Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[N:11]([CH2:12][CH2:13][CH2:14][C:15]3([CH3:20])[O:19][CH2:18][CH2:17][O:16]3)[C:10](=[O:21])[CH2:9][N:8]=[C:7]([C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=3)[C:6]=2[CH:28]=1.CN(C)C=O.[H-].[Na+]>O>[CH3:20][C:15]1([CH2:14][CH2:13][CH2:12][NH:11][C:10]([C:9]2[NH:8][C:7]([C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=3)=[C:6]3[C:5]=2[CH:4]=[CH:3][C:2]([Cl:1])=[CH:28]3)=[O:21])[O:19][CH2:18][CH2:17][O:16]1
Reactant: CC1(CCCN2C(=O)CN=C(c3ccccc3)c3cc(Cl)ccc32)OCCO1
Agent: [H-]
Agent: [Na+]
Solvent: O
Solvent: CN(C)C=O
Product: CC1(CCCNC(=O)c2[nH]c(-c3ccccc3)c3cc(Cl)ccc23)OCCO1
Temperature: 60 °C
Reaction time: 1 h

Procedure:
A solution of 40.0 g. of 7-chloro-1,3-dihydro-1-[3-(2-methyl-1,3-dioxolan-2-yl)propyl]-5-phenyl-2H-1,4-benzodiazepin-2-one in 500 ml. of dimethylformamide is treated under an atomsphere of argon at room temperature with 0.115 mol. of sodium hydride (5.1 g. of a 55% dispersion in mineral oil). The mixture is warmed to 60° C. over a period of about 30 minutes, then stirred at this temperature for 1 hour and thereafter at 70° C. for an additional hour. After cooling, 10 ml. of water are added dropwise and the mixture is poured on to 4 liters of ice-water. After the addition of 150 g. of sodium chloride, the separated product is removed by filtration, washed with water and dissolved in methylene chloride. The organic solution is dried over sodium sulfate and concentrated to dryness. The residue is chromatographed on 1000 g. of silica gel using methylene chloride/ethyl acetate (4:1) for the elution. The homogeneous fractions are combined and evaporated. The residual oil crystallizes upon trituration with hexane, and there is obtained 5-chloro-3-phenylisoindole-1-carboxylic acid [3-(2-methyl-1,3-dioxolan-2-yl)propyl]amide in the form of yellowish crystals having a melting point of 157°-159° C. Recrystallization from ethanol does not increase the melting point.
Reaction SMILES: C(Cl)(=O)C.C([NH:8][C:9]1[CH:14]=[C:13]([C:15]2[CH:20]=[CH:19][C:18]([I:21])=[C:17]([F:22])[C:16]=2[F:23])[N:12]=[C:11]([C:24]([O:26][CH3:27])=[O:25])[C:10]=1[Cl:28])(=O)C>CO>[NH2:8][C:9]1[CH:14]=[C:13]([C:15]2[CH:20]=[CH:19][C:18]([I:21])=[C:17]([F:22])[C:16]=2[F:23])[N:12]=[C:11]([C:24]([O:26][CH3:27])=[O:25])[C:10]=1[Cl:28]
Reactant: COC(=O)c1nc(-c2ccc(I)c(F)c2F)cc(NC(C)=O)c1Cl
Solvent: CO
Solvent: CC(=O)Cl
Product: COC(=O)c1nc(-c2ccc(I)c(F)c2F)cc(N)c1Cl
Temperature: 23 °C
Yield: 94.2 %

Procedure:
Acetyl chloride (1.3 mL, 18 mmol, 10 equiv) was slowly added to methanol (12 mL) and stirred at 23° C. for 30 m. Methyl 4-acetamido-3-chloro-6-(2,3-difluoro-4-iodophenyl)picolinate (830 mg, 1.8 mmol, 1.0 equiv) was added and the heterogeneous white mixture was stirred at 23° C. for 18 h. The reaction mixture was concentrated by rotary evaporation. The residue was diluted with saturated sodium bicarbonate (200 mL) and extracted with dichloromethane (3×75 mL). The organic layer was dried (magnesium sulfate), gravity filtered, and concentrated by rotary evaporation to afford the title compound as a white powder (720 mg, 95%).
Reaction SMILES: [Cl-].[OH:2][NH3+:3].C([O-])(=O)C.[Na+].[CH:9](=O)[CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH3:16]>O.C(O)C>[CH:9](=[N:3][OH:2])[CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH3:16]
Reactant: [NH3+]O
Reactant: CCCCCCCC=O
Agent: CC(=O)[O-]
Agent: [Cl-]
Agent: [Na+]
Solvent: O
Solvent: CCO
Product: CCCCCCCC=NO
Yield: 270.8 %

