+]
Agent: [OH-]
Solvent: O
Solvent: C1CCOC1
Product: Cc1cc(C[C@@H](OC(=O)N2CCC(N3CCc4ccccc4NC3=O)CC2)C(=O)O)cc(C)c1Cl
Temperature: 25 °C
Reaction time: 1 h

Procedure:
A solution of 150 mg (0.60 mmol) LiOH in 30 mL water was added to a solution of 2.15 g (4.18 mmol) of (R)-2-(4-chloro-3,5-dimethyl-phenyl)-1-methoxycarbonyl-ethyl 4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidine-1-carboxylate in 60 mL THF and the reaction mixture was stirred for 1 h at RT. The mixture was evaporated down in vacuo, the residue was taken up in 100 mL water, acidified with 1 M HCl, the precipitate was filtered and dried in the vacuum drying cupboard at 40° C.
Reaction SMILES: Br[C:2]1[CH:11]=[CH:10][CH:9]=[C:8]2[C:3]=1[CH2:4][CH2:5][CH2:6][C:7]2=[O:12].O.[CH3:14][N:15]1C(=O)CCC1>[C-]#N.[C-]#N.[Zn+2]>[O:12]=[C:7]1[CH2:6][CH2:5][CH2:4][C:3]2[C:2]([C:14]#[N:15])=[CH:11][CH:10]=[CH:9][C:8]1=2
Reactant: CN1CCCC1=O
Reactant: O=C1CCCc2c(Br)cccc21
Agent: [C-]#N
Agent: [Zn+2]
Solvent: O
Product: N#Cc1cccc2c1CCCC2=O
Temperature: 110 °C
Reaction time: 5 h
Yield: 91 %

Procedure:
To a stirred solution of 5-bromo-3,4-dihydronaphthalen-1(2H)-one (9.95 g, 44.2 mmol) in NMP (50 mL) was added Zn(CN)2 (10.38 g, 88.4 mmol). The mixture was degassed twice by bubbling N2 through the solution for 30 min then evacuated. Pd(Ph3)4 (0.5 g, 0.44 mmol) was added and the mixture was heated to 110° C. under N2. After 5 h, the mixture was cooled to room temperature and poured onto ice (600 mL), using water (300 mL) to complete the transfer. After the ice had melted, the solution was filtered and the resulting solid was collected, suspended in DCM, and filtered again. The solid was collected, washed with water, and purified by column chromatography (EA/hex) to provide 6.9 g (91%) of 5-oxo-5,6,7,8-tetrahydronaphthalene-1-carbonitrile INT-1 as a white solid. LCMS-ESI (m/z) calculated for C11H9NO: 171.2; found 172.1 [M+H]+, tR=2.95 min. 1H NMR (400 MHz, CDCl3) δ 8.26 (dd, J=7.9, 1.4 Hz, 1H), 7.82 (dd, J=7.6, 1.4 Hz, 1H), 7.44 (t, J=7.8 Hz, 1H), 3.20 (t, J=6.1 Hz, 2H), 2.72 (dd, J=7.2, 6.1 Hz, 2H), 2.30-2.17 (m, 2H). 13C NMR (101 MHz, CDCl3) δ 196.22, 147.39, 137.18, 133.39, 131.59, 127.19, 116.93, 112.94, 38.48, 28.05, 22.28.
Reaction SMILES: Br[C:2]1[CH:7]=[CH:6][C:5]([CH2:8][CH3:9])=[CH:4][CH:3]=1.[Mg].[B:11](OC)([O:14]C)[O:12]C>CCOCC>[CH2:8]([C:5]1[CH:6]=[CH:7][C:2]([B:11]([OH:14])[OH:12])=[CH:3][CH:4]=1)[CH3:9]
Reactant: CCc1ccc(Br)cc1
Reactant: COB(OC)OC
Agent: [Mg]
Solvent: CCOCC
Product: CCc1ccc(B(O)O)cc1
Temperature: 25 °C
Reaction time: 1.5 h
Yield: 41 %

Procedure:
A solution of 1-bromo-4-ethyl benzene (2.0 g, 11 mmol) in dry ether (5 ml) was added to magnesium turnings (311 mg, 13 mmol), which had been suspended in dry ether, by dropwise addition. After addition was complete, the suspension was refluxed for a period of 15 min, by which time nearly all of the magnesium had reacted. The solution was then added to trimethyl borate (1.12 g, 11 mmol), previously dissolved in ether (5 ml) at −78° C., warmed to room temperature and stirred for 90 min. The reaction was quenched by the addition of 10% aqueous HCl (2 ml) and the solution was extracted with ether. The combined ether extract was extracted with 1 M NaOH (2×20 ml), the aqueous extracts were acidified with dilute HCl to pH 2 and extracted with ether (2×25 ml). The resulting combined ether extract was washed once with water (10 ml), dried and evaporated to produce a white solid (676 mg, 38% yield), m.p. 138-140° C.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:10]=[CH:9][C:6]([CH:7]=O)=[CH:5][CH:4]=1.[C:11]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])(=[O:14])[NH:12][NH2:13]>C1(C)C=CC=CC=1>[CH3:1][O:2][C:3]1[CH:10]=[CH:9][C:6](/[CH:7]=[N:13]/[NH:12][C:11]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])=[CH:5][CH:4]=1
Reactant: CC(C)(C)OC(=O)NN
Reactant: COc1ccc(C=O)cc1
Solvent: Cc1ccccc1
Product: COc1ccc(/C=N/NC(=O)OC(C)(C)C)cc1
Temperature: 60 °C
Yield: 102 %

