Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: C[O:2][C:3]([C:5]1[C:6](=[O:23])[O:7][C:8]2[CH:14]=[C:13]([O:15][CH2:16][C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=3)[CH:12]=[CH:11][C:9]=2[CH:10]=1)=[O:4].[OH-].[Na+].Cl.O>C(O)C>[CH2:16]([O:15][C:13]1[CH:12]=[CH:11][C:9]2[CH:10]=[C:5]([C:3]([OH:4])=[O:2])[C:6](=[O:23])[O:7][C:8]=2[CH:14]=1)[C:17]1[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=1
Reactant: COC(=O)c1cc2ccc(OCc3ccccc3)cc2oc1=O
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: CCO
Solvent: O
Product: O=C(O)c1cc2ccc(OCc3ccccc3)cc2oc1=O
Reaction time: 0.17 h
Yield: 94.9 %

Procedure:
The compound 1 (0.1 g, 0.32 mmol) is dissolved in ethanol (0.5 mL), and 10% of sodium hydroxide aqueous solution (0.5 mL) is added into. The resulting mixture is reacted for 1 hour with reflux. After cooling, the strong hydrochloric acid (0.3 mL) is added and followed by stirring for 10 minutes. 5 mL of water is added, and produced solid is obtained by filtration. The filter cake is washed with water, followed by drying to obtain 0.09 g of the captioned compound, yield: 90%. m.p. 196-197° C. 1H NMR (DMSO-d6): δ=5.25(s, 2 H), 7.08(dd, J=2.2 Hz, 8.8 Hz, 1H), 7.12(d, J=2.2 Hz, 1H), 7.30-7.50(m, 5H), 7.83(d, J=8.8 Hz, 1H), 8.73(s, 1H); Elements Analysis, C17H12O5 (296): Calculated C, 68.92; H, 4.05; Found C, 68.50; H, 4.12; IR(KBr) : 3054.7, 1747.2, 1677.8, 1600.7, 1556.3, 1421.3, 1378.9, 1257.4, 1209.2, 1120.2, 732.8 cm−1; EI-MS(m/z): 296(4, M+), 91(100).
Reaction SMILES: [C:1]([O:5][C:6](=[O:34])[NH:7][C:8]([CH3:33])([CH3:32])[CH2:9][NH:10][C:11]1[C:20]2[C:15](=[CH:16][C:17]([O:21][CH2:22][C:23]3[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=3)=[CH:18][CH:19]=2)[N:14]=[CH:13][C:12]=1[N+:29]([O-])=O)([CH3:4])([CH3:3])[CH3:2].[H][H]>[Pt].C(#N)C>[C:1]([O:5][C:6](=[O:34])[NH:7][C:8]([CH3:33])([CH3:32])[CH2:9][NH:10][C:11]1[C:20]2[C:15](=[CH:16][C:17]([O:21][CH2:22][C:23]3[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=3)=[CH:18][CH:19]=2)[N:14]=[CH:13][C:12]=1[NH2:29])([CH3:4])([CH3:2])[CH3:3]
Reactant: CC(C)(CNc1c([N+](=O)[O-])cnc2cc(OCc3ccccc3)ccc12)NC(=O)OC(C)(C)C
Reactant: [H][H]
Agent: [Pt]
Solvent: CC#N
Product: CC(C)(CNc1c(N)cnc2cc(OCc3ccccc3)ccc12)NC(=O)OC(C)(C)C
Yield: 95.8 %

