Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: N1C=CC=CC=1.Cl.[CH3:8][NH:9][O:10][CH3:11].[C:12]1([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)[C:13]([C:18](Cl)=[O:19])=[CH:14][CH:15]=[CH:16][CH:17]=1>ClCCl.C(OCC)(=O)C>[CH3:11][O:10][N:9]([CH3:8])[C:18]([C:13]1[C:12]([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)=[CH:17][CH:16]=[CH:15][CH:14]=1)=[O:19]
Reactant: O=C(Cl)c1ccccc1-c1ccccc1
Reactant: CNOC
Agent: Cl
Solvent: c1ccncc1
Solvent: CCOC(C)=O
Solvent: ClCCl
Product: CON(C)C(=O)c1ccccc1-c1ccccc1
Temperature: 25 °C
Reaction time: 2 h
Yield: 73.8 %

Procedure:
The intermediate N-methoxy-N-methyl-p-biphenylcarboxamide was first formed. Pyridine (4 mL, 5 equivalents) and N,O-dimethylhydroxylamine hydrochloride (980 mg, 10 mmol) were added to a solution of p-biphenylcarbonyl chloride (2.16 g, 10 mmol) in dry dichloromethane (10 mL). The solution was stirred for 2 hours at room temperature and then diluted with ethyl acetate (20 mL), washed sequentially with 1N HCl (2×20 mL), saturated sodium bicarbonate (20 mL), and brine (20 mL). It was then dried over magnesium surfate and evaporated under reduced pressure to give N-methoxy-N-methyl-p-biphenylcarboxamide as a solid (1.78 g, 74%). The solid was recrystallized from ethyl acetate/hexane for analysis: mp 77°-78° C. The identity of the solid was confirmed as that of N-methoxy-N-methyl-p-biphenylcarboxamide by IR, proton NMR, 13C NMR and elemental analysis, with mass spectrometric determination of the molecular weight.
Reaction SMILES: [C:1]([O:5][C:6](=[O:26])[NH:7][C:8]1[CH2:9][O:10][CH2:11][CH2:12][C@:13]([C:18]2[CH:23]=[C:22]([NH2:24])[CH:21]=[CH:20][C:19]=2[F:25])([CH:15]([F:17])[F:16])[N:14]=1)([CH3:4])([CH3:3])[CH3:2].[C:27]([C:29]1[CH:30]=[CH:31][C:32]([C:35](O)=[O:36])=[N:33][CH:34]=1)#[N:28].C1C=NC2N(O)N=NC=2C=1.C(Cl)CCl.CCN(C(C)C)C(C)C>CN(C=O)C>[C:1]([O:5][C:6](=[O:26])[NH:7][C:8]1[CH2:9][O:10][CH2:11][CH2:12][C@:13]([C:18]2[CH:23]=[C:22]([NH:24][C:35]([C:32]3[CH:31]=[CH:30][C:29]([C:27]#[N:28])=[CH:34][N:33]=3)=[O:36])[CH:21]=[CH:20][C:19]=2[F:25])([CH:15]([F:17])[F:16])[N:14]=1)([CH3:4])([CH3:2])[CH3:3]
Reactant: CC(C)(C)OC(=O)NC1=N[C@@](c2cc(N)ccc2F)(C(F)F)CCOC1
Reactant: N#Cc1ccc(C(=O)O)nc1
Agent: On1nnc2cccnc21
Solvent: CCN(C(C)C)C(C)C
Solvent: ClCCCl
Solvent: CN(C)C=O
Product: CC(C)(C)OC(=O)NC1=N[C@@](c2cc(NC(=O)c3ccc(C#N)cn3)ccc2F)(C(F)F)CCOC1
Temperature: 25 °C
Yield: 98.2 %