Procedure:
Add 4-methoxybenzaldehyde (400 g, 2.94 mol) over 20 min to a solution of tert-butyl carbazate (400 g, 2.94 mol) in toluene (750 mL) at 50° C. Heat to reflux over a period of 1 hour (h), collecting water in an azeotrope with the toluene. After no further water is collected, cool to 60° C. Add hexanes until the product precipitates from solution. Cool the bath further to 20° C. Collect the solids by filtration and dry using a nitrogen press to afford the title compound (750.5 g, 91%). 1H NMR [400 MHz, dimethyl sulfoxide-d6 (DMSO-d6)] δ 10.6-10.8 (bs, 1H), 7.88-8.0 (S, 1H), 7.5-7.55 (d, 2H), 6.95-7.0 (d, 2H), 1.45 (s, 9H). ES/MS (m/z): 249 [M-H].
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8](=[O:11])[CH2:9]Cl.[Na+].[I-:13]>CC#N>[NH2:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8](=[O:11])[CH2:9][I:13]
Reactant: [I-]
Reactant: Nc1ccccc1C(=O)CCl
Agent: [Na+]
Solvent: CC#N
Product: Nc1ccccc1C(=O)CI
Temperature: 25 °C
Reaction time: 0.75 h
Yield: 90.5 %

Procedure:
To a solution of 33.11 g (195.21 mM) of 2'-amino-2-chloroacetophenone in 680 ml of CH3CN is added 87.8 g (585.63 mM) of NaI, and the mixture is stirred at room temperature for 45 minutes and concentrated under reduced pressure. The residue is dissolved in ethyl acetate, and the organic layer is washed with aqueous Na2S2O3, and brine in order, dried and concentrated to give 46.1 g (Yield: 90.5%) of 2'-amino-2-iodoacetophenone as crystals.
Reaction SMILES: [CH3:1][O:2][N:3]=[C:4]([C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][C:22]=1Cl)[C:5]([NH:7][C@@H:8]1[C:19](=[O:20])[N:10]2[C@@H:11]([C:16]([OH:18])=[O:17])[C:12]([CH3:15])([CH3:14])[S:13][C@H:9]12)=[O:6].CON=[C:31]([C:48]1N(C)C=C[CH:52]=1)[C:32](N[C@@H]1C(=O)N2[C@@H](C(O)=O)C(C)(C)S[C@H]12)=O.[Na].[K].N(CCO)CCO>>[CH3:1][O:2][N:3]=[C:4]([C:21]1[C:22]2[C:23](=[CH:32][CH:31]=[CH:48][CH:52]=2)[CH:24]=[CH:25][CH:26]=1)[C:5]([NH:7][C@@H:8]1[C:19](=[O:20])[N:10]2[C@@H:11]([C:16]([OH:18])=[O:17])[C:12]([CH3:15])([CH3:14])[S:13][C@H:9]12)=[O:6]
Reactant: CON=C(C(=O)N[C@@H]1C(=O)N2[C@@H]1SC(C)(C)[C@@H]2C(=O)O)c1cccn1C
Reactant: CON=C(C(=O)N[C@@H]1C(=O)N2[C@@H]1SC(C)(C)[C@@H]2C(=O)O)c1ccccc1Cl
Agent: [K]
Agent: [Na]
Solvent: OCCNCCO
Product: CON=C(C(=O)N[C@@H]1C(=O)N2[C@@H]1SC(C)(C)[C@@H]2C(=O)O)c1cccc2ccccc12

Procedure:
6β-[2-methoxyimino-2-(2-chlorophenyl)acetamido]-2,2-dimethylpenam-3α-carboxylic acid, 6β-[2-methoxyimino-2-(1-methylpyrrol-2-yl)acetamido]-2,2-dimethylpenam-3α-carboxylic acid, especially as their sodium, potassium or diethanolamine salts.
Reaction SMILES: [N+:1]([C:4]1[CH:5]=[CH:6][CH:7]=[C:8]2[C:13]=1[N:12]=[CH:11][NH:10][C:9]2=O)([O-:3])=[O:2].P(Cl)(Cl)(Cl)(Cl)[Cl:16]>O=P(Cl)(Cl)Cl>[Cl:16][C:9]1[C:8]2[C:13](=[C:4]([N+:1]([O-:3])=[O:2])[CH:5]=[CH:6][CH:7]=2)[N:12]=[CH:11][N:10]=1
Reactant: O=c1[nH]cnc2c([N+](=O)[O-])cccc12
Reactant: ClP(Cl)(Cl)(Cl)Cl
Solvent: O=P(Cl)(Cl)Cl
Product: O=[N+]([O-])c1cccc2c(Cl)ncnc12
Yield: 91.2 %