Procedure:
tert-Butyl[2-(7-benzyloxy-3-nitroquinolin-4-ylamino)-1,1-dimethylethyl]carbamate (6.74 g), 5% platinum on carbon (1.02 g), and acetonitrile (125 mL) were combined. The mixture was shaken overnight under 50 psi (3.4×105 Pa) of hydrogen. The reaction was filtered through CELITE filter agent and the filtrate was concentrated under reduced pressure to give 6.04 g of tert-butyl[2-(3-amino-7-benzyloxyquinolin-4-ylamino)-1,1-dimethylethyl]carbamate as an orange foam.
Reaction SMILES: [C:1]([O:5][C:6]([N:8]1[CH2:20][C@@H:19]([CH3:21])[N:18]2[C@H:10]([CH2:11][C:12]3[C:17]2=[N:16][C:15]([CH2:22][CH3:23])=[C:14]([CH2:24][OH:25])[CH:13]=3)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[H-].[Na+].Br[CH2:29][CH:30]1[CH2:32][CH2:31]1>>[C:1]([O:5][C:6]([N:8]1[CH2:20][C@@H:19]([CH3:21])[N:18]2[C@H:10]([CH2:11][C:12]3[C:17]2=[N:16][C:15]([CH2:22][CH3:23])=[C:14]([CH2:24][O:25][CH2:29][CH:30]2[CH2:32][CH2:31]2)[CH:13]=3)[CH2:9]1)=[O:7])([CH3:2])([CH3:3])[CH3:4]
Reactant: CCc1nc2c(cc1CO)C[C@@H]1CN(C(=O)OC(C)(C)C)C[C@@H](C)N21
Reactant: BrCC1CC1
Agent: [H-]
Agent: [Na+]
Product: CCc1nc2c(cc1COCC1CC1)C[C@@H]1CN(C(=O)OC(C)(C)C)C[C@@H](C)N21

Procedure:
This compound was prepared in analogy to example 1, intermediate d) from (4R,9aR)-6-ethyl-7-hydroxymethyl-4-methyl-3,4,9,9a-tetrahydro-1H-2,4a,5-triaza-fluorene-2-carboxylic acid tert-butyl ester, sodium hydride and (bromomethyl)cyclopropane.
Reaction SMILES: [CH:1]1([CH2:6][OH:7])[CH2:5][CH2:4][CH2:3][CH2:2]1.[CH3:8][S:9](Cl)(=[O:11])=[O:10].C(N(CC)CC)C>CN(C)C1C=CN=CC=1.C(Cl)Cl>[CH3:8][S:9]([O:7][CH2:6][CH:1]1[CH2:5][CH2:4][CH2:3][CH2:2]1)(=[O:11])=[O:10]
Reactant: OCC1CCCC1
Reactant: CS(=O)(=O)Cl
Agent: CN(C)c1ccncc1
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: CS(=O)(=O)OCC1CCCC1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
At room temperature (r.t.) to a solution of cyclopentanemethanol (0.2 g, 2 mmol, Aldrich, Cat. No. 103985) in methylene chloride (5 mL, 80 mmol) was added methanesulfonyl chloride (180 uL, 2.4 mmol), followed by triethylamine (330 uL, 2.4 mmol), and 4-dimethylaminopyridine (24 mg, 0.20 mmol). The mixture was stirred at r.t. overnight. It was diluted with methylene chloride, washed with water, brine; dried over Na2SO4. After filtration the filtrate was concentrated to yield 0.39 g of the product which was directly used in the next step reaction without further purification.
Reaction SMILES: [C:1]([CH2:9][CH2:10][C:11]([OH:13])=O)(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C1N=CN(C(N2C=NC=C2)=O)C=1.Cl.[CH3:27][O:28][C:29](=[O:35])[C@@H:30]1[CH2:34][CH2:33][CH2:32][NH:31]1>O1CCCC1>[CH3:27][O:28][C:29](=[O:35])[C@@H:30]1[CH2:34][CH2:33][CH2:32][N:31]1[C:11](=[O:13])[CH2:10][CH2:9][C:1](=[O:8])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: O=C(O)CCC(=O)c1ccccc1
Reactant: COC(=O)[C@@H]1CCCN1
Agent: Cl
Agent: O=C(n1ccnc1)n1ccnc1
Solvent: C1CCOC1
Product: COC(=O)[C@@H]1CCCN1C(=O)CCC(=O)c1ccccc1
Temperature: 25 °C
Reaction time: 60 h

