Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Cl:1][C:2]1[CH:10]=[CH:9][C:8]([N+:11]([O-:13])=[O:12])=[CH:7][C:3]=1[C:4](O)=[O:5].C(Cl)(=O)C([Cl:17])=O>>[Cl:1][C:2]1[CH:10]=[CH:9][C:8]([N+:11]([O-:13])=[O:12])=[CH:7][C:3]=1[C:4]([Cl:17])=[O:5]
Reactant: O=C(O)c1cc([N+](=O)[O-])ccc1Cl
Reactant: O=C(Cl)C(=O)Cl
Product: O=C(Cl)c1cc([N+](=O)[O-])ccc1Cl
Temperature: 25 °C
Reaction time: 8 h

Procedure:
To a suspension of 2-chloro-5-nitro-benzoic acid (10 g, 49.6 mmol), oxalyl chloride was added dropwise (12.6 g, 2.0 equiv.). The resulting yellow solution was stirred at room temperature under argon overnight. The solvent was removed under vacuum to give a yellowish solid (10.8 g).
Reaction SMILES: [CH2:1]([N:8]1[C:12]([C:13]([OH:15])=O)=[C:11]([C:16]([F:19])([F:18])[F:17])[N:10]=[N:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH3:20][CH:21]([CH3:39])[CH2:22][CH2:23][NH:24][C:25]([C:27]1[N:28]=[N:29][C:30]([N:33]2[CH2:38][CH2:37][NH:36][CH2:35][CH2:34]2)=[CH:31][CH:32]=1)=[O:26]>>[CH3:20][CH:21]([CH3:39])[CH2:22][CH2:23][NH:24][C:25]([C:27]1[N:28]=[N:29][C:30]([N:33]2[CH2:38][CH2:37][N:36]([C:13]([C:12]3[N:8]([CH2:1][C:2]4[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=4)[N:9]=[N:10][C:11]=3[C:16]([F:19])([F:18])[F:17])=[O:15])[CH2:35][CH2:34]2)=[CH:31][CH:32]=1)=[O:26]
Reactant: CC(C)CCNC(=O)c1ccc(N2CCNCC2)nn1
Reactant: O=C(O)c1c(C(F)(F)F)nnn1Cc1ccccc1
Product: CC(C)CCNC(=O)c1ccc(N2CCN(C(=O)c3c(C(F)(F)F)nnn3Cc3ccccc3)CC2)nn1

Procedure:
Following the procedure of Example 9, making variations only as required to use 3-benzyl-5-trifluoromethyl-3H-[1,2,3]triazole-4-carboxylic acid in place of 2,5-dichlorobenzoic acid to react with 6-piperazin-1-yl-pyridazine-3-carboxylic acid (3-methylbutyl)amide, the title compound was obtained as a white powder (37% yield). 1H NMR (300 MHz, DMSO-d6) δ 8.04, 7.83, 7.36, 7.28, 6.99, 5.69, 3.94, 3.84, 3.70, 3.46, 1.75-1.61, 1.49, 0.91. MS (ES+) m/z 531.2 (M+1).
Reaction SMILES: [CH3:1][C:2]1[CH:3]=[CH:4][CH:5]=[C:6]2[C:10]=1[C:9](=[O:11])[CH2:8][CH2:7]2.[B-](F)(F)(F)[F:13].[B-](F)(F)(F)F.C1[N+]2(CCl)CC[N+](F)(CC2)C1>CO>[F:13][CH:8]1[CH2:7][C:6]2[C:10](=[C:2]([CH3:1])[CH:3]=[CH:4][CH:5]=2)[C:9]1=[O:11]
Reactant: F[B-](F)(F)F
Reactant: Cc1cccc2c1C(=O)CC2
Agent: F[N+]12CC[N+](CCl)(CC1)CC2
Solvent: CO
Product: Cc1cccc2c1C(=O)C(F)C2
Temperature: 25 °C
Reaction time: 0.5 h