Procedure:
To hydroxylammonium chloride (0.39 g; 5.57 mmol) and sodium acetate (0.54 g; 6.57 mmol) dissolved in 5 ml of water is added 1-(6-Benzoyl-9-ethyl-9.H.-carbazol-3-yl)-octan-1-one (2.14 g; 5.03 mol) in 15 ml of ethanol. After refluxing for 7 h, H2O is added to the reaction mixture, the resulting white solid is filtered off, washed with water and dissolved in tetrahydrofurane (THF). After drying this THF solution over anhydrous MgSO4, condensation under reduced pressure affords 2.16 g of a pale yellow solid (97%).
Reaction SMILES: [NH2:1][CH2:2][CH:3]([C:5]1[S:6][CH:7]=[CH:8][CH:9]=1)[OH:4].CC1(C)[NH:16][C:15](=[O:17])[C:14]2[CH:18]=[C:19]([O:22][CH2:23][CH2:24]Br)[CH:20]=[CH:21][C:13]=2[O:12]1>C(N(CC)CC)C>[C:15]([C:14]1[CH:18]=[C:19]([CH:20]=[CH:21][C:13]=1[OH:12])[O:22][CH2:23][CH2:24][NH:1][CH2:2][CH:3]([C:5]1[S:6][CH:7]=[CH:8][CH:9]=1)[OH:4])(=[O:17])[NH2:16]
Reactant: NCC(O)c1cccs1
Reactant: CC1(C)NC(=O)c2cc(OCCBr)ccc2O1
Solvent: CCN(CC)CC
Product: NC(=O)c1cc(OCCNCC(O)c2cccs2)ccc1O

Procedure:
A mixture of 2.7 g of α-(aminomethyl)-2-thiophenmethanol and 3.6 g of 2,3-dihydro-2,2-dimethyl-6-(2-bromoethoxy)-4H-1,3-benzoxazin-4-one is stirred together with 2 ml of triethylamine for 1 hour in a bath at 100°-110°. The reaction mixture is partitioned between 100 ml of ethyl acetate and 10 ml of 2N aqueous potassium bicarbonate solution and the organic phase is separated off, dried over magnesium sulfate and evaporated, yielding crude α-[N-[2-(3-carbamoyl-4-hydroxy-phenoxy)-ethyl]-amino-methyl]-2-thiophen-methanol in the form of a crystalline mass which after recrystallisation from a little isopropanol melts at 158°-161°; repeated recrystallisation raises the melting point to 171°-172°.
Reaction SMILES: [C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][NH:11][CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH3:14][C:15]1[C:19]([CH3:20])=[C:18]([NH:21][C:22](=O)[O:23]CC(Cl)(Cl)Cl)[O:17][N:16]=1.CS(C)=O>O>[CH3:14][C:15]1[C:19]([CH3:20])=[C:18]([NH:21][C:22]([N:11]2[CH2:12][CH2:13][N:8]([C:6]([O:5][C:1]([CH3:4])([CH3:2])[CH3:3])=[O:7])[CH2:9][CH2:10]2)=[O:23])[O:17][N:16]=1
Reactant: Cc1noc(NC(=O)OCC(Cl)(Cl)Cl)c1C
Reactant: CC(C)(C)OC(=O)N1CCNCC1
Solvent: CS(C)=O
Solvent: O
Product: Cc1noc(NC(=O)N2CCN(C(=O)OC(C)(C)C)CC2)c1C
Yield: 41.4 %

