Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [NH2:1][C:2]1[CH:17]=[CH:16][C:5]([C:6]([NH:8][CH2:9][CH2:10][N:11]([CH2:14][CH3:15])[CH2:12][CH3:13])=[O:7])=[C:4]([O:18][CH3:19])[CH:3]=1.C(N(CC)CC)C.[CH3:27][S:28](Cl)(=[O:30])=[O:29].C(=O)(O)[O-].[Na+]>C(Cl)Cl>[CH2:14]([N:11]([CH2:12][CH3:13])[CH2:10][CH2:9][NH:8][C:6](=[O:7])[C:5]1[CH:16]=[CH:17][C:2]([N:1]([S:28]([CH3:27])(=[O:30])=[O:29])[S:28]([CH3:27])(=[O:30])=[O:29])=[CH:3][C:4]=1[O:18][CH3:19])[CH3:15]
Reactant: CCN(CC)CCNC(=O)c1ccc(N)cc1OC
Reactant: CS(=O)(=O)Cl
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: CCN(CC)CCNC(=O)c1ccc(N(S(C)(=O)=O)S(C)(=O)=O)cc1OC
Temperature: 25 °C
Reaction time: 2 h
Yield: 100.1 %

Procedure:
265 mg (1 mmol) of 4-amino-N-(2-diethylamino-ethyl)-2-methoxy-benzamide is introduced into 15 ml of methylene chloride and mixed in succession with 111 mg (1.1 mmol) of triethylamine and 126 mg (1.1 mmol) of methanesulfonic acid chloride. It is stirred for 2 hours at room temperature and then allowed to stand overnight. It is then mixed with 25 ml of saturated sodium bicarbonate solution and shaken out three times with 25 ml each of methylene chloride. The collected organic phase is dried, filtered and concentrated by evaporation. The residue is chromatographed on 10 g of basic silica gel (Isolute flash Si NH2) with a gradient from cyclohexane:ethyl acetate=100:0 to 50:50. 232 mg (52.6% of theory) of N-(2-diethylamino-ethyl)-4-(bismethanesulfonylamino)-2-methoxy-benzamide with a melting point of 144.1° C. is obtained.
Reaction SMILES: [NH2:1][C:2]1[C:3]2[C:10](I)=[CH:9][N:8]([C@@H:12]3[CH2:16][CH2:15][N:14]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[CH2:13]3)[C:4]=2[N:5]=[CH:6][N:7]=1.[O:24]([C:31]1[CH:36]=[CH:35][C:34](B(O)O)=[CH:33][CH:32]=1)[C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1.C([O-])([O-])=O.[Na+].[Na+]>COCCOC.O.C(Cl)Cl.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[C:20]([O:19][C:17]([N:14]1[CH2:15][CH2:16][C@@H:12]([N:8]2[C:4]3[N:5]=[CH:6][N:7]=[C:2]([NH2:1])[C:3]=3[C:10]([C:34]3[CH:35]=[CH:36][C:31]([O:24][C:25]4[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=4)=[CH:32][CH:33]=3)=[CH:9]2)[CH2:13]1)=[O:18])([CH3:23])([CH3:22])[CH3:21]
Reactant: CC(C)(C)OC(=O)N1CC[C@@H](n2cc(I)c3c(N)ncnc32)C1
Reactant: OB(O)c1ccc(Oc2ccccc2)cc1
Agent: Cl[Pd]Cl
Agent: [Fe+2]
Agent: O=C([O-])[O-]
Solvent: O
Solvent: COCCOC
Solvent: ClCCl
Product: CC(C)(C)OC(=O)N1CC[C@@H](n2cc(-c3ccc(Oc4ccccc4)cc3)c3c(N)ncnc32)C1
Temperature: 90 °C
Yield: 59.2 %