Procedure:
To a solution of 7-methyl-1-indanone (CAS No. 39627-61-7,513 mg, 3.51 mmol) in MeOH (18 mL) was added Selectfluor™ (1.49 g, 4.21 mmol) at room temperature. The reaction mixture was heated for 2 hours under reflux. After cooling to room temperature, the solvent was evaporated under reduced pressure. The residue was treated with DCM and the insoluble matter was filtered off. The filtrate was concentrated in vacuo. The residue was dissolved in MeCN (10 mL) and 5 N HCl (5 mL). The solution was stirred at room temperature for 30 mins. After concentration of the solution in vacuo, the residue was partitioned between AcOEt and H2O. The aqueous layer was extracted with AcOEt twice. The combined organic layers were washed with brine, dried over MgSO4, filtered and concentrated in vacuo to afford the title compound (555 mg, 3.38 mmol).
Reaction SMILES: [OH:1][CH2:2][CH:3]1[CH2:8][CH2:7][CH2:6][CH2:5][NH:4]1.[Cl:9][C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=1[N:16]=[C:17]=[S:18]>O1CCCC1.C(N(CC)CC)C>[Cl:9][C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=1[NH:16][C:17]([N:4]1[CH2:5][CH2:6][CH2:7][CH2:8][CH:3]1[CH2:2][OH:1])=[S:18]
Reactant: OCC1CCCCN1
Reactant: S=C=Nc1ccccc1Cl
Solvent: C1CCOC1
Solvent: CCN(CC)CC
Product: OCC1CCCCN1C(=S)Nc1ccccc1Cl
Reaction time: 12 h

Procedure:
3.4 g 2-Hydroxymethylpiperidine in 50 ml absolute tetrahydrofuran was treated with 1 drop of triethylamine and 5 g 2-chlorophenyl isothiocyanate. After 12 hours at room temperature, the reaction solution was cooled in an ice bath. The crystals were suction filtered and recrystallised from ethyl acetate.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]=O)=[CH:4][C:3]=1[N:10]1[CH2:15][CH2:14][CH:13]([C:16]([O:18][CH3:19])=[O:17])[CH2:12][CH2:11]1.[C:20]1([C@H:26]([NH2:28])[CH3:27])[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1.C(O)(=O)C.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+]>ClCCCl>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][NH:28][C@@H:26]([C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)[CH3:27])=[CH:4][C:3]=1[N:10]1[CH2:15][CH2:14][CH:13]([C:16]([O:18][CH3:19])=[O:17])[CH2:12][CH2:11]1
Reactant: COC(=O)C1CCN(c2cc(C=O)ccc2Cl)CC1
Reactant: C[C@@H](N)c1ccccc1
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: [Na+]
Solvent: CC(=O)O
Solvent: ClCCCl
Product: COC(=O)C1CCN(c2cc(CN[C@H](C)c3ccccc3)ccc2Cl)CC1
Temperature: 25 °C
Reaction time: 20 h
Yield: 86.8 %

Procedure:
To a solution of methyl 1-(2-chloro-5-formylphenyl)piperidine-4-carboxylate 68 (0.180 g, 0.64 mmol) in DCE (3 mL) was added (R)-1-phenylethanamine (0.10 mL, 0.79 mmol), acetic acid (0.040 mL, 0.69 mmol), and NaBH(OAc)3 (0.168 g, 0.79 mmol). The reaction mixture was stirred at room temperature for 20 h, quenched with saturated NaHCO3, and diluted with EtOAc. The organic phase was washed with saturated NaHCO3 (1×), brine (1 x), dried over MgSO4, filtered, and concentrated in vacuo. Purification by flash column chromatography on silica gel (eluted with 50% to 100% EtOAc in hexanes) gave (R)-methyl 1-(2-chloro-5-((1-phenylethylamino)methyl)phenyl)piperidine-4-carboxylate 69 (0.215 g, 87% yield) as a colorless oil. Mass spectrum: calculated for C22H27ClN2O2 386.2. found 387.2 (M++1).
Reaction SMILES: [NH:1]([C:8]1[C:21]2[C:20](=[O:22])[C:19]3[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=3)[C:13](=[O:23])[C:12]=2[C:11](OS(C2C=CC(C)=CC=2)(=O)=O)=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH2:35]([NH2:39])[CH2:36][CH2:37][CH3:38]>>[NH:1]([C:8]1[C:21]2[C:20](=[O:22])[C:19]3[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=3)[C:13](=[O:23])[C:12]=2[C:11]([NH:39][CH2:35][CH2:36][CH2:37][CH3:38])=[CH:10][CH:9]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: CCCCN
Reactant: Cc1ccc(S(=O)(=O)Oc2ccc(Nc3ccccc3)c3c2C(=O)c2ccccc2C3=O)cc1
Product: CCCCNc1ccc(Nc2ccccc2)c2c1C(=O)c1ccccc1C2=O
Yield: 90 %