Procedure:
A solution of 1-(tert-butoxycarbonyl)piperazine (5.00 g, 26.8 mmol), 2,2,2-trichloroethyl (3,4-dimethylisoxazol-5-yl)carbamate (3.85 g, 13.4 mmol), disopropylethylamine (2.33 ml, 13.4 mmol) and dimethylsulfoxide (50 ml) was stirred at 70° C. for 2 hours, the reaction mixture was poured into water, and the mixture was extracted with ethyl acetate. The extract was washed with water and dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure. The residue was recrystallized from a mixed solvent of ethyl acetate and hexane to obtain the desired product (1.80 g, 41.4%) as a solid.
Reaction SMILES: N1C=CC=CC=1.[CH2:7]([O:14][N:15]1[C:21](=[O:22])[N:20]2[CH2:23][C@H:16]1[CH2:17][CH2:18][C@H:19]2[C:24]([NH:26][NH:27][C:28]([N:30]1[CH2:35][CH2:34][N:33]([C:36]([O:38][C:39]([CH3:42])([CH3:41])[CH3:40])=[O:37])[CH2:32][CH2:31]1)=[O:29])=O)[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1.O(S(C(F)(F)F)(=O)=O)S(C(F)(F)F)(=O)=O.C([O-])(O)=O.[Na+]>C(Cl)Cl>[CH2:7]([O:14][N:15]1[C:21](=[O:22])[N:20]2[CH2:23][C@H:16]1[CH2:17][CH2:18][C@H:19]2[C:24]1[O:29][C:28]([N:30]2[CH2:35][CH2:34][N:33]([C:36]([O:38][C:39]([CH3:41])([CH3:42])[CH3:40])=[O:37])[CH2:32][CH2:31]2)=[N:27][N:26]=1)[C:8]1[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=1
Reactant: CC(C)(C)OC(=O)N1CCN(C(=O)NNC(=O)[C@@H]2CC[C@@H]3CN2C(=O)N3OCc2ccccc2)CC1
Agent: O=C([O-])O
Agent: O=S(=O)(OS(=O)(=O)C(F)(F)F)C(F)(F)F
Agent: [Na+]
Solvent: ClCCl
Solvent: c1ccncc1
Product: CC(C)(C)OC(=O)N1CCN(c2nnc([C@@H]3CC[C@@H]4CN3C(=O)N4OCc3ccccc3)o2)CC1
Temperature: 25 °C
Reaction time: 3 h
Yield: 82.9 %

Procedure:
Pyridine (2.8 mL, 36.0 mmol was added to a solution of tert-butyl 4-(2-((2S,5R)-6-(benzyloxy)-7-oxo-1,6-diaza-bicyclo[3.2.1]octane-2-carbonyl)hydrazine-carbonyl)piperazine-1-carboxylate (903 mg, 1.8 mmol) in DCM (200 mL). (CF3SO2)2O (2.8 ml, 9.0 mmol) was then added slowly at −10° C. The reaction mixture was stirred at rt for 3 hrs. Saturated NaHCO3 was added at −10° C. very slowly. The combined organic layer was separated and the aqueous layer was exacted with EtOAc (3×). The combined organic layer was dried over Na2SO4, and concentrated. The crude product was purified by silica gel column chromatography (2:1 EtOAc/hexanes) to give tert-butyl 4-(5-((2S,5R)-6-(benzyloxy)-7-oxo-1,6-diaza-bicyclo[3.2.1]octan-2-yl)-1,3,4-oxadiazol-2-yl)piperazine-1-carboxylate (723 mg, 83%) as a slight yellow solid. ESI-MS (EI+, m/z): 485.2 [M+H]+.
Reaction SMILES: [Cl:1][C:2]1[N:7]=[C:6]([O:8][C:9]([CH3:14])([CH3:13])[C:10]([OH:12])=O)[CH:5]=[CH:4][CH:3]=1.[NH2:15][C:16]1[C:21]([NH2:22])=[CH:20][CH:19]=[CH:18][N:17]=1.CCN=C=NCCCN(C)C>CN(C=O)C>[NH2:22][C:21]1[C:16]([NH:15][C:10](=[O:12])[C:9]([O:8][C:6]2[CH:5]=[CH:4][CH:3]=[C:2]([Cl:1])[N:7]=2)([CH3:14])[CH3:13])=[N:17][CH:18]=[CH:19][CH:20]=1
Reactant: CC(C)(Oc1cccc(Cl)n1)C(=O)O
Reactant: Nc1cccnc1N
Agent: CCN=C=NCCCN(C)C
Solvent: CN(C)C=O
Product: CC(C)(Oc1cccc(Cl)n1)C(=O)Nc1ncccc1N
Temperature: 0 °C
Reaction time: 4 h
Yield: 73.4 %