Procedure:
A mixture of (R)-tert-butyl 3-(4-amino-5-iodo-7H-pyrrolo[2,3-d]pyrimidin-7-yl)pyrrolidine-1-carboxylate (1) (2.0 g, 4.66 mmol), 4-phenoxyphenylboronic acid (1.3 g, 6.06 mmol), Pd(dppf)Cl2 (190 mg, 0.23 mmol) and Na2CO3 (1.9 g, 14.0 mmol) in DME (35.0 mL) and H2O (15.0 mL) was heated at 90° C. under N2 atmosphere overnight. After cooled down to r. t., the reaction mixture was diluted with water (50.0 mL) and DCM (50.0 mL). The layers were separated and the aqueous phase was extracted with DCM (25 mL×1). Combined organic phases were washed with brine, dried over Na2SO4 and concentrated under reduced pressure to obtain the crude product which was purified by column chromatographic (silica gel, 0-80% ethyl acetate in petroleum ether (“PE”) with DCM (1:1)) to afford (R)-tert-butyl-3-(4-amino-5-(4-phenoxyphenyl)-7H-pyrrolo[2,3-d]pyrimidin-7-yl)pyrrolidine-1-carboxylate (2) (1.3 g, 60% yield) as a yellow solid. LC-MS (ESI): (M+1) 472.1.
Reaction SMILES: C[N:2](C)[CH:3]=[C:4]([C:7]1[CH:12]=[C:11]([CH3:13])[N:10]=[C:9]([CH3:14])[CH:8]=1)[C:5]#[N:6].O.[NH2:17]N>C(O)C>[CH3:13][C:11]1[CH:12]=[C:7]([C:4]2[CH:5]=[N:6][NH:2][C:3]=2[NH2:17])[CH:8]=[C:9]([CH3:14])[N:10]=1
Reactant: Cc1cc(C(C#N)=CN(C)C)cc(C)n1
Reactant: NN
Solvent: O
Solvent: CCO
Product: Cc1cc(-c2cn[nH]c2N)cc(C)n1
Yield: 39 %

Procedure:
To stirred solution of 3-dimethylamino-2-(2,6-dimethyl-pyridin-4-yl)-acrylonitrile (2.2 g, 10.9 mmol) in ethanol (22 ml) was added at room temperature hydrazine monohydrate (1.17 ml, 24.1 mmol), the reaction mixture was heated under reflux conditions for 23 h and evaporated. Purification by column chromatography on silica gel (dichloromethane/methanol/NH4OH 80:10:1) and crystallization from diethyl ether yielded 4-(2,6-dimethyl-pyridin-4-yl)-2H-pyrazol-3-ylamine (0.8 g, 39%) as a light brown solid. MS (ISP) 189.3 [(M+H)+]; mp 222° C.
Reaction SMILES: [CH2:1]([O:3][C:4](=[O:28])[C:5]([C:24]([F:27])([F:26])[F:25])([O:19][Si](C)(C)C)[CH2:6][C:7]([C:10]1[CH:15]=[CH:14][C:13]([Cl:16])=[C:12]([O:17][CH3:18])[CH:11]=1)([CH3:9])[CH3:8])[CH3:2].O.O.O.[F-].C([N+](CCCC)(CCCC)CCCC)CCC.O>O1CCCC1>[CH2:1]([O:3][C:4](=[O:28])[C:5]([C:24]([F:25])([F:27])[F:26])([OH:19])[CH2:6][C:7]([C:10]1[CH:15]=[CH:14][C:13]([Cl:16])=[C:12]([O:17][CH3:18])[CH:11]=1)([CH3:9])[CH3:8])[CH3:2]
Reactant: CCOC(=O)C(CC(C)(C)c1ccc(Cl)c(OC)c1)(O[Si](C)(C)C)C(F)(F)F
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: [F-]
Solvent: O
Solvent: C1CCOC1
Product: CCOC(=O)C(O)(CC(C)(C)c1ccc(Cl)c(OC)c1)C(F)(F)F
Temperature: 25 °C
Reaction time: 1 h
Yield: 54.2 %