Procedure:
A suspension of 8-nitroquinazolin-4(3H)-one (1.0 g, 5.23 mmol) and PCl5 (1.3 g, 6.24 mmol) in POCl3 (5 mL) was heated at reflux for 4 h. Then the reaction mixture was concentrated and the concentrate was diluted with Et2O. The precipitated solid was filtered and dried to afford 1.0 g of the title product. 1H NMR (300 MHz, DMSO d6): δ 9.25 (s, 1H), 8.71 (d, J=7.8 Hz, 1H), 8.59 (d, J=7.8 Hz, 1H), 8.07-8.02 (t, J=7.8 Hz, 1H).
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[C:11](=O)[C:10](=[CH:13]N(C)C)[CH2:9][C:8](=[O:17])[NH:7][C:6]=2[CH:18]=1.[NH:19]([C:23]1[CH:24]=[C:25]([CH:29]=[CH:30][CH:31]=1)[C:26]([OH:28])=[O:27])[C:20]([NH2:22])=[NH:21]>>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[C:11]3[N:21]=[C:20]([NH:19][C:23]4[CH:24]=[C:25]([CH:29]=[CH:30][CH:31]=4)[C:26]([OH:28])=[O:27])[N:22]=[CH:13][C:10]=3[CH2:9][C:8](=[O:17])[NH:7][C:6]=2[CH:18]=1
Reactant: CN(C)C=C1CC(=O)Nc2cc(Cl)ccc2C1=O
Reactant: N=C(N)Nc1cccc(C(=O)O)c1
Product: O=C1Cc2cnc(Nc3cccc(C(=O)O)c3)nc2-c2ccc(Cl)cc2N1

Procedure:
In a manner similar to method I, 8-chloro-4-((dimethylamino)methylene)-3,4-dihydro-1H-benzo[b]azepine-2,5-dione (v-j) and 3-guanidino-benzoic acid were converted to I-62-a (72%): MS m/z=381 (M+H).
Reaction SMILES: C(N[C:10]1[C:23]2[C:22](=[O:24])[C:21]3[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=3)[C:15](=[O:25])[C:14]=2[C:13](Br)=[CH:12][CH:11]=1)(=O)C1C=CC=CC=1.[NH2:27][C:28]1[C:41]2[C:40](=[O:42])[C:39]3[C:34](=[C:35](NC(=O)C4C=CC=CC=4)[CH:36]=[CH:37][CH:38]=3)[C:33](=[O:52])[C:32]=2[CH:31]=[CH:30][CH:29]=1.C(=O)([O-])[O-].[Na+].[Na+].[N+](C1C=CC=CC=1)([O-])=O>[Cu]Cl>[CH:12]1[CH:13]=[C:14]2[C:15]([C:16]3[CH:17]=[CH:18][CH:19]=[C:20]([NH:27][C:28]4[C:41]5[C:40]([C:39]6[C:34]([C:33](=[O:52])[C:32]=5[CH:31]=[CH:30][CH:29]=4)=[CH:35][CH:36]=[CH:37][CH:38]=6)=[O:42])[C:21]=3[C:22](=[O:24])[C:23]2=[CH:10][CH:11]=1)=[O:25]
Reactant: Nc1cccc2c1C(=O)c1cccc(NC(=O)c3ccccc3)c1C2=O
Reactant: O=C(Nc1ccc(Br)c2c1C(=O)c1ccccc1C2=O)c1ccccc1
Agent: Cl[Cu]
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: O=[N+]([O-])c1ccccc1
Product: O=C1c2ccccc2C(=O)c2c(Nc3cccc4c3C(=O)c3ccccc3C4=O)cccc21
Temperature: 190 °C
Reaction time: 2 h

Procedure:
55 parts of 1-benzamido-4-bromoanthraquinone, 45 parts of 1-amino-5-benzamidoanthraquinone, 10 parts of sodium carbonate and 1.4 parts of copper(I) chloride are suspended in 550 parts of nitrobenzene. With stirring, the mixture is heated to 190° C. and then a further 1.3 parts of copper(I) chloride are added. The reaction mixture is heated to 205° C. and stirred for 3 hours at this temperature while distilling off the water of reaction. The batch is then heated to 215° C. and the pressure rises to about 1 bar. Stirring is continued for another 2 hours under these conditions. The reaction mixture is then slightly cooled and the nitrobenzene is removed by distillation. The reaction product is dried, affording about 85 parts of anthrimide, which can be converted into a brown vat dye by carbazolation.