Procedure:
2-(6-Chloro-pyridin-2-yloxy)-2-methyl-propionic acid (0.53 g, 2.4 mmol) and 2,3-diaminopyridine (0.268 g, 2.4 mmol) were dissolved in DMF (5 ml) cooled to 0° C. and added EDCI (0.62 g, 3.2 mmol) and stirred for 4 h. The reaction mixture was extracted in EtOAc (30 ml) and washed with brine (2×10 ml) dried over Na2SO4 and concentrated under reduced pressure to obtain crude product. The product was purified on silica gel to yield N-(3-Amino-pyridin-2-yl)-2-(6-chloro-pyridin-2-yloxy)-2-methyl-propionamide (0.54 g, 72%). 1H NMR (400 MHz, CDCl3): 4.84 (brs, 2H), 6.67 (dd, J=4.8 and 7.6 Hz, 1H), 6.78 (d, J=8.4 Hz, 1H), 7.02 (d, J=8. Hz, 1H), 7.40 (d, J=8. Hz, 1H), 7.61 (d, J=8 Hz, 1H), 7.996 (dd, J=4.8 Hz and 7.6 Hz, 1H). MS (EI) m/z: 307 (M+1).
Reaction SMILES: [C:1]1(C)[CH:6]=[CH:5][C:4]([S:7]([OH:10])(=[O:9])=[O:8])=[CH:3][CH:2]=1.[NH2:12][C:13]1[S:14][CH:15]=[C:16](/[C:18](=[N:46]/[OH:47])/[C:19]([NH:21][CH:22]2[C:44](=[O:45])[N:24]3[C:25]([C:32]([O:34][CH:35]([O:37][C:38](=[O:43])[C:39]([CH3:42])([CH3:41])[CH3:40])[CH3:36])=[O:33])=[C:26]([CH2:29][O:30][CH3:31])[CH2:27][S:28][C@H:23]23)=[O:20])[N:17]=1.C(OC(C)C)(C)C>CC(C)=O>[C:3]1([CH3:13])[C:4]([S:7]([OH:10])(=[O:8])=[O:9])=[CH:5][CH:6]=[CH:1][CH:2]=1.[NH2:12][C:13]1[S:14][CH:15]=[C:16](/[C:18](=[N:46]/[OH:47])/[C:19]([NH:21][CH:22]2[C:44](=[O:45])[N:24]3[C:25]([C:32]([O:34][CH:35]([O:37][C:38](=[O:43])[C:39]([CH3:41])([CH3:42])[CH3:40])[CH3:36])=[O:33])=[C:26]([CH2:29][O:30][CH3:31])[CH2:27][S:28][C@H:23]23)=[O:20])[N:17]=1
Reactant: Cc1ccc(S(=O)(=O)O)cc1
Agent: COCC1=C(C(=O)OC(C)OC(=O)C(C)(C)C)N2C(=O)C(NC(=O)/C(=N\O)c3csc(N)n3)[C@H]2SC1
Solvent: CC(C)OC(C)C
Solvent: CC(C)=O
Product: Cc1ccccc1S(=O)(=O)O

Procedure:
A solution of 1.8 g (15 mmol) of p-toluenesulfonic acid in 5 ml of acetone was added dropwise to a solution of 5 g (9.3 mmol) of α-(2,2-dimethylpropanoyloxy)ethyl 7-[2-(2-aminothiazol-4-yl)-2-(Z)-hydroxyimino-acetamido]-3-methoxymethyl-3-cephem-4-carboxylate in 35 ml of acetone. After stirring briefly, a thick precipitate formed. After stirring for 15 minutes, a total of 185 ml of diisopropyl ether were slowly added dropwise to complete crystallization and the mixture was stirred for a short time. The precipitate was then filtered off with suction, washed with a little diisopropyl ether and dried in vacuo over calcium chloride/paraffin. 5.9 g of crystalline title compound were obtained, which consisted of an approximately 1:1 mixture of the two diastereomers according to HPLC and was identical in its physical and chemical properties with the product from working example 2.
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]([C:8]2[C:9]([N:17]3[CH2:22][CH2:21][NH:20][CH2:19][CH2:18]3)=[C:10]3[CH:16]=[CH:15][NH:14][C:11]3=[N:12][CH:13]=2)[CH:5]=[CH:6][CH:7]=1.[C:23]([O:27][C:28]([NH:30][C@H:31]([CH2:35][C:36]1[CH:41]=[CH:40][C:39]([Cl:42])=[CH:38][CH:37]=1)[C:32](O)=[O:33])=[O:29])([CH3:26])([CH3:25])[CH3:24].C1C=CC2N(O)N=NC=2C=1.O.CCN=C=NCCCN(C)C.CCN(C(C)C)C(C)C>C(Cl)Cl>[Cl:42][C:39]1[CH:40]=[CH:41][C:36]([CH2:35][C@@H:31]([NH:30][C:28](=[O:29])[O:27][C:23]([CH3:25])([CH3:24])[CH3:26])[C:32]([N:20]2[CH2:19][CH2:18][N:17]([C:9]3[C:8]([C:4]4[CH:5]=[CH:6][CH:7]=[C:2]([F:1])[CH:3]=4)=[CH:13][N:12]=[C:11]4[NH:14][CH:15]=[CH:16][C:10]=34)[CH2:22][CH2:21]2)=[O:33])=[CH:37][CH:38]=1
Reactant: Fc1cccc(-c2cnc3[nH]ccc3c2N2CCNCC2)c1
Reactant: CC(C)(C)OC(=O)N[C@H](Cc1ccc(Cl)cc1)C(=O)O
Agent: CCN=C=NCCCN(C)C
Agent: On1nnc2ccccc21
Solvent: ClCCl
Solvent: CCN(C(C)C)C(C)C
Solvent: O
Product: CC(C)(C)OC(=O)N[C@H](Cc1ccc(Cl)cc1)C(=O)N1CCN(c2c(-c3cccc(F)c3)cnc3[nH]ccc23)CC1
Temperature: 25 °C
Reaction time: 2 h
Yield: 46.3 %