Procedure:
A solution of [(S)-5-(5-amino-2-fluoro-phenyl)-5-difluoromethyl-2,5,6,7-tetrahydro-[1,4]oxazepin-3-yl]-carbamic acid tert-butyl ester (51.2 mg, 0.137 mmol), 5-cyano-2-pyridinecarboxylic acid (30.5 mg, 0.206 mmol) and HOAT (33.6 mg, 0.247 mmol) in 0.6 mL DMF was cooled to 0-5° C. EDC (39.4 mg, 0.206 mmol) and DIPEA (35.4 mg, 0.274 mmol) were added. The resulting solution was allowed to warm up to rt over night. The reaction mixture was then partitioned between saturated aqueous NaHCO3 solution and EtOAc. The layers were separated, washed with saturated aqueous NaHCO3 solution, brine and EtOAc. The combined organic layers were dried over MgSO4.H2O and evaporated. The crude product was purified on a silica gel column by eluting with hexane/EtOAc 3/1->1.5/1 to give 67.7 mg of the title compound as a colorless resin.
Reaction SMILES: [N:1]([CH2:4][C@@H:5]1[C@H:9]2[O:10][C:11]([CH3:14])([CH3:13])[O:12][C@H:8]2[C@H:7]([N:15]2[C:19]3[N:20]=[CH:21][N:22]=[C:23]([N:24]=[N+]=[N-])[C:18]=3[CH:17]=[CH:16]2)[CH2:6]1)=[N+]=[N-].CP(C)C.O>C1COCC1>[NH2:1][CH2:4][C@@H:5]1[C@H:9]2[O:10][C:11]([CH3:14])([CH3:13])[O:12][C@H:8]2[C@H:7]([N:15]2[C:19]3[N:20]=[CH:21][N:22]=[C:23]([NH2:24])[C:18]=3[CH:17]=[CH:16]2)[CH2:6]1
Reactant: CC1(C)O[C@@H]2[C@@H](CN=[N+]=[N-])C[C@@H](n3ccc4c(N=[N+]=[N-])ncnc43)[C@@H]2O1
Agent: CP(C)C
Solvent: O
Solvent: C1CCOC1
Product: CC1(C)O[C@@H]2[C@@H](CN)C[C@@H](n3ccc4c(N)ncnc43)[C@@H]2O1
Reaction time: 8 h
Yield: 80.4 %

Procedure:
7-[(3aS,4R,6R,6aR)-6-(Azidomethyl)-2,2-dimethyl-hexahydrocyclopenta[d][1,3]dioxol-4-yl]-4-azido-7H-pyrrolo[2,3-d]pyrimidine (3.933 g, 11.1 mmol) was dissolved in THF (20 ml) and trimethylphosphane (1M in THF) (44.3 ml, 44.3 mmol) was added at r.t. under N2 and the reaction stirred overnight. Water (4 ml) was added and the reaction was left for 15 mins. The solvents were removed in vacuo to give the crude product. The product was purified by silica flash column chromatography using between 100% DCM to 20% 2M NH3 in MeOH:80% DCM as eluent to give the product as pale yellow foam (2.706 g, 81%): MS (ESI+) for C15H21N5O2 m/z 304.2 [M+H]+, 326.1 [M+Na]+; LCMS: Compound in solvent front; 1H NMR (500 MHz, CDCl3) δ 8.10 (s, 1H), 7.27 (d, J=3.63 Hz, 1H), 6.63 (d, J=3.63 Hz, 1H), 5.02 (dt, J=12.14, 6.23 Hz, 1H), 4.92-4.99 (m, 1H), 4.48-4.61 (m, 1H), 2.82-2.91 (m, 1H), 2.71-2.82 (m, 1H), 2.40 (dt, J=12.65, 6.52 Hz, 1H), 2.27 (m, 1H), 2.04 (q, J=12.14 Hz, 1H), 1.56 (s, 3H), 1.31 (s, 3H).
Reaction SMILES: [N+:1]([C:4]1[CH:14]=[CH:13][C:7]2[C:8]([NH:10][C:11](=[O:12])[C:5]=1[CH:6]=2)=[O:9])([O-:3])=[O:2].[CH:15](Br)([CH3:17])[CH3:16].C(=O)([O-])[O-].[K+].[K+].O>CN(C=O)C>[CH:15]([N:10]1[C:11](=[O:12])[C:13]2=[CH:14][C:4]([N+:1]([O-:3])=[O:2])=[CH:5][CH:6]=[C:7]2[C:8]1=[O:9])([CH3:17])[CH3:16]
Reactant: CC(C)Br
Reactant: O=C1NC(=O)c2cc1ccc2[N+](=O)[O-]
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: O
Product: CC(C)N1C(=O)c2ccc([N+](=O)[O-])cc2C1=O
Temperature: 60 °C
Yield: 70 %