Procedure:
A mixture of 3.56 g. of 3-benzoylpropionic acid and 3.24 g. of N,N-carbonyldiimidazole in 30 ml. of tetrahydrofuran is stirred at room temperature for 30 minutes. A 3.32 g. portion of L-proline methyl ester hydrochloride is added and the mixture is stirred at room temperature for 2.5 days. The solvent is removed in vacuo. Water and dichloromethane are added to the residue and the organic layer is separated, washed with water, then with 0.1 N hydrochloric acid and dried over magnesium sulfate. The solvent is removed in vacuo, giving 5.0 g. of the desired product as off-white crystals, m.p. 66°-70° C.
Reaction SMILES: [CH3:1][C:2]1[CH:3]=[C:4]([OH:15])[C:5]([C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][N:10]=2)=[N:6][C:7]=1[CH3:8].[CH2:16]([O:23][C:24]1[CH:33]=[C:32]2[C:27]([C:28](Cl)=[CH:29][CH:30]=[N:31]2)=[CH:26][C:25]=1[O:35][CH3:36])[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1.C(=O)([O-])[O-].[Cs+].[Cs+].O>CN(C)C1C=CN=CC=1.CS(C)=O>[CH2:16]([O:23][C:24]1[CH:33]=[C:32]2[C:27]([C:28]([O:15][C:4]3[C:5]([C:9]4[CH:14]=[CH:13][CH:12]=[CH:11][N:10]=4)=[N:6][C:7]([CH3:8])=[C:2]([CH3:1])[CH:3]=3)=[CH:29][CH:30]=[N:31]2)=[CH:26][C:25]=1[O:35][CH3:36])[C:17]1[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=1
Reactant: COc1cc2c(Cl)ccnc2cc1OCc1ccccc1
Reactant: Cc1cc(O)c(-c2ccccn2)nc1C
Agent: CN(C)c1ccncc1
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: CS(C)=O
Solvent: O
Product: COc1cc2c(Oc3cc(C)c(C)nc3-c3ccccn3)ccnc2cc1OCc1ccccc1
Temperature: 130 °C
Reaction time: 8 h
Yield: 73.1 %

Procedure:
5,6-Dimethyl-3-hydroxy-[2,2′]bipyridine (241 mg), 7-benzyloxy-4-chloro-6-methoxyquinoline (1.08 g), 4-dimethylaminopyridine (441 mg), and cesium carbonate (1.18 g) were suspended in dimethyl sulfoxide (6 ml), and the mixture was stirred at 130° C. overnight. The reaction solution was cooled to room temperature, water was then added to the reaction solution, and the mixture was extracted with chloroform. The chloroform layer was washed with saturated brine and was dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure, and the residue was purified by column chromatography using chloroform-methanol to give the title compound (408 mg, yield 73%).
Reaction SMILES: Cl[C:2]1[C:3]([NH:9][C:10]([NH:12][C:13](=[O:20])[C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)=[S:11])=[N:4][CH:5]=[C:6]([Cl:8])[CH:7]=1.C[O-].[Na+].O>CN1C(=O)CCC1>[Cl:8][C:6]1[CH:7]=[C:2]2[S:11][C:10]([NH:12][C:13](=[O:20])[C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=3)=[N:9][C:3]2=[N:4][CH:5]=1
Reactant: O=C(NC(=S)Nc1ncc(Cl)cc1Cl)c1ccccc1
Agent: C[O-]
Agent: [Na+]
Solvent: CN1CCCC1=O
Solvent: O
Product: O=C(Nc1nc2ncc(Cl)cc2s1)c1ccccc1
Temperature: 120 °C
Yield: 7.9 %

Procedure:
To N-(3,5-dichloropyridin-2-ylcarbamothioyl)benzamide (5.2 g, 16 mmol) in NMP (40 mL) was added sodium methoxide (1.73 g, 32.0 mmol). The mixture was heated in a 120° C. oil bath for 4 h, cooled to ambient temperature and poured into water. The solids were collected by filtration and purified on by silica gel chromatography (0-5% (9:1 MeOH:NH4OH)/chloroform) to give N-(6-chlorothiazolo[4,5-b]pyridin-2-yl)benzamide (364 mg, 1.256 mmol, 7.85% yield). 1H NMR (400 MHz, DMSO-d6) δ ppm 13.16 (br. s., 1H) 8.48-8.58 (m, 2H) 8.13-8.23 (m, 2H) 7.61-7.69 (m, 1H) 7.56 (t, J=7.53 Hz, 2H). MS (LC/MS) R.T.=2.8; [M+H]+=290.1.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]2[C:15]3[C:16]4[CH2:22][CH2:21][CH2:20][NH:19][CH2:18][C:17]=4[S:23][C:14]=3[N:13]=[CH:12][N:11]=2)[CH:5]=[CH:6][C:7]=1[Cl:8].Cl.[CH3:25][N:26]([CH:33]([CH3:35])[CH3:34])[CH2:27]/[CH:28]=[CH:29]/[C:30](O)=[O:31]>>[Cl:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]2[C:15]3[C:16]4[CH2:22][CH2:21][CH2:20][N:19]([C:30](=[O:31])/[CH:29]=[CH:28]/[CH2:27][N:26]([CH3:25])[CH:33]([CH3:35])[CH3:34])[CH2:18][C:17]=4[S:23][C:14]=3[N:13]=[CH:12][N:11]=2)[CH:5]=[CH:6][C:7]=1[Cl:8]
Reactant: CC(C)N(C)C/C=C/C(=O)O
Reactant: Clc1ccc(Nc2ncnc3sc4c(c23)CCCNC4)cc1Cl
Agent: Cl
Product: CC(C)N(C)C/C=C/C(=O)N1CCCc2c(sc3ncnc(Nc4ccc(Cl)c(Cl)c4)c23)C1