Procedure:
1-(anilino)-4-(n-butylamino)-anthraquinone was prepared by reaction of 1-(anilino)-4-tosyloxyanthraquinone with n-butylamine. The isolated and purified reaction product has the structure illustrated below. ##STR14## The yield was 90% and m.p. 118°-120° C. Mass spectrum, m/e 370 (M+), 327 (M-C3H7), 299 (327-CO); 1H-NMR (CD2Cl2)δ12.17 (br s, 1H), 10.78 (br s, 1H), 8.37-8.27 (m, 2H), 7.76-7.39 (m, 4H), 7.33-7.10 (m, 5H), 3.65-3.05 (m, 2H), 1.72-1.38 (m, 4H), 1.07-0.92 (t, 3H): UV/VIS max (Xylenes) 388 nm (ε4000), 598 (14 200), 642 (15 600).
Reaction SMILES: [F:1][C:2]([S:5][C:6]1[CH:11]=[CH:10][C:9](Br)=[CH:8][CH:7]=1)([F:4])[F:3].C(N(CC)CC)C.[NH2:20][C:21]1[CH:22]=[C:23]([C:27]#[CH:28])[CH:24]=[CH:25][CH:26]=1>CCOCC.[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[F:1][C:2]([S:5][C:6]1[CH:11]=[CH:10][C:9]([C:28]#[C:27][C:23]2[CH:24]=[CH:25][CH:26]=[C:21]([NH2:20])[CH:22]=2)=[CH:8][CH:7]=1)([F:4])[F:3]
Reactant: FC(F)(F)Sc1ccc(Br)cc1
Reactant: C#Cc1cccc(N)c1
Agent: [Pd]
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: CCN(CC)CC
Solvent: CCOCC
Product: Nc1cccc(C#Cc2ccc(SC(F)(F)F)cc2)c1
Temperature: 75 °C
Yield: 61.9 %

Procedure:
A multinecked flask as described in Example 1 was charged with 5.4 g (0.021 mol) of p-bromophenyl trifluoromethyl sulfide, 75 ml of dried, degassed triethylamine, 2.46 g (0.021 mol) of 3-aminophenylacetylene, 0.048 g (0.068 mmol) of bis(triphenylphosphine) palladium II chloride, 0.0148 g (0.564 mmol) of triphenylphosphine, and 0.03 g (0.157 mmol) of cuprous iodide. The reaction mixture was heated at 75° C. for 20 hours after which gas chromatography showed the reaction to be complete. The mixture was cooled to room temperature and diluted with 75 ml of ether. Filtration of the insoluble triethylamine hydrobromide salt by-product followed by concentration of the filtrate gave the crude product in near quantitative yield as an off-white solid. Short path distillation of the crude product under reduced pressure gave 3.9 g (0.013 mol, 62% yield) of the purified product as a white solid.
Reaction SMILES: [NH:1]1[C:12](=[O:13])[C:11]2[N:9]([CH3:10])[CH:8]=[N:7][C:6]=2[N:4]([CH3:5])[C:2]1=[O:3].Br[CH2:15][CH2:16][CH2:17][P:18]([O:23][CH2:24][CH3:25])(=[O:22])[O:19][CH2:20][CH3:21]>>[CH3:5][N:4]1[C:6]2[N:7]=[CH:8][N:9]([CH3:10])[C:11]=2[C:12](=[O:13])[N:1]([CH2:15][CH2:16][CH2:17][P:18](=[O:22])([O:23][CH2:24][CH3:25])[O:19][CH2:20][CH3:21])[C:2]1=[O:3]
Reactant: CCOP(=O)(CCCBr)OCC
Reactant: Cn1cnc2c1c(=O)[nH]c(=O)n2C
Product: CCOP(=O)(CCCn1c(=O)c2c(ncn2C)n(C)c1=O)OCC

Procedure:
The title substance was prepared from 0.067 mol of theobromine and 0.08 mol of diethyl 3-bromopropanephosphonate analogously to Example 32.
Reaction SMILES: [NH2:1][CH:2]=[C:3]([CH3:6])[CH:4]=O.[CH3:7][C:8]1([CH3:16])[CH2:15][C:13](=O)[CH2:12][C:10](=[O:11])[CH2:9]1.C(N(CC)CC)C>Cl.C([O-])(=O)C.[NH4+]>[CH3:6][C:3]1[CH:2]=[N:1][C:13]2[CH2:15][C:8]([CH3:7])([CH3:16])[CH2:9][C:10](=[O:11])[C:12]=2[CH:4]=1
Reactant: CC(C=O)=CN
Reactant: CC1(C)CC(=O)CC(=O)C1
Agent: CC(=O)[O-]
Agent: Cl
Agent: [NH4+]
Solvent: CCN(CC)CC
Product: Cc1cnc2c(c1)C(=O)CC(C)(C)C2
Temperature: 120 °C
Reaction time: 20 h
Yield: 41.2 %