Procedure:
8.9 g (20.18 mmol) of contaminated ethyl-4-(4-chloro-3-methoxyphenyl)-4-methyl-2-(trifluoromethyl)-2-(trimethylsilyloxy)-pentanoate is dissolved in 116 ml of tetrahydrofuran and mixed at room temperature with 6.37 g (20.18 mmol) of tetrabutylammonium fluoride trihydrate and stirred for one hour at room temperature. The reaction mixture is mixed with water and extracted twice with 250 ml each of diethyl ether. The combined organic extracts are washed with water and with brine. After drying on sodium sulfate, the dessicant is filtered off, the solvent is spun off, and the remaining residue is chromatographed on silica gel (mobile solvent: ethyl acetate/hexane). 4.03 g (54.2%) of the desired compound is isolated. Other batches are implemented analogously.
Reaction SMILES: S(Cl)(Cl)=O.CC(CCCC)C(O)=O.CC(CCCC)C(Cl)=O.[CH3:23][CH:24]([CH2:30][CH2:31][CH2:32][CH3:33])[C:25]([N:27]=[C:28]=[S:29])=[O:26].[CH3:34][O:35][C:36]1[CH:37]=[C:38]2[C:43](=[CH:44][C:45]=1[O:46][CH3:47])[N:42]=[CH:41][CH:40]=[C:39]2[O:48][C:49]1[CH:55]=[CH:54][C:52]([NH2:53])=[CH:51][CH:50]=1>C(O)C.C1(C)C=CC=CC=1>[CH3:34][O:35][C:36]1[CH:37]=[C:38]2[C:43](=[CH:44][C:45]=1[O:46][CH3:47])[N:42]=[CH:41][CH:40]=[C:39]2[O:48][C:49]1[CH:50]=[CH:51][C:52]([NH:53][C:28]([NH:27][C:25](=[O:26])[CH:24]([CH3:23])[CH2:30][CH2:31][CH2:32][CH3:33])=[S:29])=[CH:54][CH:55]=1
Reactant: CCCCC(C)C(=O)N=C=S
Reactant: COc1cc2nccc(Oc3ccc(N)cc3)c2cc1OC
Agent: CCCCC(C)C(=O)Cl
Agent: CCCCC(C)C(=O)O
Solvent: Cc1ccccc1
Solvent: O=S(Cl)Cl
Solvent: CCO
Product: CCCCC(C)C(=O)NC(=S)Nc1ccc(Oc2ccnc3cc(OC)c(OC)cc23)cc1
Temperature: 100 °C
Reaction time: 2 h
Yield: 68 %

Procedure:
Toluene (20 ml) and thionyl chloride (1 ml) were added to commercially available 2-methylhexanoic acid (80 mg), and the mixture was heated at 100° C. for one hr. The solvent was removed by distillation, and 2-methylhexanoyl isothiocyanate was prepared using the resultant 2-methylhexanoyl chloride as a starting compound according to the description of the literature. 2-Methylhexanoyl isothiocyanate was dissolved in ethanol (1 ml) to prepare a solution. 4-[(6,7-Dimethoxy-4-quinolyl)oxy]aniline (50 mg), toluene (5 ml), and ethanol (1 ml) were added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (54 mg, yield 68%).
Reaction SMILES: [OH-].[Na+].[N+:3]([C:6]1[C:7]([NH:12][C:13]2[CH:14]=[C:15]([CH:21]=[CH:22][CH:23]=2)[C:16]([O:18]CC)=[O:17])=[N:8][CH:9]=[CH:10][CH:11]=1)([O-:5])=[O:4].Cl>C(O)C.O1CCOCC1>[N+:3]([C:6]1[C:7]([NH:12][C:13]2[CH:14]=[C:15]([CH:21]=[CH:22][CH:23]=2)[C:16]([OH:18])=[O:17])=[N:8][CH:9]=[CH:10][CH:11]=1)([O-:5])=[O:4]
Reactant: CCOC(=O)c1cccc(Nc2ncccc2[N+](=O)[O-])c1
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: C1COCCO1
Solvent: CCO
Product: O=C(O)c1cccc(Nc2ncccc2[N+](=O)[O-])c1
Temperature: 25 °C
Reaction time: 1 h
Yield: 90.5 %

Procedure:
4N Aqueous solution of sodium hydroxide (1 ml) was added to a solution of ethyl 3-[(3-nitropyridin-2-yl)amino]benzoate (322 mg) in ethanol (2 ml) and 1,4-dioxane (2 ml). After stirred at room temperature for 1 hour, the mixture was acidified with dilute hydrochloric acid and extracted with ethyl acetate. The organic phase was washed with water and brine, dried over magnesium sulfate and concentrated to give 3-[(3-nitropyridin-2-yl)amino]benzoic acid (263 mg) as solid.
Reaction SMILES: C(=O)(O[C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1)OC.[C:12](=O)([O:20]C1C=CC=CC=1)[O:13][C:14]1C=CC=CC=1>>[C:12]([O:13][CH3:14])(=[O:20])[C:5]1[CH:6]=[CH:7][CH:8]=[CH:9][CH:10]=1
Reactant: COC(=O)Oc1ccccc1
Reactant: O=C(Oc1ccccc1)Oc1ccccc1
Product: COC(=O)c1ccccc1
Yield: 45 %