Procedure:
The title compound was synthesized in analogy to Example 89 from N-(3,4-dichlorophenyl)-6,7,8,9-tetrahydro-5H-pyrimido[5′,4′:4,5]thieno[2,3-c]azepin-4-amine from Example 82A (100 mg, 0.27 mmol) and (2E)-4-[methyl(1-methylethyl)amino]but-2-enoic acid hydrochloride from Example 2A (74 mg, 0.38 mmol) to yield 71 mg (50%).
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[CH:4][CH:5]=[C:6]2[C:10]=1[NH:9][C:8]([C:11](=[O:14])[CH2:12][CH3:13])=[C:7]2[CH3:15].[S:16]1[CH:20]=[CH:19][CH:18]=[C:17]1[S:21](Cl)(=[O:23])=[O:22]>N1C=CC=CC=1>[CH3:15][C:7]1[C:6]2[C:10](=[C:2]([NH:1][S:21]([C:17]3[S:16][CH:20]=[CH:19][CH:18]=3)(=[O:23])=[O:22])[CH:3]=[CH:4][CH:5]=2)[NH:9][C:8]=1[C:11](=[O:14])[CH2:12][CH3:13]
Reactant: CCC(=O)c1[nH]c2c(N)cccc2c1C
Reactant: O=S(=O)(Cl)c1cccs1
Solvent: c1ccncc1
Product: CCC(=O)c1[nH]c2c(NS(=O)(=O)c3cccs3)cccc2c1C
Temperature: 25 °C
Reaction time: 2 h
Yield: 64.9 %

Procedure:
To a mixture of 1-(7-amino-3-methyl-1H-indol-2-yl)propan-1-one (0.17 g) and pyridine (6 mL) was added thiophene-2-sulfonyl chloride (0.18 g) at 0° C., and the mixture was stirred at room temperature for 2 hr. The reaction mixture was concentrated, 10% aqueous citric acid solution was added, and the resulting crystals were filtrated, washed with water and dried. The obtained crystals were subjected to silica gel column chromatography, and eluted with ethyl acetate. The eluate was treated with activated carbon and concentrated to give the title compound (0.19 g, yield 65%) as colorless crystals. The crystals were recrystallized from ethyl acetate-hexane. melting point >185° C. (decomposition).
Reaction SMILES: [C:1]([O:5][C:6](=[O:17])[CH2:7][O:8][C:9]1[CH:14]=[CH:13][CH:12]=[C:11]([Cl:15])[C:10]=1I)([CH3:4])([CH3:3])[CH3:2].[C:18]([C:20]1[CH:25]=[CH:24][CH:23]=[C:22]([S:26]([CH2:29][CH2:30][CH3:31])(=[O:28])=[O:27])[CH:21]=1)#[CH:19]>>[C:1]([O:5][C:6](=[O:17])[CH2:7][O:8][C:9]1[CH:14]=[CH:13][CH:12]=[C:11]([Cl:15])[C:10]=1[C:19]#[C:18][C:20]1[CH:25]=[CH:24][CH:23]=[C:22]([S:26]([CH2:29][CH2:30][CH3:31])(=[O:28])=[O:27])[CH:21]=1)([CH3:4])([CH3:3])[CH3:2]
Reactant: C#Cc1cccc(S(=O)(=O)CCC)c1
Reactant: CC(C)(C)OC(=O)COc1cccc(Cl)c1I
Product: CCCS(=O)(=O)c1cccc(C#Cc2c(Cl)cccc2OCC(=O)OC(C)(C)C)c1