Procedure:
A mixture of 3-amino-2-methylacrolein (8.5 g., 0.1 mol.) and dimedone (14 g., 0.1 mol.) was treated with triethylamine (5 ml.) and ammonium acetate (0.1 g.) and heated in an oil bath at 120° C with stirring for 20 hours. The cooled reaction mixture was diluted with 2N HCl (50 ml.) and extracted with ethyl acetate (2 × 50 ml.) and the extracts discarded. The aqueous solution was adjusted to pH 10.0 with sodium carbonate and extracted with ethyl acetate (3 × 50 ml.). The combined extracts were dried (MgSO4 and the solvent removed to give a residual oil which was distilled to give the title compound as a colourless oil (7.8 g., 40%) b.p. 80°/0.2 mm Hg. (RT = 2 min. 2% OV17, T=150°).
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[CH:6][C:5]([Cl:8])=[CH:4][C:3]=1[C:9]([C:11]1[CH:16]=[C:15]([Cl:17])[CH:14]=[CH:13][C:12]=1[Cl:18])=[O:10].[BH4-].[Na+]>C(O)C>[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([Cl:8])=[CH:4][C:3]=1[CH:9]([C:11]1[CH:16]=[C:15]([Cl:17])[CH:14]=[CH:13][C:12]=1[Cl:18])[OH:10]
Reactant: Nc1ccc(Cl)cc1C(=O)c1cc(Cl)ccc1Cl
Agent: [BH4-]
Agent: [Na+]
Solvent: CCO
Product: Nc1ccc(Cl)cc1C(O)c1cc(Cl)ccc1Cl
Reaction time: 18 h
Yield: 31.4 %

Procedure:
To 6.38 g of (2-amino-5-chlorophenyl)(2,5-dichlorophenyl)methanone dissolved in 50 ml of ethanol are added 2.4 g of sodium borohydride, and the mixture is left for 18 hours at room temperature. The resulting mixture is concentrated and the residue is taken up in ethyl acetate and washed with water. The organic phase is dried over anhydrous sodium sulfate and concentrated to give 2.016 g of the expected product.
Reaction SMILES: [Br:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9]2[CH:14]=[CH:13][C:12]([C:15]([C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=3[CH3:23])=[O:16])=[C:11]([Cl:24])[CH:10]=2)=[C:4]([CH2:25][O:26][CH2:27][CH2:28]O)[CH:3]=1.[C:30]1(=[O:36])[NH:34][C:33](=[O:35])[CH2:32][CH2:31]1>>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9]2[CH:14]=[CH:13][C:12]([C:15]([C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=3[CH3:23])=[O:16])=[C:11]([Cl:24])[CH:10]=2)=[C:4]([CH:3]=1)[CH2:25][O:26][CH2:27][CH2:28][N:34]1[C:33](=[O:35])[CH2:32][CH2:31][C:30]1=[O:36]
Reactant: O=C1CCC(=O)N1
Reactant: Cc1ccccc1C(=O)c1ccc(Nc2ccc(Br)cc2COCCO)cc1Cl
Product: Cc1ccccc1C(=O)c1ccc(Nc2ccc(Br)cc2COCCN2C(=O)CCC2=O)cc1Cl

Procedure:
Compound 158 (47 mg, 0.1 mmol), succinimide (14 mg, 0.14 mmol) were treated as described in the preparation of compound 219. Purification was done by flash chromatography (petroleum ether/ethyl acetate 1:1) to provide the title compound as yellow oil.
Reaction SMILES: [NH2:1][C@H:2]1[CH2:7][CH2:6][CH2:5][CH2:4][C@H:3]1[NH:8][C:9](=[O:26])[C:10]1[C:15]([C:16]([F:19])([F:18])[F:17])=[CH:14][C:13]([C:20]([F:23])([F:22])[F:21])=[CH:12][C:11]=1[O:24][CH3:25].[O:27]1[CH2:32][CH2:31][C:30](=O)[CH2:29][CH2:28]1>>[CH3:25][O:24][C:11]1[CH:12]=[C:13]([C:20]([F:21])([F:22])[F:23])[CH:14]=[C:15]([C:16]([F:19])([F:18])[F:17])[C:10]=1[C:9]([NH:8][CH:3]1[CH2:4][CH2:5][CH2:6][CH2:7][CH:2]1[NH:1][CH:30]1[CH2:31][CH2:32][O:27][CH2:28][CH2:29]1)=[O:26]
Reactant: O=C1CCOCC1
Reactant: COc1cc(C(F)(F)F)cc(C(F)(F)F)c1C(=O)N[C@@H]1CCCC[C@@H]1N
Product: COc1cc(C(F)(F)F)cc(C(F)(F)F)c1C(=O)NC1CCCCC1NC1CCOCC1