Procedure:
4-Nitroisophthalimide (25.0 g, 130.0 mmol) was dissolved in DMF (250 mL). Isopropyl bromide (61.0 mL, 650 mmol) and potassium carbonate (36.0 g, 260 mmol) were added and the mixture was heated to 60° C. overnight. Water (1.0 L) was added, and the precipitate formed was collected by filtration, washed twice with water and dried overnight in a vacuum oven to afford 21.3 g (70%) of pure N-isopropyl-4-nitrophthalimide.
Reaction SMILES: Cl[CH2:2][CH2:3][CH2:4][CH2:5][S:6][C:7]1[N:12]2[CH:13]=[CH:14][N:15]=[C:11]2[CH:10]=[CH:9][CH:8]=1.[CH3:16][N:17]([CH:19]=[C:20]1[S:24][C:23](=[O:25])[NH:22][C:21]1=[O:26])[CH3:18].C1CCN2C(=NCCC2)CC1.O>CN(C)C=O>[CH3:18][N:17]([CH:19]=[C:20]1[S:24][C:23](=[O:25])[N:22]([CH2:2][CH2:3][CH2:4][CH2:5][S:6][C:7]2[N:12]3[CH:13]=[CH:14][N:15]=[C:11]3[CH:10]=[CH:9][CH:8]=2)[C:21]1=[O:26])[CH3:16]
Reactant: ClCCCCSc1cccc2nccn12
Reactant: CN(C)C=C1SC(=O)NC1=O
Solvent: O
Solvent: CN(C)C=O
Solvent: C1CCC2=NCCCN2CC1
Product: CN(C)C=C1SC(=O)N(CCCCSc2cccc3nccn23)C1=O
Temperature: 80 °C
Reaction time: 3 h

Procedure:
To a solution of 241 mg (1.0 mmol) of 5-(4-chlorobutylthio)imidazo[1,2-a]pyridine and 173 mg (1.0 mmol) of 5-(dimethylamino)methylene-thiazolidine-2,4-dione in 10 ml of N,N-dimethylformamide, 0.15 ml (1.0 mmol) of 1,8-diazabicyclo[5.4.0]-7-undecene was added, followed by stirring at 80°C. for 3 hours. After the reaction mixture was cooled, water was added; the mixture was extracted with ethyl acetate and dried, after which the solvent was distilled off. The residue was purified by column chromatography (eluent, n-hexane/ethyl acetate=1/4→ethyl acetate→chloroform/ethanol=10/1) to yield 310 mg (82.3%, yellow oily substance) of the desired product.
Reaction SMILES: [Br:1][C:2]1[CH:8]=[CH:7][C:5]([NH2:6])=[C:4]([N+:9]([O-])=O)[CH:3]=1.Cl[Sn]Cl>C(O)C>[Br:1][C:2]1[CH:8]=[CH:7][C:5]([NH2:6])=[C:4]([NH2:9])[CH:3]=1
Reactant: Nc1ccc(Br)cc1[N+](=O)[O-]
Agent: Cl[Sn]Cl
Solvent: CCO
Product: Nc1ccc(Br)cc1N
Yield: 94.2 %