Procedure:
Following the general method as outlined in Intermediate 79, starting from (3-chloro-2-iodo-phenoxy)-acetic acid tert-butyl ester (Intermediate 94) and 1-ethynyl-3-(propane-1-sulfonyl)-benzene (Intermediate 42), the title compound was obtained a brown sticky solid after purification by flash column chromatography (silica), eluting with cyclohexane containing increasing amounts of EtOAc.
Reaction SMILES: [C:1]([C:3]1[C:4](=[O:18])[NH:5][C:6](=[O:17])[N:7]([CH:16]=1)[C@@H:8]1[O:14][C@H:11]([CH2:12][OH:13])[C@@H:10]([F:15])[CH2:9]1)#[CH:2].[CH3:19][C:20]([CH3:25])([CH3:24])[C:21](Cl)=[O:22]>N1C=CC=CC=1>[C:1]([C:3]1[C:4](=[O:18])[NH:5][C:6](=[O:17])[N:7]([CH:16]=1)[C@@H:8]1[O:14][C@H:11]([CH2:12][O:13][C:21](=[O:22])[C:20]([CH3:25])([CH3:24])[CH3:19])[C@@H:10]([F:15])[CH2:9]1)#[CH:2]
Reactant: C#Cc1cn([C@H]2C[C@H](F)[C@@H](CO)O2)c(=O)[nH]c1=O
Reactant: CC(C)(C)C(=O)Cl
Solvent: c1ccncc1
Product: C#Cc1cn([C@H]2C[C@H](F)[C@@H](COC(=O)C(C)(C)C)O2)c(=O)[nH]c1=O
Reaction time: 1.5 h

Procedure:
To a stirred solution of 2',3'-dideoxy-5-ethynyl-3'-fluorouridine (0.106 g 0.4 mmol) in dry pyridine (5 ml) at 0° C. was added trimethylacetyl chloride (0.06 ml, 0.48 mmol) and stirring continued at 0° C. for 1.5 hours. After stirring at room temperature for 24 hours, a further aliquot of the acid chloride (0.03 ml, 0.24 mmol) was added and stirring maintained for a further 3 hours. After quenching with methanol (3 ml), the solvent was removed by evaporation under reduced pressure and co-evaporated with several portions of ethanol (2×30 ml) and the resulting oil was chromatrographed on a silica gel column eluting with 5% MeOH/CH2Cl2. The appropriate fractions were combined and evaporated to dryness and the residue was recrystallised twice from ethanol to give the chromatographically pure title product.
Reaction SMILES: [CH2:1]([C:8]1[N:9]=[N:10][C:11]([C:16]2[CH2:17][CH2:18][NH:19][CH2:20][CH:21]=2)=[C:12]([CH3:15])[C:13]=1[CH3:14])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Cl[C:23]1[CH:28]=[CH:27][C:26]([C:29]([F:32])([F:31])[F:30])=[CH:25][N:24]=1>O1CCOCC1>[CH2:1]([C:8]1[N:9]=[N:10][C:11]([C:16]2[CH2:17][CH2:18][N:19]([C:23]3[CH:28]=[CH:27][C:26]([C:29]([F:32])([F:31])[F:30])=[CH:25][N:24]=3)[CH2:20][CH:21]=2)=[C:12]([CH3:15])[C:13]=1[CH3:14])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: FC(F)(F)c1ccc(Cl)nc1
Reactant: Cc1c(Cc2ccccc2)nnc(C2=CCNCC2)c1C
Solvent: C1COCCO1
Product: Cc1c(Cc2ccccc2)nnc(C2=CCN(c3ccc(C(F)(F)F)cn3)CC2)c1C
Temperature: 160 °C
Yield: 44.4 %