Procedure:
5-(3-Fluorophenyl)-4-(piperazin-1-yl)-1H-pyrrolo[2,3-b]pyri dine (0.062 g, 0.168 mmol) and (R)-2-(tert-butoxycarbonylamino)-3-(4-chlorophenyl)propanoic acid (0.0604 g, 0.201 mmol) were placed in DCM (3 mL) at room temperature. HOBT-H2O (0.0360 g, 0.235 mmol), EDCI (0.0418 g, 0.218 mmol), and DIEA (d 0.742; 0.146 mL, 0.840 mmol) were then added. The reaction was stirred at room temperature for 2 hours. The reaction was then quenched with saturated Na2CO3 and extracted with DCM. The organic fractions were dried, filtered, and concentrated to give a crude oil. The oil was purified by column chromatography (500:5 D CM: MeOH) to give (R)-tert-butyl 3-(4-chlorophenyl)-1-(4-(5-(3-fluorophenyl)-1H-pyrrolo[2,3-b]pyridin-4-yl)piperazin-1-yl)-1-oxopropan-2-ylcarbamate (0.045 g, 46.3% yield).
Reaction SMILES: [CH:1]([OH:3])=O.C(OC(=O)C)(=O)C.[F:11][C:12]([F:26])([F:25])[C:13]1[CH:14]=[C:15]([CH:19]2[CH2:24][CH2:23][CH2:22][NH:21][CH2:20]2)[CH:16]=[CH:17][CH:18]=1.C(=O)(O)[O-].[Na+]>C1C=CC=CC=1>[F:26][C:12]([F:11])([F:25])[C:13]1[CH:14]=[C:15]([CH:19]2[CH2:24][CH2:23][CH2:22][N:21]([CH:1]=[O:3])[CH2:20]2)[CH:16]=[CH:17][CH:18]=1
Reactant: O=CO
Reactant: FC(F)(F)c1cccc(C2CCCNC2)c1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: c1ccccc1
Solvent: CC(=O)OC(C)=O
Product: O=CN1CCCC(c2cccc(C(F)(F)F)c2)C1
Temperature: 25 °C
Reaction time: 0.25 h
Yield: 151.5 %

Procedure:
3.8 g of mixed formic acid-acetic acid anhydride were added to a solution of 9.8 g of 3-(m-trifluoromethylphenyl)-piperidine in 100 ml of anhydrous benzene and the mixture was stirred for 15 minutes at room temperature and was then poured into 100 ml of aqueous sodium bicarbonate. The mixture was extracted with ethyl acetate and the organic extracts were washed with aqueous sodium chloride, dried over magnesium sulfate and evaporated to dryness to obtain 10 g of 3-(m-trifluoromethylphenyl)-1-piperidine-carboxaldehyde in the form of a colorless resin which was used as is for the next step.
Reaction SMILES: [C:1]1([C:7]2[S:11][C:10]3[CH:12]=[CH:13][CH:14]=[CH:15][C:9]=3[C:8]=2[S:16]([NH-:19])(=[O:18])=[O:17])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[CH3:20][O:21][C:22]1[CH:27]=[C:26]([CH3:28])[N:25]=[C:24]([N:29](C2C=CC=CC=2)[C:30](=O)[O-:31])[N:23]=1.N12CCCN=C1CCCCC2.Cl>O.O1CCOCC1>[C:1]1([C:7]2[S:11][C:10]3[CH:12]=[CH:13][CH:14]=[CH:15][C:9]=3[C:8]=2[S:16]([NH:19][C:30]([NH:29][C:24]2[N:23]=[C:22]([O:21][CH3:20])[CH:27]=[C:26]([CH3:28])[N:25]=2)=[O:31])(=[O:18])=[O:17])[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1
Reactant: COc1cc(C)nc(N(C(=O)[O-])c2ccccc2)n1
Reactant: [NH-]S(=O)(=O)c1c(-c2ccccc2)sc2ccccc12
Agent: Cl
Solvent: C1COCCO1
Solvent: C1CCC2=NCCCN2CC1
Solvent: O
Product: COc1cc(C)nc(NC(=O)NS(=O)(=O)c2c(-c3ccccc3)sc3ccccc23)n1
Reaction time: 4 h
Yield: 78.2 %