Procedure:
The title compound, off-white foam, MS: m/e=469.3 [(M+H)+], was prepared in accordance with the general method of example 11 from cis-N-(2-amino-cyclohexyl)-2-methoxy-4,6-bis-trifluoromethyl-benzamide (intermediate H) and tetrahydro-4H-pyran-4-one.
Reaction SMILES: [Br:1][C:2]1[CH:21]=[CH:20][C:19]([CH2:22][N:23]2[CH2:28][CH2:27][N:26](C(OC(C)(C)C)=O)[CH2:25][CH2:24]2)=[CH:18][C:3]=1[C:4]([NH:6][CH2:7][C:8]12[CH2:17][CH:12]3[CH2:13][CH:14]([CH2:16][CH:10]([CH2:11]3)[CH2:9]1)[CH2:15]2)=[O:5].[ClH:36]>CO.O1CCOCC1>[ClH:36].[Br:1][C:2]1[CH:21]=[CH:20][C:19]([CH2:22][N:23]2[CH2:28][CH2:27][NH:26][CH2:25][CH2:24]2)=[CH:18][C:3]=1[C:4]([NH:6][CH2:7][C:8]12[CH2:9][CH:10]3[CH2:16][CH:14]([CH2:13][CH:12]([CH2:11]3)[CH2:17]1)[CH2:15]2)=[O:5]
Reactant: CC(C)(C)OC(=O)N1CCN(Cc2ccc(Br)c(C(=O)NCC34CC5CC(CC(C5)C3)C4)c2)CC1
Agent: Cl
Solvent: CO
Solvent: C1COCCO1
Product: O=C(NCC12CC3CC(CC(C3)C1)C2)c1cc(CN2CCNCC2)ccc1Br
Temperature: 25 °C
Reaction time: 14 h

Procedure:
2-Bromo-5-(4-[{1,1-dimethylethyl}oxycarbonyl]-piperazin-1-yl)methyl-N-(tricyclo[3.3.1.13,7]dec-1-ylmethyl)-benzamide (Example 65b, 0.40 g) was dissolved in methanol (15 ml), and 4N HCl in dioxane (3 ml) added. The mixture was stirred at room temperature for 14 h. The solvent was removed under vacuum and the resulting solid was triturated with ether to afford the title compound as a white powder (0.23 g).
Reaction SMILES: [NH2:1][C@@H:2]([CH2:10][C:11]1[CH:12]=[N:13][C:14]([Br:17])=[CH:15][CH:16]=1)[C:3]([O:5]C(C)(C)C)=[O:4].C(O)(C(F)(F)F)=O>C(Cl)Cl>[NH2:1][C@@H:2]([CH2:10][C:11]1[CH:12]=[N:13][C:14]([Br:17])=[CH:15][CH:16]=1)[C:3]([OH:5])=[O:4]
Reactant: CC(C)(C)OC(=O)[C@@H](N)Cc1ccc(Br)nc1
Solvent: O=C(O)C(F)(F)F
Solvent: ClCCl
Product: N[C@@H](Cc1ccc(Br)nc1)C(=O)O
Reaction time: 0.5 h
Yield: 76.8 %

Procedure:
(S)-tert-Butyl 2-amino-3-(6-bromopyridin-3-yl)propanoate (4 g) was dissolved in DCM (20 mL) and the solution obtained was treated with TFA (20 mL). The mixture was stirred for 0.5 h, concentrated in vacuo, azeotroping with toluene, and loaded onto an NH2-silica cartridge. Non acidic impurities were eluted with acetonitrile, then the desired product was eluted with 10% acetic acid in acetonitrile. Solvent was removed in vacuo to give the sub-title compound (2.5 g).
Reaction SMILES: [N:1]1[C:10]2[C:5](=[CH:6][C:7]([C:11]([OH:13])=O)=[CH:8][CH:9]=2)[CH:4]=[CH:3][CH:2]=1.[NH2:14][C:15]1[CH:16]=[C:17]([NH:22][C:23](=[O:32])[C:24]2[CH:29]=[CH:28][C:27]([C:30]#[N:31])=[CH:26][CH:25]=2)[CH:18]=[CH:19][C:20]=1[Cl:21]>>[Cl:21][C:20]1[CH:19]=[CH:18][C:17]([NH:22][C:23](=[O:32])[C:24]2[CH:29]=[CH:28][C:27]([C:30]#[N:31])=[CH:26][CH:25]=2)=[CH:16][C:15]=1[NH:14][C:11]([C:7]1[CH:6]=[C:5]2[C:10](=[CH:9][CH:8]=1)[N:1]=[CH:2][CH:3]=[CH:4]2)=[O:13]
Reactant: O=C(O)c1ccc2ncccc2c1
Reactant: N#Cc1ccc(C(=O)Nc2ccc(Cl)c(N)c2)cc1
Product: N#Cc1ccc(C(=O)Nc2ccc(Cl)c(NC(=O)c3ccc4ncccc4c3)c2)cc1
Yield: 18 %