Procedure:
To a solution of 3-benzyl-4,5-dimethyl-6-(1,2,3,6-tetrahydropyridin-4-yl)pyridazine (70 mg, 0.175 mmol) in 2 mL dioxane is added 2-chloro-5-(trifluoromethyl)pyridine (64 mg, 0.35 mmol) and TEA (0.122 mL, 0.88 mmol) in a microwave tube. The reaction mixture is heated at 160° C. for 40 min in a microwave reactor. The mixture is concentrated to afford a brown oil and purified by prep HPLC, eluting with 10%-100% acetonitrile:water (both mobile phases modified by 3% n-PrOH). Fractions containing the desired product are combined and freeze-dried to afford a white solid (33 mg, 42%).
Reaction SMILES: CC1(C)[O:6][C:5](=O)[C@H:4]([C@@H:8]([C:13]([N:15]2[CH2:20][CH2:19][N:18]([C:21]3[S:25][N:24]=[C:23]([C:26]4[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=4)[N:22]=3)[CH2:17][CH2:16]2)=[O:14])[CH2:9][CH:10]([CH3:12])[CH3:11])[O:3]1.[NH2:33][OH:34]>CC(O)C>[OH:34][NH:33][C:5](=[O:6])[C@@H:4]([OH:3])[C@@H:8]([C:13]([N:15]1[CH2:16][CH2:17][N:18]([C:21]2[S:25][N:24]=[C:23]([C:26]3[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=3)[N:22]=2)[CH2:19][CH2:20]1)=[O:14])[CH2:9][CH:10]([CH3:12])[CH3:11]
Reactant: CC(C)C[C@H](C(=O)N1CCN(c2nc(-c3ccccc3)ns2)CC1)[C@@H]1OC(C)(C)OC1=O
Reactant: NO
Solvent: CC(C)O
Product: CC(C)C[C@H](C(=O)N1CCN(c2nc(-c3ccccc3)ns2)CC1)[C@H](O)C(=O)NO
Temperature: 25 °C
Reaction time: 2 h
Yield: 109.3 %

Procedure:
To a solution of (5S)-2,2-dimethyl-5-((1S)-3-methyl-1-{[4-(3-phenyl-1,2,4-thiadiazol-5-yl)-1-piperazinyl]carbonyl}butyl)-1,3-dioxolan-4-one (9.0 mg; 0.019 mmol; 1.0 eq.) in iPrOH (0.20 mL) was added an aqueous solution of hydroxylamine (50%; 0.0029 mL; 0.098 mmol; 5.0 eq.) and the resulting reaction mixture was stirred at RT for 2 h. Evaporation of the solvents gave the title product (2) as a colorless oil (9 mg; 100%). M−(ESI): 432.1; M+(ESI): 434.3. HPLC (Condition A): Rt: 3.1 min (HPLC purity: 79.3%).
Reaction SMILES: [F:1][C:2]([F:11])([CH:5]([F:10])[C:6]([F:9])([F:8])[F:7])[CH2:3][OH:4].[Br:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][C:23](O)=[O:24]>CS(O)(=O)=O.C1C=CC=CC=1>[Br:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][C:23]([O:4][CH2:3][C:2]([F:11])([F:1])[CH:5]([F:10])[C:6]([F:9])([F:7])[F:8])=[O:24]
Reactant: O=C(O)CCCCCCCCCCBr
Reactant: OCC(F)(F)C(F)C(F)(F)F
Agent: CS(=O)(=O)O
Solvent: c1ccccc1
Product: O=C(CCCCCCCCCCBr)OCC(F)(F)C(F)C(F)(F)F

Procedure:
The process of producing the surfactant of claim 1 comprising (a) reacting at reflux 2,2,3,4,4,4-hexafluorobutanol and 11-bromoundecanoic acid in presence of methane sulfonic acid as a catalyst and benzene as a solvent to obtain 2,2,3,4,4,4-hexafluorobutyl 11-bromoundecylate and then (b) reacting at reflux 2,2,3,4,4,4-hexafluorobutyl 11-bromoundecylate with pyridine in presence of methanol as a solvent to obtain 2,2,3,4,4,4-hexafluorobutyl 11-pyridylundecylate bromide.
Reaction SMILES: [O:1]([CH2:9][CH2:10][CH:11]1[C:16](=[O:17])[NH:15][C:14]2[CH:18]=[CH:19][CH:20]=[CH:21][C:13]=2[O:12]1)[Si](C(C)(C)C)(C)C.[CH2:22](Cl)[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1.[K+].[Br-]>>[CH2:22]([N:15]1[C:14]2[CH:18]=[CH:19][CH:20]=[CH:21][C:13]=2[O:12][CH:11]([CH2:10][CH2:9][OH:1])[C:16]1=[O:17])[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1
Reactant: CC(C)(C)[Si](C)(C)OCCC1Oc2ccccc2NC1=O
Reactant: ClCc1ccccc1
Agent: [Br-]
Agent: [K+]
Product: O=C1C(CCO)Oc2ccccc2N1Cc1ccccc1