Procedure:
4-Bromo-2-nitroaniline 600 mg (2.76 mmol) was dissolved in 25 ml absolute ethanol and 2.72 g (14 mmol) SnCl2 was added. The mixture was refluxed overnight. Ethanol was removed in vacuo and the mixture basified with 2N NaOH to pH 11. Ether extraction, drying the ether-layer over anhydrous Na2SO4 and concentration in vacuo afforded 486 mg (2.6 mmol, 94% yield) of the crude 4-bromo-o-phenylenediamine which was used for the next step without characterization.
Reaction SMILES: Cl.[O-:2][C:3]#[N:4].[Na+].[NH2:6][C:7]1[CH:36]=[CH:35][C:10]2[N:11]([CH:15]3[CH2:20][CH2:19][N:18]([CH2:21][CH2:22][CH2:23][C:24]([C:26]4[CH:31]=[C:30]([Br:32])[C:29]([NH2:33])=[C:28]([Br:34])[CH:27]=4)=[O:25])[CH2:17][CH2:16]3)[C:12](=[O:14])[NH:13][C:9]=2[CH:8]=1.[K+].[Br-].BrBr>C1COCC1>[NH2:4][C:3]([NH:6][C:7]1[CH:36]=[CH:35][C:10]2[N:11]([CH:15]3[CH2:16][CH2:17][N:18]([CH2:21][CH2:22][CH2:23][C:24]([C:26]4[CH:31]=[C:30]([Br:32])[C:29]([NH2:33])=[C:28]([Br:34])[CH:27]=4)=[O:25])[CH2:19][CH2:20]3)[C:12](=[O:14])[NH:13][C:9]=2[CH:8]=1)=[O:2]
Reactant: N#C[O-]
Reactant: Nc1ccc2c(c1)[nH]c(=O)n2C1CCN(CCCC(=O)c2cc(Br)c(N)c(Br)c2)CC1
Agent: BrBr
Agent: Cl
Agent: [Br-]
Solvent: C1CCOC1
Product: NC(=O)Nc1ccc2c(c1)[nH]c(=O)n2C1CCN(CCCC(=O)c2cc(Br)c(N)c(Br)c2)CC1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
1.5 ml of 1N hydrochloric acid, followed by 47 mg (0.723 mmol) of sodium cyanate were added to a solution of 200 mg (0.363 mmol) of 5-amino-1-{1-[4-(4-amino-3,5-dibromophenyl)-4-oxobutyl]-4-piperidinyl}-1,3-dihydro-2(2H)-benzimidazolone in 5 ml of THF at a reaction temperature of 0° C. The ice bath was removed and the mixture was stirred overnight at ambient temperature. The orange-coloured solution was carefully combined with 100 ml of conc. aqueous sodium hydrogen carbonate solution and overlaid with 50 ml of tert.butylmethyl ether. The precipitate formed was suction filtered and purified by column chromatography on silica gel (30–60 μm) using dichloromethane/methanol/cyclohexane/conc. ammonia 400/40/40/2.5 v/v/v/v as eluant. By working up the appropriate fractions 106 mg (44% of theoretical) of the desired compound were obtained in the form of colourless crystals (THF/diethylether 1/1 v/v)), Rf 0.12 (El B). IR (KBr): 3435.0, 3354.0 (NH, NH2); 1701.1, 1662.5 (C═O) MS: ESI: (M+H)+=593/595/597 (Br2); (M+Na)+615/617/619 (Br2)
Reaction SMILES: [C:1]([NH:5][C:6]([C:8]1[S:25][C:11]2[N:12]=[C:13]([S:23][CH3:24])[N:14]=[C:15]([C:16]3[CH:21]=[CH:20][CH:19]=[C:18]([NH2:22])[CH:17]=3)[C:10]=2[C:9]=1[NH2:26])=[O:7])([CH3:4])([CH3:3])[CH3:2].[C:27]1([CH3:37])[CH:32]=[CH:31][C:30]([S:33](Cl)(=[O:35])=[O:34])=[CH:29][CH:28]=1>N1C=CC=CC=1.C(Cl)Cl>[C:1]([NH:5][C:6]([C:8]1[S:25][C:11]2[N:12]=[C:13]([S:23][CH3:24])[N:14]=[C:15]([C:16]3[CH:21]=[CH:20][CH:19]=[C:18]([NH:22][S:33]([C:30]4[CH:31]=[CH:32][C:27]([CH3:37])=[CH:28][CH:29]=4)(=[O:35])=[O:34])[CH:17]=3)[C:10]=2[C:9]=1[NH2:26])=[O:7])([CH3:4])([CH3:2])[CH3:3]
Reactant: CSc1nc(-c2cccc(N)c2)c2c(N)c(C(=O)NC(C)(C)C)sc2n1
Reactant: Cc1ccc(S(=O)(=O)Cl)cc1
Solvent: c1ccncc1
Solvent: ClCCl
Product: CSc1nc(-c2cccc(NS(=O)(=O)c3ccc(C)cc3)c2)c2c(N)c(C(=O)NC(C)(C)C)sc2n1
Temperature: 25 °C
Reaction time: 2 h