Procedure:
Using an analogous procedure to that described in Example 3, quinoline-6-carboxylic acid was reacted with N-(3-amino-4-chlorophenyl)-4-cyanobenzamide. The crude reaction product was purified by column chromatography on silica using a 97:3 mixture of methylene chloride and methanol as eluent. There was thus obtained the title compound in 18% yield; NMR Spectrum: (DMSOd6) 7.58 (d, 1H), 7.62 (m, 1H), 7.77 (m, 1H), 8.01 (d, 2H), 8.12 (t, 4H), 8.28 (d, 2H), 8.56 (d, 1H), 8.67 (s, 1H), 9.01 (d, 1H), 10.34 (s, 1H), 10.67 (s, 1H); Mass Spectrum: M−H− 425.
Reaction SMILES: [NH2:1][C:2]1[C:3]([C:22]2[CH:27]=[CH:26][C:25]([Cl:28])=[CH:24][C:23]=2[Cl:29])=[N:4][C:5]([NH:8][CH2:9][CH2:10][NH:11][C:12]2[CH:17]=[CH:16][C:15]([N+:18]([O-:20])=[O:19])=[C:14]([NH2:21])[N:13]=2)=[N:6][CH:7]=1.[C:30](OC(=O)C)(=[O:32])[CH3:31]>C1COCC1>[NH2:21][C:14]1[N:13]=[C:12]([NH:11][CH2:10][CH2:9][NH:8][C:5]2[N:4]=[C:3]([C:22]3[CH:27]=[CH:26][C:25]([Cl:28])=[CH:24][C:23]=3[Cl:29])[C:2]([NH:1][C:30](=[O:32])[CH3:31])=[CH:7][N:6]=2)[CH:17]=[CH:16][C:15]=1[N+:18]([O-:20])=[O:19]
Reactant: Nc1cnc(NCCNc2ccc([N+](=O)[O-])c(N)n2)nc1-c1ccc(Cl)cc1Cl
Reactant: CC(=O)OC(C)=O
Solvent: C1CCOC1
Product: CC(=O)Nc1cnc(NCCNc2ccc([N+](=O)[O-])c(N)n2)nc1-c1ccc(Cl)cc1Cl

Procedure:
1 mmol of [5-amino-4-(2,4-dichlorophenyl)pyrimidin-2-yl]{2-[(6-amino-5-nitro(2-pyridyl))amino]ethyl}amine and 1 mmol of acetic anhydride were stirred at room temperature for four hours in THF. The reaction mixture was concentrated in vacuo and diluted with water and ethyl acetate. The solution was extracted three times with ethyl acetate, dried over sodium sulfate, and purified by column chromatography eluting with 5-10% methanol/methylene chloride to obtain N-[2-({2-[(6-amino-5-nitro(2-pyridyl))amino]ethyl}amino)-4-(2,4-dichlorophenyl)pyrimidin-5-yl]acetamide.
Reaction SMILES: [O:1]1[CH:6]([C:7]([NH:9][C:10]2[CH:31]=[CH:30][C:13]([CH2:14][N:15]3[C:23]4[C:18](=[CH:19][CH:20]=[CH:21][CH:22]=4)[C:17]([CH2:24][C:25]([O:27]CC)=[O:26])=[N:16]3)=[CH:12][CH:11]=2)=[O:8])[CH2:5][O:4][C:3]2[CH:32]=[CH:33][CH:34]=[CH:35][C:2]1=2.O.[OH-].[Li+].O.Cl>O1CCCC1>[O:1]1[CH:6]([C:7]([NH:9][C:10]2[CH:31]=[CH:30][C:13]([CH2:14][N:15]3[C:23]4[C:18](=[CH:19][CH:20]=[CH:21][CH:22]=4)[C:17]([CH2:24][C:25]([OH:27])=[O:26])=[N:16]3)=[CH:12][CH:11]=2)=[O:8])[CH2:5][O:4][C:3]2[CH:32]=[CH:33][CH:34]=[CH:35][C:2]1=2
Reactant: CCOC(=O)Cc1nn(Cc2ccc(NC(=O)C3COc4ccccc4O3)cc2)c2ccccc12
Agent: Cl
Agent: [Li+]
Agent: [OH-]
Solvent: O
Solvent: C1CCOC1
Product: O=C(O)Cc1nn(Cc2ccc(NC(=O)C3COc4ccccc4O3)cc2)c2ccccc12
Yield: 96.5 %