Procedure:
A mixture of 1.1 g (3.8 mmol) of 2-phenylbenzo[b]thiophen-3-ylsulfonylamide, 1.0 g (3.8 mmol) of N-(4-methoxy-6-methylpyrimidin-2-yl)phenylcarbamate, 0.6 g (4 mmol) of 1.8-diazabicyclo[5.4.0]undec-7-ene and 15 ml of dioxane is stirred for 4 hours at 20°-25° C. The reaction mixture is then taken up in 100 ml of water, acidified to pH 3 by adding 2N hydrochloric acid dropwise and then extracted with 3×30 ml of ethyl acetate. The combined extracts are dried and concentrated by evaporation. The residue is crystallised from ether, affording 1.35 g (78% of theory) of N-(2-phenylbenzo[b]thiophen-3-ylsulfonyl)-N'-(4-methoxy-6-methylprimidin-2-yl)urea with a melting point of 199°-202° C.
Reaction SMILES: Cl[C:2]1[C:7]([CH:8]2[CH2:10][CH2:9]2)=[C:6]([Cl:11])[N:5]=[CH:4][N:3]=1.[CH:12]([O:15][C:16]([N:18]1[CH2:23][CH2:22][CH:21]([OH:24])[CH2:20][CH2:19]1)=[O:17])([CH3:14])[CH3:13].CC(C)([O-])C.[K+]>C1COCC1>[CH:12]([O:15][C:16]([N:18]1[CH2:19][CH2:20][CH:21]([O:24][C:2]2[C:7]([CH:8]3[CH2:10][CH2:9]3)=[C:6]([Cl:11])[N:5]=[CH:4][N:3]=2)[CH2:22][CH2:23]1)=[O:17])([CH3:14])[CH3:13]
Reactant: Clc1ncnc(Cl)c1C1CC1
Reactant: CC(C)OC(=O)N1CCC(O)CC1
Agent: CC(C)(C)[O-]
Agent: [K+]
Solvent: C1CCOC1
Product: CC(C)OC(=O)N1CCC(Oc2ncnc(Cl)c2C2CC2)CC1
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 73.7 %

Procedure:
To a solution of 4,6-dichloro-5-cyclopropyl-pyrimidine (700 mg, 3.70 mmol) and 4-hydroxy-piperidine-1-carboxylic acid isopropyl ester (636.6 mg, 3.70 mmol) in dry THF under nitrogen at 0° C., potassium tert-butoxide (1M solution in THF, 4.45 mL) was added dropwise. The reaction was stirred at rt for 30 min. The mixture was quenched with water and extracted with EtOAc (3×). The organic layer was washed with water, sat. NH4Cl and brine, followed by drying over sodium sulfate and concentration under vacuo. The resulting oil was purified by flash chromatography (0-20% EtOAc/Hexanes) to afford 4-(6-chloro-5-cyclopropyl-pyrimidin-4-yloxy)-piperidine-1-carboxylic acid isopropyl ester (0.927 g, 73.7%) as colorless oil. Exact mass calculated for C16H22ClN3O3 339.13, found 340.3 (MH+).
Reaction SMILES: Cl[C:2]1[CH:11]=[CH:10][N:9]=[C:8]2[C:3]=1[C:4]1[CH:16]=[CH:15][CH:14]=[CH:13][C:5]=1[C:6](=[O:12])[NH:7]2.[OH:17][C:18]1[CH:23]=[CH:22][C:21](NC(=O)C)=[CH:20][CH:19]=1.C(=O)([O-])[O-].[K+].[K+].C[N:35]([CH:37]=[O:38])C>CO>[O:12]=[C:6]1[C:5]2[CH:13]=[CH:14][CH:15]=[CH:16][C:4]=2[C:3]2[C:8](=[N:9][CH:10]=[CH:11][C:2]=2[O:17][C:18]2[CH:19]=[CH:20][C:21]([C:37]([NH2:35])=[O:38])=[CH:22][CH:23]=2)[NH:7]1
Reactant: CN(C)C=O
Reactant: O=c1[nH]c2nccc(Cl)c2c2ccccc12
Reactant: CC(=O)Nc1ccc(O)cc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CO
Product: NC(=O)c1ccc(Oc2ccnc3[nH]c(=O)c4ccccc4c23)cc1
Temperature: 100 °C
Reaction time: 8 h
Yield: 7 %