Procedure:
Into an autoclave made of SUS316 having an internal volume of 100 ml were charged phenyl benzoate 30 g (151 mmole) produced above, dimethyl carbonate 6.82 g (75.7 mmole) and gallium triisopropoxide 0.38 g (1.51 mmole). The pressure was elevated to 20 kg/cm2 with nitrogen, and the contents were then reacted for two hours at 150° C. After completing the reaction, the reaction mixture was analyzed by gas chromatography. As a result, the yield of methyl phenyl carbonate was 25%, and the yield of diphenyl carbonate was 20%. Furthermore, methyl benzoate was produced as a by-product with a yield of 45% (the yield is given in terms of phenyl benzoate).
Reaction SMILES: [CH2:1]([O:3][C:4]([C:6](=[C:15]([C:20](=[O:53])[N:21]([CH:33]([CH3:52])[CH:34]([CH2:50][OH:51])[CH2:35][C:36]1[O:37][C:38]([C:41](=[O:49])[NH:42][C:43]2[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=2)=[CH:39][CH:40]=1)[CH2:22][C:23]1[CH:32]=[CH:31][C:30]2[C:25](=[CH:26][CH:27]=[CH:28][CH:29]=2)[CH:24]=1)[O:16][CH2:17][O:18][CH3:19])[CH2:7][C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])=[O:5])[CH3:2].CC(OI1(OC(C)=O)(OC(C)=O)OC(=O)C2C=CC=CC1=2)=O.C(=O)([O-])O.[Na+].S([O-])([O-])(=O)=S.[Na+].[Na+]>C(Cl)(Cl)Cl>[CH2:1]([O:3][C:4]([C:6](=[C:15]([C:20](=[O:53])[N:21]([CH:33]([CH3:52])[CH:34]([CH:50]=[O:51])[CH2:35][C:36]1[O:37][C:38]([C:41](=[O:49])[NH:42][C:43]2[CH:44]=[CH:45][CH:46]=[CH:47][CH:48]=2)=[CH:39][CH:40]=1)[CH2:22][C:23]1[CH:32]=[CH:31][C:30]2[C:25](=[CH:26][CH:27]=[CH:28][CH:29]=2)[CH:24]=1)[O:16][CH2:17][O:18][CH3:19])[CH2:7][C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])=[O:5])[CH3:2]
Reactant: CCOC(=O)C(CC(=O)OC(C)(C)C)=C(OCOC)C(=O)N(Cc1ccc2ccccc2c1)C(C)C(CO)Cc1ccc(C(=O)Nc2ccccc2)o1
Agent: CC(=O)OI1(OC(C)=O)(OC(C)=O)OC(=O)c2ccccc21
Agent: O=C([O-])O
Agent: O=S([O-])([O-])=S
Solvent: ClC(Cl)Cl
Product: CCOC(=O)C(CC(=O)OC(C)(C)C)=C(OCOC)C(=O)N(Cc1ccc2ccccc2c1)C(C)C(C=O)Cc1ccc(C(=O)Nc2ccccc2)o1
Yield: 52.6 %