Procedure:
tert-Butyl 5-amino-2-methylthio-4-(3-aminophenyl)-thieno[2,3-d]pyrimidine-6-carboxamide (example 9e, 100 mg) was dissolved in dry pyridine (5 ml). p-Toluenesulfonyl chloride (70 mg) was added and the mixture was stirred at room temperature for 2 h. The reaction mixture was diluted with CH2Cl2 and washed with 0.1M aq. HCl. The organic layer was dried (MgSO4) and concentrated under reduced pressure. The title compound was purified by chromatography on silica gel with hept/EtOAc=3/2 (v/v) as eluent.
Reaction SMILES: Cl[C:2]1[C:11]2[C:6](=[C:7]([CH3:12])[CH:8]=[CH:9][CH:10]=2)[N:5]=[C:4]([CH3:13])[CH:3]=1.[Cl:14][C:15]1[CH:16]=[C:17]([CH:20]=[CH:21][C:22]=1[Cl:23])[CH2:18][NH2:19]>>[Cl:14][C:15]1[CH:16]=[C:17]([CH:20]=[CH:21][C:22]=1[Cl:23])[CH2:18][NH:19][C:2]1[C:11]2[C:6](=[C:7]([CH3:12])[CH:8]=[CH:9][CH:10]=2)[N:5]=[C:4]([CH3:13])[CH:3]=1
Reactant: Cc1cc(Cl)c2cccc(C)c2n1
Reactant: NCc1ccc(Cl)c(Cl)c1
Product: Cc1cc(NCc2ccc(Cl)c(Cl)c2)c2cccc(C)c2n1

Procedure:
Preparation was made using a similar procedure as described in example 1, method 1.3. Starting materials were 4-chloro-2-methyl-8-methylquinoline and 3,4-dichlorobenzylamine.
Reaction SMILES: [C:1]([C:3]1[CH:4]=[CH:5][C:6]([C:9]([OH:11])=O)=[N:7][CH:8]=1)#[N:2].C(N(C(C)C)CC)(C)C.C1CN([P+](ON2N=NC3C=CC=CC2=3)(N2CCCC2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F.[NH2:54][C:55]1[CH:56]=[C:57]([C@@:66]23[N:75]=[C:74]([NH:76]C(=O)OC(C)(C)C)[S:73][CH2:72][C@@H:71]2[CH2:70][CH2:69][O:68][CH2:67]3)[C:58]2[O:62][C:61]([F:64])([F:63])[O:60][C:59]=2[CH:65]=1.C(O)(C(F)(F)F)=O.C(=O)(O)[O-].[Na+]>ClCCl.O>[NH2:76][C:74]1[S:73][CH2:72][C@H:71]2[C@:66]([C:57]3[C:58]4[O:62][C:61]([F:64])([F:63])[O:60][C:59]=4[CH:65]=[C:55]([NH:54][C:9]([C:6]4[CH:5]=[CH:4][C:3]([C:1]#[N:2])=[CH:8][N:7]=4)=[O:11])[CH:56]=3)([CH2:67][O:68][CH2:69][CH2:70]2)[N:75]=1
Reactant: CC(C)(C)OC(=O)NC1=N[C@@]2(c3cc(N)cc4c3OC(F)(F)O4)COCC[C@H]2CS1
Reactant: N#Cc1ccc(C(=O)O)nc1
Agent: F[P-](F)(F)(F)(F)F
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CCN(C(C)C)C(C)C
Solvent: O
Solvent: ClCCl
Product: N#Cc1ccc(C(=O)Nc2cc3c(c([C@]45COCC[C@H]4CSC(N)=N5)c2)OC(F)(F)O3)nc1
Temperature: 25 °C
Reaction time: 4 h

Procedure:
5-Cyanopyridine-2-carboxylic acid (4.0 mg), diisopropylethylamine (11.5 μl) and PyBOP (17.6 mg) were added to a solution of tert-butyl (±)-[(4aR*,8aS*)-8a-(6-amino-2,2-difluorobenzo[1,3]dioxol-4-yl)-4,4a,5,6,8,8a-hexahydro-7-oxa-3-thia-1-azanaphthalen-2-yl]carbamate (10 mg) in dichloromethane (2.0 ml) in an ice bath. The mixture was heated to room temperature and stirred for four hours. The solvent was evaporated under reduced pressure and the residue was purified by NH-pTLC to obtain an intermediate. The resulting intermediate was dissolved in dichloromethane (3.0 ml) and TFA (1.0 ml) was added. After stirring at room temperature for four hours, the reaction solution was diluted with water and neutralized with a sodium bicarbonate solution. The aqueous layer was extracted with dichloromethane, and the organic layer was dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure and the residue was purified by NH-pTLC to obtain the title compound.
Reaction SMILES: C([CH2:8][C:9]([CH3:20])([OH:19])[CH:10]([NH2:18])[CH2:11][C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1)(OC(C)(C)C)=O.[ClH:21]>C(OCC)(=O)C>[ClH:21].[NH2:18][CH:10]([CH2:11][C:12]1[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=1)[C:9]([CH3:8])([OH:19])[CH3:20]
Reactant: CC(C)(C)OC(=O)CC(C)(O)C(N)Cc1ccccc1
Agent: Cl
Solvent: CCOC(C)=O
Product: CC(C)(O)C(N)Cc1ccccc1
Temperature: 25 °C
Reaction time: 1 h