Procedure:
1-Chloro-5H-benzo[c][1,8]naphthyridin-6-one (30 mg, 0.13 mmol), N-(4-hydroxyphenyl)acetamide (59 mg, 0.39 mmol), and potassium carbonate (90 mg, 0.65 mmol) were suspended in DMF (2 mL), and stirred overnight at 100° C. The reaction mixture was diluted with MeOH, and filtered through a membrane. The crude product was purified via prep-LC-MS to provide 135 (3 mg, 7% yield) as a solid. LC-MS (M+H=346, obsd.=346). 1H NMR (400 MHz, d6-DMSO): δ 12.14 (s, 1H), 10.15 (s, 1H), 9.08 (d, 1H), 8.42 (d, 1H), 8.29 (d, 1H), 7.88 (t, 1H), 7.73 (m, 3H), 7.28 (d, 2H), 6.52 (d, 1H), 2.09 (s, 3H).
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[CH:6][C:5]([S:8]([CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][OH:17])(=[O:10])=[O:9])=[CH:4][CH:3]=1.[N:18]([O-])=O.[Na+].[CH3:22][N:23]([CH2:30][CH2:31][CH2:32][CH2:33][CH2:34][C:35]([O:37][CH2:38][CH2:39][CH2:40][CH3:41])=[O:36])[C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1>Cl.O>[CH2:38]([O:37][C:35]([CH2:34][CH2:33][CH2:32][CH2:31][CH2:30][N:23]([C:24]1[CH:29]=[CH:28][C:27]([N:18]=[N:1][C:2]2[CH:3]=[CH:4][C:5]([S:8]([CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][OH:17])(=[O:10])=[O:9])=[CH:6][CH:7]=2)=[CH:26][CH:25]=1)[CH3:22])=[O:36])[CH2:39][CH2:40][CH3:41]
Reactant: CCCCOC(=O)CCCCCN(C)c1ccccc1
Reactant: O=N[O-]
Reactant: Nc1ccc(S(=O)(=O)CCCCCCO)cc1
Agent: Cl
Agent: [Na+]
Solvent: O
Product: CCCCOC(=O)CCCCCN(C)c1ccc(N=Nc2ccc(S(=O)(=O)CCCCCCO)cc2)cc1
Temperature: 0 °C
Reaction time: 0.25 h
Yield: 53 %

Procedure:
A stirred suspension of (4-aminophenyl)-(6-hydroxyhexyl)sulfone (Example 5, 7.2 g, 28 mmol) in 60 mL of 10% HCl was cooled to 0° C. and treated dropwise with 2.1 g (31 mmol) of sodium nitrite in 10 mL of water. The reaction mixture was stirred for 15 minutes and 7.8 g (28 mmol) of butyl N-methyl-N-phenyl-6-aminohexanoate (Example 2) was added slowly. The resulting mixture was gradually warmed to 23° C. and then stirred for 16 hours. The precipitated solid was filtered, washed with water, and air dried. The product was purified by flash chromatography on silica gel, eluting with 20% (v/v) ethyl ether/80% dichloromethane. The eluate was concentrated at reduced pressure and the residue was recrystallized from toluene/heptane to yield 8.1 g (53%) of an orange powder.
Reaction SMILES: [CH2:1]([O:8][C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=1[NH:15][C:16](=[O:34])[NH:17][C:18]1[CH:23]=[CH:22][C:21]([CH2:24][C:25]([O:27]C(C)(C)C)=[O:26])=[CH:20][C:19]=1[O:32][CH3:33])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(O)(C(F)(F)F)=O>C(Cl)Cl>[CH2:1]([O:8][C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=1[NH:15][C:16](=[O:34])[NH:17][C:18]1[CH:23]=[CH:22][C:21]([CH2:24][C:25]([OH:27])=[O:26])=[CH:20][C:19]=1[O:32][CH3:33])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: COc1cc(CC(=O)OC(C)(C)C)ccc1NC(=O)Nc1ccccc1OCc1ccccc1
Solvent: O=C(O)C(F)(F)F
Solvent: ClCCl
Product: COc1cc(CC(=O)O)ccc1NC(=O)Nc1ccccc1OCc1ccccc1
Temperature: 25 °C
Reaction time: 3 h
Yield: 77 %