Procedure:
124 mg of tert-butyl 3-(ethoxycarbonyl)-4-[N-[(1RS,2RS)-2-(hydroxymethyl)-1-methyl-3-{5-(phenylcarbamoyl)-2-furyl}propyl]-N-(2-naphthylmethyl)carbamoyl]-4-(methoxymethyloxy)-3-butenoate was dissolved in 3 ml of chloroform and stirred with 288 mg of the Dess-Martin reagent (periodinane) at room temperature for 30 minutes. The reaction solution was poured into a mixture of saturated aqueous sodium hydrogencarbonate and saturated aqueous sodium thiosulfate and extracted with ethyl acetate. The organic layer was washed with saturated aqueous sodium chloride and dried over anhydrous magnesium sulfate. The desiccant was filtered off, and the solvent was distilled off under reduced pressure. The residue was purified by silica gel thin layer chromatography [Kieselgel™ 60F254, Art™5744; hexane/ethyl acetate=1/2] to give 65 mg (yield: 53%) of the title compound as a white solid.
Reaction SMILES: [NH2:1][C:2]1[CH:9]=[CH:8][C:5]([C:6]#[N:7])=[CH:4][CH:3]=1.[Cl:10]N1C(=O)CCC1=O>CC#N>[NH2:1][C:2]1[CH:9]=[CH:8][C:5]([C:6]#[N:7])=[CH:4][C:3]=1[Cl:10]
Reactant: O=C1CCC(=O)N1Cl
Reactant: N#Cc1ccc(N)cc1
Solvent: CC#N
Product: N#Cc1ccc(N)c(Cl)c1
Temperature: 90 °C
Reaction time: 2 h
Yield: 94.4 %

Procedure:
To a stirred solution of 4-aminobenzonitrile (10.0 g, 84.7 mmol) in MeCN (100 mL) at 90° C. was slowly added N-chlorosuccinimide (12.4 g, 93 mmol). After the addition of N-chlorosuccinimide, the reaction mixture was stirred at 90° C. for 2 h. The reaction mixture was then cooled to rt and concentrated under reduced pressure. The residue was dissolved in 500 mL of CH2Cl2 and washed with 5% aq NaOH. The organic layer was dried over MgSO4 and concentrated under reduced pressure to give 4-amino-3-chlorobenzonitrile as a tan solid (12.2 g, 95%). 1H NMR (300 MHz, CDCl3) δ 7.54 (d, J=1.7 Hz, 1H), 7.35 (dd, J=1.8, 8.4 Hz, 1H), 6.77 (d, J=8.5 Hz, 1H), 4.63 (br s, 2H).
Reaction SMILES: [C:1]1([N:7]2[CH2:12][CH2:11][NH:10][CH2:9][CH2:8]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[C:13]1([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)[CH:18]=[CH:17][CH:16]=[C:15]([CH:19]=O)[CH:14]=1.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+].C1(C2C=CC=CC=2)C=CC=CC=1CN1CCN(C2C=CC=CC=2)CC1>>[C:13]1([C:21]2[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=2)[CH:18]=[CH:17][CH:16]=[C:15]([CH2:19][N:10]2[CH2:11][CH2:12][N:7]([C:1]3[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=3)[CH2:8][CH2:9]2)[CH:14]=1
Reactant: c1ccc(N2CCNCC2)cc1
Reactant: O=Cc1cccc(-c2ccccc2)c1
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: [Na+]
Agent: c1ccc(-c2ccccc2CN2CCN(c3ccccc3)CC2)cc1
Product: c1ccc(-c2cccc(CN3CCN(c4ccccc4)CC3)c2)cc1

Procedure:
48.6 mg of the target compound (0.15 mmol, 18.3%) was obtained using 1-phenylpiperazine (266 mg, 1.64 mmol), biphenyl-3-carbaldehyde (150 mg, 0.82 mmol) and NaBH(OAc)3 (529 mg, 2.46 mmol) according to the synthesis method of Compound 1.
Reaction SMILES: [C:1]([OH:12])(=O)/[CH:2]=[CH:3]/[CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH3:10].[CH2:13]([N:15]([CH2:20][CH3:21])[CH2:16][CH2:17][CH2:18][NH2:19])[CH3:14]>>[CH2:13]([N:15]([CH2:20][CH3:21])[CH2:16][CH2:17][CH2:18][NH:19][C:1](=[O:12])/[CH:2]=[CH:3]/[CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH3:10])[CH3:14]
Reactant: CCCCCCC/C=C/C(=O)O
Reactant: CCN(CC)CCCN
Product: CCCCCCC/C=C/C(=O)NCCCN(CC)CC