Procedure:
A solution of Boc-3-amino-2-methyl-4-phenylbutan-2-ol (0.34 g, 1.2 mmol) in 100 mL ethyl acetate was saturated with HCl gas and stirred at ambient temperature for 1 hour. The reaction was evaporated in vacuo to give 3-amino-2-methyl-4-phenylbutan-2-ol hydrochloride as a white solid: 1H NMR (400 MHz, CDCl3) δ 8.05 (bs, 2H), 7.33 (m, 5H), 3.34 (m, 1H), 3.02 (m, 2H), 1.37 (s, 3H), 1.33 (s, 3H).
Reaction SMILES: N[C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[CH:8]=[C:7]([S:12]([OH:15])(=[O:14])=[O:13])[CH:6]=[CH:5]2.N([O-])=O.[Na+].[ClH:20]>O.[Cu]Cl>[Cl:20][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[CH:8]=[C:7]([S:12]([OH:15])(=[O:14])=[O:13])[CH:6]=[CH:5]2
Reactant: Nc1ccc2cc(S(=O)(=O)O)ccc2c1
Reactant: Cl
Agent: Cl[Cu]
Agent: O=N[O-]
Agent: [Na+]
Solvent: O
Product: O=S(=O)(O)c1ccc2cc(Cl)ccc2c1
Reaction time: 8 h

Procedure:
6-Amino-2-napthalenesulfonic acid (88.0 g, 0.4 mol) was suspended in 5 N HCl (200 mL) and water (150 mL) and cooled to 3° C. A solution of sodium nitrite (27.0 g, 0.4 mol) in water (50 mL) was added dropwise over two hours. After one additional hour, the mixture was poured in several portions into a stirred suspension of copper(I) chloride (39.6 g, 60.6 mmol) in 5 N HCl (200 mL). Considerable foaming occurred during this addition. After standing overnight at room temperature, the mixture was concentrated on a rotary evaporator to a brown solid that was then dried in a vacuum oven overnight at 100° C. to provide the acid (111.9 g).
Reaction SMILES: C([O-])([O-])=O.[K+].[K+].I[CH3:8].[Cl:9][C:10]1[C:19]([I:20])=[CH:18][C:13]2[NH:14][C:15](=[S:17])[NH:16][C:12]=2[CH:11]=1>CC(C)=O>[Cl:9][C:10]1[C:19]([I:20])=[CH:18][C:13]2[N:14]=[C:15]([S:17][CH3:8])[NH:16][C:12]=2[CH:11]=1
Reactant: CI
Reactant: S=c1[nH]c2cc(Cl)c(I)cc2[nH]1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC(C)=O
Product: CSc1nc2cc(I)c(Cl)cc2[nH]1
Temperature: 25 °C
Reaction time: 1 h

Procedure:
K2CO3 (0.22 g, 1.61 mmol), followed by iodomethane (0.1 mL, 1.61 mmol), was added to a solution of 5-chloro-6-iodo-1,3-dihydro-2H-benzimidazole-2-thione (1 g, 3.22 mmol) in acetone (20 mL) at 0° C. The reaction was stirred at rt for 1 h. Additional K2CO3 (1.61 mmol) and iodomethane (1.61 mmol) were added, and stirring continued at rt overnight. Volatiles were removed and the residue was partitioned between EtOAc and water. Concentration afforded the desired product as a white foam, which was used in the next step without further purification.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]2[C:17]3[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=3)[N:11](S(C3C=CC=CC=3)(=O)=O)[CH:10]=2)=[CH:5][CH:4]=1.C(=O)([O-])[O-].[K+].[K+]>CO>[CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]([C:9]2[C:17]3[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=3)[NH:11][CH:10]=2)=[CH:7][CH:8]=1
Reactant: COc1ccc(-c2cn(S(=O)(=O)c3ccccc3)c3ccccc23)cc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CO
Product: COc1ccc(-c2c[nH]c3ccccc23)cc1
Temperature: 25 °C
Yield: 98.6 %