Procedure:
Prepared from 2-(2-tert-butyldimethylsiloxyethyl)-3,4-dihydro-3-oxo-2H-1,4-benzoxazine by Methods F and G, alkylating with benzyl chloride, in 49% overall yield and crystallized from ether/hexane to produce a white solid, mp 83°-85.5° C.; IR (KBr) 3213, 1680, 1505, 1399, 1250, 1050, 753 cm-1 ; 1H NMR (CDCl3) δ2.17-2.38 (m, 3H), 3.92 (q, J=5.7 Hz, 2H), 4.84 (dd, J=7.5, 5.6 Hz, 1H), 5.16 (s, 2H), 6.86-7.03 (m, 4H), 7.21-7.37 (m, 5H); MH+ at m/z=284; Anal. Calc'd for C17H17NO3 : C, 72.07; H, 6.05; N, 4.94. Found: C, 72.08; H, 6.20; N, 4.87.
Reaction SMILES: [Cl:1][C:2]1[CH:10]=[CH:9][C:8]([CH3:11])=[CH:7][C:3]=1[C:4](Cl)=[O:5].[Cl-:12].[Al+3].[Cl-].[Cl-]>ClC1C=CC=CC=1>[Cl:12][C:2]1[CH:10]=[CH:9][C:8]([C:4]([C:3]2[CH:7]=[C:8]([CH3:11])[CH:9]=[CH:10][C:2]=2[Cl:1])=[O:5])=[CH:7][CH:3]=1
Reactant: [Cl-]
Reactant: Cc1ccc(Cl)c(C(=O)Cl)c1
Agent: [Al+3]
Solvent: Clc1ccccc1
Product: Cc1ccc(Cl)c(C(=O)c2ccc(Cl)cc2)c1
Temperature: 80 °C
Reaction time: 15 h
Yield: 157.5 %

Procedure:
A stirred solution of 2-chloro-5-methylbenzoyl chloride (9.41 g, 49.8 mmol) in chlorobenzene (14 ml) at 80° C. was treated with aluminum chloride (7.32 g, 54.9 mmol) in portions over 15 minutes. The mixture was stirred 15 hours at 80° C., cooled, quenched by addition of ice and concentrated hydrochloric acid (5.0 ml) and extracted with diethyl ether (2×50 ml). The combined extracts were washed with water, dried over anhydrous magnesium sulfate, and evaporated under vacuum. The residue was crystallized from n-hexane to provide 10.4 g (79%) of 3-(4-chlorobenzoyl)-4-chlorotoluene, m.p. 85°-90° C. Recrystallization raised the melting point to 90°-92° C.
Reaction SMILES: C(=O)([O-])[O-].[Na+].[Na+].[C:7]1(B(O)O)[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1.C([N:19]1[C:27]2[C:22](=[CH:23][CH:24]=[CH:25][CH:26]=2)[C:21]([C:28]2[N:32](C(=O)C)[C:31]3[CH:36]=[CH:37][C:38](Br)=[CH:39][C:30]=3[N:29]=2)=[N:20]1)(=O)C>O1CCCC1.C(OCC)(=O)C>[C:7]1([C:37]2[CH:38]=[CH:39][C:30]3[N:29]=[C:28]([C:21]4[NH:20][N:19]=[C:27]5[C:22]=4[CH:23]=[CH:24][CH:25]=[CH:26]5)[NH:32][C:31]=3[CH:36]=2)[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1
Reactant: OB(O)c1ccccc1
Reactant: CC(=O)n1nc(-c2nc3cc(Br)ccc3n2C(C)=O)c2ccccc21
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: CCOC(C)=O
Solvent: C1CCOC1
Product: c1ccc(-c2ccc3nc(-c4[nH]nc5ccccc45)[nH]c3c2)cc1
Temperature: 25 °C
Yield: 122.9 %