Procedure:
The same operation as in Example 1-1 or 1-2 was carried out using trans-2-decenoic acid and N,N-diethylpropane-1,3-diamine as starting materials to give the aimed compound.
Reaction SMILES: [CH:1]1([CH2:6][CH:7]([N:11]2[C:16](=[O:17])[CH:15]=[C:14]([O:18][C:19]3[CH:24]=[CH:23][C:22]([O:25][CH3:26])=[CH:21][CH:20]=3)[CH:13]=[N:12]2)[C:8](O)=[O:9])[CH2:5][CH2:4][CH2:3][CH2:2]1.[NH2:27][C:28]1[CH:32]=[CH:31][N:30]([CH2:33][C:34]([CH3:37])([OH:36])[CH3:35])[N:29]=1>>[CH:1]1([CH2:6][CH:7]([N:11]2[C:16](=[O:17])[CH:15]=[C:14]([O:18][C:19]3[CH:24]=[CH:23][C:22]([O:25][CH3:26])=[CH:21][CH:20]=3)[CH:13]=[N:12]2)[C:8]([NH:27][C:28]2[CH:32]=[CH:31][N:30]([CH2:33][C:34]([OH:36])([CH3:35])[CH3:37])[N:29]=2)=[O:9])[CH2:5][CH2:4][CH2:3][CH2:2]1
Reactant: COc1ccc(Oc2cnn(C(CC3CCCC3)C(=O)O)c(=O)c2)cc1
Reactant: CC(C)(O)Cn1ccc(N)n1
Product: COc1ccc(Oc2cnn(C(CC3CCCC3)C(=O)Nc3ccn(CC(C)(C)O)n3)c(=O)c2)cc1
Yield: 26 %

Procedure:
Using the method described in Example 11, 3-cyclopentyl-2-[4-(4-methoxy-phenoxy)-6-oxo-6H-pyridazin-1-yl]-propionic acid (Intermediate 26) and 1-(3-amino-pyrazol-1-yl)-2-methyl-propan-2-ol (Intermediate 1) afforded 3-cyclopentyl-N-[1-(2-hydroxy-2-methyl-propyl)-1H-pyrazol-3-yl]-2-[4-(4-methoxy-phenoxy)-6-oxo-6H-pyridazin-1-yl]-propionamide as a white solid (40.3 mg, 26%); ES+-HRMS m/e calcd for C26H33N5O5 [M+H+] 496.2555 found 496.2554. 1H-NMR (400 MHz, DMSO-d6) δ ppm 1.05 (s, 3H), 1.06 (s, 3H), 1.09 (m, 1H), 1.19-1.78 (m, 8H), 1.91 (m, 1H), 2.28 (m, 1H), 3.79 (s, 3H), 3.89 (s, 2H), 4.67 (s, 1H), 5.46 (dd, J=4.0, J=11.1 Hz, 1H), 5.67 (d, J=2.8 Hz, 1H), 6.39 (d, J=2.3 Hz, 1H), 7.05 (d, J=9.1 Hz, 2H), 7.23 (d, J=9.1 Hz, 2H), 7.52 (d, J=2.3 Hz, 1H), 8.10 (d, J=2.8 Hz, 1H), 10.79 (s, 1H).
Reaction SMILES: I[C:2]1[N:6]2[CH:7]=[CH:8][CH:9]=[CH:10][C:5]2=[N:4][C:3]=1[C:11]([O:13][CH2:14][CH3:15])=[O:12].[C:16]1([C:22]#[CH:23])[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1.C(N(CC)CC)C>CN(C)C=O.[Cu](I)I.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[C:16]1([C:22]#[C:23][C:2]2[N:6]3[CH:7]=[CH:8][CH:9]=[CH:10][C:5]3=[N:4][C:3]=2[C:11]([O:13][CH2:14][CH3:15])=[O:12])[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1
Reactant: CCOC(=O)c1nc2ccccn2c1I
Reactant: C#Cc1ccccc1
Agent: I[Cu]I
Agent: [Pd]
Agent: O=C(/C=C/c1ccccc1)/C=C/c1ccccc1
Solvent: CN(C)C=O
Solvent: CCN(CC)CC
Product: CCOC(=O)c1nc2ccccn2c1C#Cc1ccccc1
Temperature: 25 °C
Reaction time: 16 h
Yield: 76.4 %