Procedure:
3-(4-methoxyphenyl)-1-(phenylsulfonyl)-1H-indole (200 mg, 0.55 mmol) and 15 eq potassium carbonate were dissolved in 40 ml MeOH under nitrogen. The mixture was heated at reflux for 16 h, cooled to rt and then concentrated to dryness. DCM and brine were added and the mixture was acidified (pH 2-4) with 2 M HCl. The aqueous layer was extracted with DCM and the combined organic layers were concentrated. The crude product was purified on silica (EtOAc/n-Heptane, 1:1). 121.1 mg 3-(4-methoxyphenyl)-1H-indole was obtained as a white solid.
Reaction SMILES: C(Cl)(=O)C.[NH:5]1[CH2:10][CH:9]=[C:8]([C:11]2[CH:16]=[CH:15][C:14]([NH:17][C:18]([N:20]3[CH2:28][C:27]4[CH:26]=[CH:25][N:24]=[CH:23][C:22]=4[CH2:21]3)=[O:19])=[CH:13][CH:12]=2)[CH2:7][CH2:6]1.NC1C=C2C(=CC=1)CN(C(N[C:42]1[CH:47]=[CH:46][C:45]([C:48](=[O:53])NCCC)=[CH:44][CH:43]=1)=O)C2>>[C:48]([N:5]1[CH2:6][CH:7]=[C:8]([C:11]2[CH:16]=[CH:15][C:14]([NH:17][C:18]([N:20]3[CH2:28][C:27]4[CH:26]=[CH:25][N:24]=[CH:23][C:22]=4[CH2:21]3)=[O:19])=[CH:13][CH:12]=2)[CH2:9][CH2:10]1)(=[O:53])[C:45]1[CH:46]=[CH:47][CH:42]=[CH:43][CH:44]=1
Reactant: O=C(Nc1ccc(C2=CCNCC2)cc1)N1Cc2ccncc2C1
Reactant: CCCNC(=O)c1ccc(NC(=O)N2Cc3ccc(N)cc3C2)cc1
Solvent: CC(=O)Cl
Product: O=C(Nc1ccc(C2=CCN(C(=O)c3ccccc3)CC2)cc1)N1Cc2ccncc2C1

Procedure:
The title compound was prepared as described in Example 278, substituting benzoyl chloride for acetyl chloride and N-(4-(1,2,3,6-tetrahydropyridin-4-yl)phenyl)-1H-pyrrolo[3,4-c]pyridine-2(3H)-carboxamide for 5-amino-N-(4-(propylcarbamoyl)phenyl)isoindoline-2-carboxamide. 1H NMR (400 MHz, DMSO-d6) δ ppm 8.61 (s, 1H), 8.50 (d, J=5.0 Hz, 1H), 8.46 (s, 1H), 7.55-7.58 (m, 2H), 7.42-7.49 (m, 6H), 7.35-7.41 (m, 2H), 5.98-6.21 (m, 1H), 4.79-4.82 (m, 4H), 3.95-4.39 (m, 2H), 3.79-3.93 (m, 1H), 3.51-3.61 (m, 1H), 2.46-2.60 (m, 2H); MS (ESI(+)) m/e 425 (M+H)+.
Reaction SMILES: [Pb:1](Cl)[Cl:2].O.[S:5]([O-:9])([O-:8])(=[O:7])=[O:6].[Ca+2:10]>[Cl-].[Na+].O>[S:5]([O-:9])([O-:8])(=[O:7])=[O:6].[Pb+2:1].[Cl-:2].[Ca+2:10].[Cl-:2]
Reactant: Cl[Pb]Cl
Agent: O=S(=O)([O-])[O-]
Agent: [Ca+2]
Agent: [Cl-]
Solvent: O
Product: [Pb+2]