Procedure:
To a solution of tert-butyl 4-[N′-(2-benzyloxyphenyl)ureido]-3-methoxyphenylacetate (2.35 g, 5.08 mmol) in CH2Cl2 (25 mL) was added TFA (25 mL) at 0° C. After being stirred at room temperature. for 3 hr, the mixture was concentrated. The residue was dissolved in 1N NaOH and washed with Et2O. The basic water layer was poured into ice-1N HCl and the resulting mixture was extracted with CHCl3—MeOH (4:1, v/v). The extracts were washed with brine, dried over Na2SO4, and concentrated to dryness. The residue was dissolved in isopropyl ether and hexane was added to this solution until the crystallization was completed. The solid was collected to give 4-[N′-(2-benzyloxyphenyl)ureido]-3-methoxyphenylacetic acid (1.59 g, 77%) as a brownish solid. 1H-NMR (DMSO-d6) δ3.50 (s, 2H), 3.85 (s, 3H), 5.26 (s, 2H), 6.76 (d, J=8.3 Hz, 1H), 6.83-6.89 (m, 2H), 6.91 (s, 1H), 7.01 (dd, J=8.3, 2.3 Hz, 1H), 7.31 (t, J=7.3 Hz, 1H), 7.39 (t, J=7.3 Hz, 2H), 7.49 (d, J=7.3 Hz, 2H), 7.97 (d, J=8.3 Hz, 1H), 8.04 (d, J=8.3 H, 1H), 8.80 (s, 1H), 8.86 (s, 1H), 12.24 (broad s, 1H); FAB-MS m/z 407 (M++1).
Reaction SMILES: Cl[S:2]([OH:5])(=[O:4])=[O:3].C([O:8]CC)C>>[OH:3][S:2]([OH:5])(=[O:8])=[O:4].[O:3]=[S:2](=[O:5])=[O:4]
Reactant: O=S(=O)(O)Cl
Reactant: CCOCC
Product: O=S(=O)(O)O
Product: O=S(=O)=O

Procedure:
A dispersion was prepared, as described in Example 1, except substituting oleum for chlorosulfonic acid. A known volume of the dispersion was passed through a 0.2 μm Anodisc membrane, with vacuum assistance, to create the initial CNT network of desired thickness. Approximately, 50 mL of diethyl ether was added as a non-solvent, while maintaining vacuum. The SWNT network film was released from the membrane filter by dipping the coated membrane filter into a water bath. The SWNT network film floated to the surface of the water and was picked up with a substrate such as polyester or glass.
Reaction SMILES: Br[C:2]1[C:3]([NH:9][S:10]([C:13]2[CH:18]=[CH:17][CH:16]=[C:15]([Cl:19])[C:14]=2[Cl:20])(=[O:12])=[O:11])=[N:4][CH:5]=[C:6](Br)[N:7]=1.C[C:22](C)([O-:24])C.[K+].C[N:28]1[CH2:32][CH2:31][CH2:30][C:29]1=[O:33]>O1CCCC1.C(O)(=O)C.O>[Cl:20][C:14]1[C:15]([Cl:19])=[CH:16][CH:17]=[CH:18][C:13]=1[S:10]([NH:9][C:3]1[C:2]([O:24][CH2:22][C:32]2[N:28]=[C:29]([CH3:30])[O:33][CH:31]=2)=[N:7][CH:6]=[CH:5][N:4]=1)(=[O:12])=[O:11]
Reactant: O=S(=O)(Nc1ncc(Br)nc1Br)c1cccc(Cl)c1Cl
Reactant: CN1CCCC1=O
Reactant: CC(C)(C)[O-]
Agent: [K+]
Solvent: C1CCOC1
Solvent: O
Solvent: CC(=O)O
Product: Cc1nc(COc2nccnc2NS(=O)(=O)c2cccc(Cl)c2Cl)co1
Reaction time: 24 h

Procedure:
Examples 146-165 were prepared using the following procedure To a solution of N-(3,5-dibromo-2-pyrazinyl)-2,3-dichlorobenzenesulphonamide (Example 31) (0.003 g) and primary alcohol (0.026 mL of a 0.5M solution in N-methylpyrrolidinone) in N-methylpyrrolidinone (0.1 mL) was added potassium tert-butoxide (0.050 mL of a 1M solution in tetrahydrofuran). The solution was allowed to stand for 24 hours. The reaction mixture was diluted with acetic acid (0.010 mL) and water (0.10 mL) and the solvents were evaporated. The residue was redissolved in dimethylsulphoxide (0.5 mL) and purified by mass directed high pressure liquid chromatography. The solvent was evaporated to afford a solid.