Procedure:
In a flask placed under an argon flow, 1.82 g (5.77 mmol) of ethyl 3-iodoimidazo[1,2-a]pyridine-2-carboxylate were dissolved in 6 ml of dimethylformamide with magnetic stirring. To this solution were added: 0.11 g (0.577 mmol) of copper iodide, 0.776 ml (6.93 mmol) of phenylacetylene and 6 ml (43 mmol) of triethylamine. The reaction medium was degassed with argon for 10 min before adding 0.529 g (0.577 mmol) of Pd2(dba)3. The mixture was stirred at r.t. for 16 h before being filtered on celite. The celite was washed with 50 ml of ethyl acetate, and then the filtrate was washed with 2×50 ml of water. After separation, the aqueous phase was extracted with 2×50 ml of ethyl acetate; the combined organic phases were washed with 70 ml of a saturated NaCl aqueous solution, dried on Na2SO4 which was then removed by filtration. The obtained filtrate was concentrated in vacuo. The crude residue was purified by flash chromatography on a silica gel cartridge (eluent: heptane/ethyl acetate, 6/4, v/v). 1.28 g (yield=57%) of ethyl 3-(phenylethynyl)imidazo[1,2-a]pyridine-2-carboxylate were obtained as a pale yellow solid. LC-MS: m/z=291 (MH+); UV purity at 254 nm=93%. 1H NMR (300 MHz, DMSO) δ 8.70 (d, J=6.8 Hz, 1H), 7.74 (dd, J=22.1, 6.2 Hz, 3H), 7.53 (dd, J=17.6, 6.9 Hz, 4H), 7.23 (t, J=6.3 Hz, 1H), 4.36 (d, J=4.7 Hz, 2H), 1.36 (d, J=7.1 Hz, 3H).
Reaction SMILES: Br[C:2]1[S:6][C:5]([C:7]([NH:9][C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=2[Cl:16])=[O:8])=[CH:4][CH:3]=1.[Cl:17][C:18]1[C:19](B2OC(C)(C)C(C)(C)O2)=[CH:20][C:21]2[S:25][CH:24]=[N:23][C:22]=2[CH:26]=1.C(=O)([O-])[O-].[Na+].[Na+].CC(=O)OCC.[Cl-].[Na+].O>COCCOC.CCO.O.[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.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[Cl:16][C:11]1[CH:12]=[CH:13][CH:14]=[CH:15][C:10]=1[NH:9][C:7]([C:5]1[S:6][C:2]([C:19]2[C:18]([Cl:17])=[CH:26][C:22]3[N:23]=[CH:24][S:25][C:21]=3[CH:20]=2)=[CH:3][CH:4]=1)=[O:8]
Reactant: O=C(Nc1ccccc1Cl)c1ccc(Br)s1
Reactant: CC1(C)OB(c2cc3scnc3cc2Cl)OC1(C)C
Agent: [Pd]
Agent: O=C([O-])[O-]
Agent: [Cl-]
Solvent: O
Solvent: CCO
Solvent: COCCOC
Product: O=C(Nc1ccccc1Cl)c1ccc(-c2cc3scnc3cc2Cl)s1
Temperature: 110 °C
Yield: 67.4 %

Procedure:
A mixture of (5-bromo(2-thienyl))-N-(2-chlorophenyl)carboxamide (7, 19 mg, 0.06 mmol), 5-chloro-6-(4,4,5,5-tetramethyl(1,3,2-dioxaborolan-2-yl))benzothiazole (20) (17 mg, 0.06 mmol), tetrakis(triphenylphosphine)-palladium(0) (Pd(Ph3P)4, 7 mg) and sodium carbonate (19 mg) in 0.5 ml DME, 0.5 ml EtOH and 0.25 ml water was heated under Ar in microwave reactor at 110° C. for 30 min. The reaction mixture was worked up with EA/brine. Org. phase was concentrated and then subjected to silica gel flash chromatography (0-60% B; A: hexane; B: 50% EA in hexane) to furnish 16.4 mg of N-(2-chlorophenyl)[5-(5-chlorobenzothiazol-6-yl)(2-thienyl)]carboxamide (22) as off-white solid (yield: 67.4%; purity>95%). LC-MS: calcd. for C18H10Cl2N2OS2: 406 (M+1).
Reaction SMILES: [CH3:1][C:2]1[CH:18]=[CH:17][CH:16]=[C:15]([Cl:19])[C:3]=1[NH:4][C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][C:6]=1[CH2:11][C:12]([OH:14])=[O:13].O[CH2:21][C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][N:23]=1.C1(C)C=CC=CC=1>S(=O)(=O)(O)O.O>[N:23]1[CH:24]=[CH:25][CH:26]=[CH:27][C:22]=1[CH2:21][O:13][C:12](=[O:14])[CH2:11][C:6]1[CH:7]=[CH:8][CH:9]=[CH:10][C:5]=1[NH:4][C:3]1[C:15]([Cl:19])=[CH:16][CH:17]=[CH:18][C:2]=1[CH3:1]
Reactant: Cc1cccc(Cl)c1Nc1ccccc1CC(=O)O
Reactant: OCc1ccccn1
Agent: O=S(=O)(O)O
Solvent: Cc1ccccc1
Solvent: O
Product: Cc1cccc(Cl)c1Nc1ccccc1CC(=O)OCc1ccccn1
Temperature: 5 °C