Procedure:
Australian Pat. No. 28,957, (1971) describes a method of precipitating lead chloride from brine solution by cooling followed by reacting said lead chloride with water and calcium sulphate to produce a lead sulphate precipitate and calcium chloride solution. Although low chloride levels in the lead sulphate were obtainable with rigorous washing, the product is again suitable to lead smelters in limited quantities and must be treated on a sinter machine to remove sulphur before the blast. Capital and operating costs are projected to be high for the process since the brine solution must be heated for high lead solubility and then cooled for lead chloride precipitation.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([CH2:9][C:10](Cl)=[O:11])[CH:5]=[CH:6][C:7]=1[Cl:8].[C:13]1([NH:19][CH2:20][CH2:21][C:22]([O:24][CH2:25][CH3:26])=[O:23])[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1>>[Cl:1][C:2]1[CH:3]=[C:4]([CH2:9][C:10]([N:19]([CH2:20][CH2:21][C:22]([O:24][CH2:25][CH3:26])=[O:23])[C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)=[O:11])[CH:5]=[CH:6][C:7]=1[Cl:8]
Reactant: O=C(Cl)Cc1ccc(Cl)c(Cl)c1
Reactant: CCOC(=O)CCNc1ccccc1
Product: CCOC(=O)CCN(C(=O)Cc1ccc(Cl)c(Cl)c1)c1ccccc1

Procedure:
By a procedure similar to that of example 1.115.1, starting from 3,4-dichlorophenylacetyl chloride and ethyl N-phenyl-3-aminopropionate, ethyl 3-[2-(3,4-dichlorophenyl)-N-phenyl-acetamido]propanoate was obtained as yellowish oil.
Reaction SMILES: [Cl-].[Ca+2].[Cl-].C(Br)(=O)C.[CH3:8][N:9]([C:13]([NH2:15])=[NH:14])[CH2:10][CH2:11][OH:12].[C:16](O)(=[O:38])[CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][CH2:34][CH2:35][CH2:36][CH3:37]>C(Cl)Cl>[C:16]([O:12][CH2:11][CH2:10][N:9]([CH3:8])[C:13]([NH2:15])=[NH:14])(=[O:38])[CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][CH2:34][CH2:35][CH2:36][CH3:37]
Reactant: CN(CCO)C(=N)N
Reactant: CCCCCCCCCCCCCCCCCCCCCC(=O)O
Agent: CC(=O)Br
Agent: [Ca+2]
Agent: [Cl-]
Solvent: ClCCl
Product: CCCCCCCCCCCCCCCCCCCCCC(=O)OCCN(C)C(=N)N
Temperature: 0 °C
Reaction time: 0.25 h

Procedure:
In a dry 3-necked round bottomed flask, containing a magnetic stirrer, equipped with a dropping funnel, a reflux condenser protected from moisture by a calcium chloride filled drying tube and a rubber septum. The dropping funnel is filled with 12.73 mL (150 mmol) of acetyl bromide and 35 mL of dry DCM. The flask is charged with 35.14 g (300 mmol) of Creatinol and 150 mL of dry DCM, and cooled with an ice-water bath to about 0° C., under a nitrogen atmosphere. The acetyl bromide solution is then added slowly with stirring, over a period of 10 minutes, to the Creatinol solution. The solution is stirred for another 15 minutes, after which 23.84 g (70 mmol) of Docosanoic acid is added in one portion and the reaction is slowly heated to about 65° C. for about 12 hours. Then the solution is allowed to cool to room temperature, after which the solvent is removed under reduced pressure to yield the crude ester. The crude ester is then purified by flash chromatography (ethyl acetate/hexanes; 1/3) to yield pure 2-(1-methylguanidino)ethyl docosanoate.
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)/[C:7](=[CH:11]\[C:12]1[CH:17]=[CH:16][N:15]=[CH:14][CH:13]=1)/[C:6]([CH3:18])=[C:5]2[CH2:19][CH2:20][O:21][NH2:22].[CH3:23][O:24][CH2:25][CH:26]=O>>[F:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)/[C:7](=[CH:11]\[C:12]1[CH:13]=[CH:14][N:15]=[CH:16][CH:17]=1)/[C:6]([CH3:18])=[C:5]2[CH2:19][CH2:20][O:21][N:22]=[CH:26][CH2:25][O:24][CH3:23]
Reactant: COCC=O
Reactant: CC1=C(CCON)c2cc(F)ccc2/C1=C\c1ccncc1
Product: COCC=NOCCC1=C(C)/C(=C/c2ccncc2)c2ccc(F)cc21

Procedure:
The title compound is prepared by reaction of O-2-[Z-5-fluoro-2-methyl-1-(4-pyridyl)methylene-1H-inden-3-yl]ethyl hydroxylamine with methoxyacetaldehyde by the method of Example 1.