Procedure:
40 mg of sodium carbonate, 7 mg of dihydrogendichlorobis(di-tert-butylphosphonite-κP)palladate(2-) (POPd[0]) and 46 mg of phenylboronic acid are added under an argon atmosphere to a solution of 50 mg of 1-[2-(1-acetyl-1H-indazol-3-yl)-5-bromobenzimidazol-1-yl]ethanone in 800 μl of anhydrous tetrahydrofuran. The reaction mixture is brought to reflux for 3 hours and then cooled to ambient temperature. The mixture is then diluted with 3 ml of ethyl acetate and then washed with 2 times 2 ml of water. The organic phase is dried over magnesium sulphate and then concentrated to dryness under reduced pressure. 48 mg of a brown solid are obtained, which solid is dissolved in 500 μl of tetrahydrofuran, to which 500 μl of diethylamine are added. The reaction mixture is heated at 60° C. for 4 hours and then allowed to return to ambient temperature. The mixture is then concentrated to dryness and then the brown solid obtained is purified by LC-MS to produce 12.5 mg of 3-(6-phenyl-1H-benzimidazol-2-yl)-2H-indazole (6); analytical retention time 3.10, MS 311 [M+H]+.
Reaction SMILES: [OH:1][C:2]1[CH:15]=[CH:14][C:5]([C:6]([C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=2)=[O:7])=[CH:4][CH:3]=1.[C:16](Cl)(=[O:20])[C:17]([CH3:19])=[CH2:18].C(N(CC)CC)C>C(Cl)Cl>[C:16]([O:1][C:2]1[CH:3]=[CH:4][C:5]([C:6](=[O:7])[C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=2)=[CH:14][CH:15]=1)(=[O:20])[C:17]([CH3:19])=[CH2:18]
Reactant: O=C(c1ccccc1)c1ccc(O)cc1
Reactant: C=C(C)C(=O)Cl
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: C=C(C)C(=O)Oc1ccc(C(=O)c2ccccc2)cc1
Temperature: 0 °C
Reaction time: 0.5 h
Yield: 93 %

Procedure:
To a 100 mL round-bottomed flask equipped with a magnetic stirrer bar and an addition funnel was added 4-hydroxybenzophenone (1 g, 5.04 mmol) and CH2Cl2 (35 mL). The mixture was cooled to 0° C. and methacryloyl chloride (0.39 mL, 4.04 mmol) was added in one portion. After 30 minutes, triethylamine (0.7 mL, 5.04 mmol) dissolved in CH2Cl2 (10 mL) was added dropwise over 30 minutes. The reaction mixture was allowed to stir for a further 1 hour at 0° C. and then at room temperature for 3 hours. After this time, the organic mixture was washed with 0.1% NaOH (3×100 mL) and water (5×100 mL). The combined organic layers were dried over MgSO4 and then concentrated in vacuo to afford a crude product. The crude product was purified by column chromatography (100% CH2Cl2) to provide the compound as a white solid (yield=75%, 1 g).
Reaction SMILES: [C:1]([C:9]1[CH:10]=[C:11]([CH2:15][CH2:16][C:17]([OH:19])=O)[CH:12]=[CH:13][CH:14]=1)(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.S(Cl)([Cl:22])=O>>[C:1]([C:9]1[CH:10]=[C:11]([CH2:15][CH2:16][C:17]([Cl:22])=[O:19])[CH:12]=[CH:13][CH:14]=1)(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: O=C(O)CCc1cccc(C(=O)c2ccccc2)c1
Reactant: O=S(Cl)Cl
Product: O=C(Cl)CCc1cccc(C(=O)c2ccccc2)c1

Procedure:
A mixture of 18.15 g of 3-(m-benzoyl-phenyl)-propionic acid and 25 ml of thionyl chloride was refluxed for 11/2 hours and excess thionyl chloride was removed under reduced pressure to obtain 3-(m-benzoyl-phenyl)-propionyl chloride which was used as is for the next step.
Reaction SMILES: [C:1]([O:4][C@@H:5]1[CH:11]=[CH:10][C@H:9]([N:12]=[N+]=[N-])[C:6]21[CH2:8][CH2:7]2)(=[O:3])[CH3:2].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>O1CCCC1.O>[C:1]([O:4][C@@H:5]1[CH:11]=[CH:10][C@H:9]([NH2:12])[C:6]21[CH2:7][CH2:8]2)(=[O:3])[CH3:2]
Reactant: CC(=O)O[C@@H]1C=C[C@H](N=[N+]=[N-])C12CC2
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: C1CCOC1
Solvent: O
Product: CC(=O)O[C@@H]1C=C[C@H](N)C12CC2

Procedure:
A solution of the product of step b) (0.85 g) and triphenylphosphine (1.46 g) in tetrahydrofuran (5 ml) and water (1 ml) was stirred at ambient temperature under nitrogen for 64 hours. The reaction mixture was concentrated to dryness under reduced pressure azeotroping with toluene (2×50 ml) and purified by chromatography (SiO2; 97:2:1 ethyl acetate:methanol:ammonia) to afford the subtitle compound (0.67 g).