Procedure:
Ethyl 2-[1-[4-(2,3-dihydrobenzo[b][1,4]dioxin-2-carboxamido)benzyl]-1H-indazol-3-yl]acetate (160 mg, 0.339 mmol) was dissolved in tetrahydrofuran (20 mL), and in an ice bath, 10 mL aqueous solution dissolving lithium hydroxide monohydrate (43 mg, 1.02 mmol) was added. It was reacted at room temperature for 3 h, and the reaction was monitored to be complete by TLC. Water was added into the system, and adjusted to pH≈3-4 with diluted hydrochloric acid. A solid precipitated, which was filtered and dried to obtain a white solid 145 mg, at a yield of 96.5%.
Reaction SMILES: [C:1]([C:5]1[S:6][C:7]2[CH:13]=[C:12]([N+:14]([O-:16])=[O:15])[C:11](Cl)=[CH:10][C:8]=2[N:9]=1)([CH3:4])([CH3:3])[CH3:2].[NH:18]1[CH2:23][CH2:22][NH:21][CH2:20][CH2:19]1>CS(C)=O>[C:1]([C:5]1[S:6][C:7]2[CH:13]=[C:12]([N+:14]([O-:16])=[O:15])[C:11]([N:18]3[CH2:23][CH2:22][NH:21][CH2:20][CH2:19]3)=[CH:10][C:8]=2[N:9]=1)([CH3:4])([CH3:3])[CH3:2]
Reactant: CC(C)(C)c1nc2cc(Cl)c([N+](=O)[O-])cc2s1
Reactant: C1CNCCN1
Solvent: CS(C)=O
Product: CC(C)(C)c1nc2cc(N3CCNCC3)c([N+](=O)[O-])cc2s1
Temperature: 0 °C

Procedure:
A solution of 13.5 g of 2-tert-butyl-5-chloro-6-nitrobenzothiazole described in Example 5, and 40 g of anhydrous piperazine in 100 ml of dimethylsulphoxide is heated at 140° for 2 hours, cooled and poured into ice-water. The yellow solid is filtered, washed with water and dried at 80° to yield 2-tert-butyl-6-nitro-5-[piperazin-1-yl]benzothiazole, melting at 144°-146°.
Reaction SMILES: Br[C:2]1[CH:14]=[CH:13][CH:12]=[CH:11][C:3]=1[O:4][C:5]1[N:10]=[CH:9][CH:8]=[CH:7][N:6]=1.[F:15][C:16]1[CH:21]=[C:20](B2OC(C)(C)C(C)(C)O2)[CH:19]=[CH:18][C:17]=1[C:31]1[CH:32]=[N:33][C:34]([NH2:37])=[N:35][CH:36]=1>>[F:15][C:16]1[CH:21]=[C:20]([C:2]2[CH:14]=[CH:13][CH:12]=[CH:11][C:3]=2[O:4][C:5]2[N:10]=[CH:9][CH:8]=[CH:7][N:6]=2)[CH:19]=[CH:18][C:17]=1[C:31]1[CH:36]=[N:35][C:34]([NH2:37])=[N:33][CH:32]=1
Reactant: CC1(C)OB(c2ccc(-c3cnc(N)nc3)c(F)c2)OC1(C)C
Reactant: Brc1ccccc1Oc1ncccn1
Product: Nc1ncc(-c2ccc(-c3ccccc3Oc3ncccn3)cc2F)cn1

Procedure:
The title compound was prepared in a manner similar to that described in Example 88 using 2-(2-bromophenoxy)pyrimidine and 5-(2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)pyrimidin-2-amine. MS (ESI): mass calcd. for C20H14FN5O, 359.12; m/z found, 360.1 [M+H]+. 1H NMR (500 MHz, DMSO-d6) δ 8.58 (d, J=4.8, 2H), 8.43 (d, J=1.4, 2H), 7.58-7.46 (m, 3H), 7.42-7.27 (m, 4H), 7.20 (t, J=4.8, 1H), 6.88 (s, 2H).
Reaction SMILES: [CH3:1][C:2]1[CH:7]=[CH:6][N:5]2[CH:8]=[C:9]([CH2:11][C@@H:12]3[CH2:17][CH2:16][CH2:15][CH2:14][N:13]3[C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[N:10]=[C:4]2[N:3]=1.C1C(=O)N([Cl:32])C(=O)C1>C(Cl)Cl>[Cl:32][C:8]1[N:5]2[CH:6]=[CH:7][C:2]([CH3:1])=[N:3][C:4]2=[N:10][C:9]=1[CH2:11][C@@H:12]1[CH2:17][CH2:16][CH2:15][CH2:14][N:13]1[C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19]
Reactant: Cc1ccn2cc(C[C@@H]3CCCCN3C(=O)OC(C)(C)C)nc2n1
Reactant: O=C1CCC(=O)N1Cl
Solvent: ClCCl
Product: Cc1ccn2c(Cl)c(C[C@@H]3CCCCN3C(=O)OC(C)(C)C)nc2n1
Temperature: 25 °C
Reaction time: 1.5 h
Yield: 43.4 %

Procedure:
To a solution of 1,1-dimethylethyl (2S)-2-[(7-methylimidazo[1,2-a]pyrimidin-2-yl)methyl]-1-piperidinecarboxylate (0.350 g, 0.53 mmol) in DCM (5 ml) was added NCS (0.071 g, 0.53 mmol) and the reaction mixture was stirred for 1.5 h at rt. The solvent was evaporated and the residue purified by cromatography on silica gel (Biotage, NH phase 25+M, Cy/EtOAc from 100/0 to 50/50). Collected fractions gave the title compound (0.085 g, 0.23 mmol, 44% yield) as a colourless solid. UPLC: rt=0.70, peak observed: 365 (M+1, 100%) and 367 (M+1, 33%). C18H25ClN4O2 requires 365.
Reaction SMILES: [N+:1]([C:4]1[CH:13]=[CH:12][C:7]2[B:8]([OH:11])[O:9][CH2:10][C:6]=2[CH:5]=1)([O-])=O.Cl>CO.[Zn]>[NH2:1][C:4]1[CH:13]=[CH:12][C:7]2[B:8]([OH:11])[O:9][CH2:10][C:6]=2[CH:5]=1
Reactant: O=[N+]([O-])c1ccc2c(c1)COB2O
Agent: Cl
Agent: [Zn]
Solvent: CO
Product: Nc1ccc2c(c1)COB2O
Temperature: 25 °C
Reaction time: 2.5 h
Yield: 83 %

Procedure:
To a solution of 5-nitrobenzo[c][1,2]oxaborol-1(3H)-ol (CII) (360 mg, 2.01 mmol) in MeOH (25 mL) was added Zn dust (1.31 g, 20.11 mmol) and 2 M HCl (30 mL, 60.33 mmol). The reaction mixture was stirred at room temperature for 2.5 h before saturating with 5% aq. NaHCO3 (40 mL). The solids were filtered and filtrate was concentrated under reduce pressure to about 50 mL. The residue was diluted with EtOAc and the phases were separated. The organic layer was washed with brine, dried over MgSO4, and concentrated in vacuo to give 5-aminobenzo[c][1,2]oxaborol-1(3H)-ol (CIII) as a brown oil (250 mg, 1.68 mmol, 83% yield, 80% purity). ESIMS found for C7H8BNO2 m/z 149.9 (M+H). The crude product was used without further purification for coupling.
Reaction SMILES: [CH2:1]1[O:12][C:4]([CH:6]2[CH2:10][CH2:9][CH2:8][C:7]2=[O:11])(O)[O:3][CH2:2]1.C([N:15](CC)CC)C.ClC(OCC)=O>C(Cl)(Cl)Cl>[CH2:1]1[O:12][C:4]([CH:6]2[CH2:10][CH2:9][CH2:8][C:7]2=[O:11])([NH2:15])[O:3][CH2:2]1
Reactant: O=C1CCCC1C1(O)OCCO1
Reactant: CCN(CC)CC
Agent: CCOC(=O)Cl
Solvent: ClC(Cl)Cl
Product: NC1(C2CCCC2=O)OCCO1
Reaction time: 0.5 h

Procedure:
To a stirred, cold (0° C.) solution of 1.72 g (0.01 mole) of 2-oxocyclopentanecarboxylic acid ethylene ketal in 35 ml of chloroform was added first 1.11 g (0.011 mole) of triethylamine and then 1.085 g (0.01 mole) of ethyl chloroformate, the latter being added in dropwise fashion. After stirring for 30 minutes, dry ammonia gas was bubbled in over about 5 minutes. A white solid separated while the mixture was stirred at about 0° C. for 30 minutes. The solid was separated by filtration and washed with chloroform, and the combined washings and filtrate were evaporated to provide a white solid residue of 2-oxocyclopentanecarboxamide ethylene ketal. Infrared spectral analysis showed the product to be identical to that obtained in Example 1.