Procedure:
A mixture of 1.0 g of [o-(2-methyl-6-chloro-anilino)-phenyl]-acetic acid, 15 ml of 2-hydroxymethyl-pyridine and 15 ml of anhydrous toluene is treated with 2 drops of concentrated sulphuric acid. The solution is heated to 130°C for 1 hour, during which the resulting water is distilled off azeotropically with the toluene. A further 20 ml of anhydrous toluene are added and again distilled off. The solution is then poured onto 150 g of ice. The mixture is twice extracted with 50 ml of ether at a time. The combined ether extracts are shaken with 15 ml of 2 N-hydrochloric acid at 5°C. The hydrochloric acid solution is separated off and rendered alkaline with 2 N-sodium hydroxide solution at 5°C. The suspension is extracted with 50 ml of ether and the ether solution is separated off, washed with 10 ml of water, dried over magnesium sulphate and evaporated to dryness under 0.1 mm Hg at 40°C. The residue is crystallised from ether-petroleum ether. [o-(2-methyl-6-chloro-anilino)-phenyl]-acetic acid (2-pyridyl)-methyl ester melts at 80°-82°C.
Reaction SMILES: [Si:1]([O:8][CH2:9][C@H:10]1[C@@H:15]([OH:16])[CH:14]=[CH:13][CH2:12][O:11]1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].C1C=C(Cl)C=C(C(OO)=[O:25])C=1.CSC>C(Cl)Cl>[Si:1]([O:8][CH2:9][C@H:10]1[C@@H:15]([OH:16])[C@H:14]2[C@H:13]([O:25]2)[CH2:12][O:11]1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2]
Reactant: O=C(OO)c1cccc(Cl)c1
Reactant: CC(C)(C)[Si](C)(C)OC[C@@H]1OCC=C[C@@H]1O
Solvent: ClCCl
Solvent: CSC
Product: CC(C)(C)[Si](C)(C)OC[C@@H]1OC[C@H]2O[C@H]2[C@@H]1O
Temperature: 0 °C
Reaction time: 0.17 h

Procedure:
To a 0° C., stirred solution of cis-2-(tert-butyldimethylsilanyloxymethyl)-3,6-dihydro-2H-pyran-3-ol (0.200 g, 0.91 mmol) in CH2Cl2 (15 ml) was added m-CPBA (75%, 0.46 g, 2.68 mmol) and the mixture was stirred for 1 H at 0° C. Dimethyl sulfide (0.01 ml) was added and stirring was continued for 10 min. The solvent was removed in vacuo and the crude product was diluted with EtOAc (30 ml). The resulting solution was washed successively with saturated aqueous Na2CO3 (10 ml), water (10 ml×2) and brine (10 ml). The organic phase was dried over anhydrous Na2SO4. The solvent was removed in vacuo and the crude product was purified by flash chromatography (25-40% EtOAc in hexane).
Reaction SMILES: [C:1]([N:5]=[N:6][C:7]1([N:13]=[C:14]=[S:15])[CH2:12][CH2:11][CH2:10][CH2:9][CH2:8]1)([CH3:4])([CH3:3])[CH3:2].[CH2:16]([NH2:20])[CH:17]([CH3:19])[CH3:18].[N-]=C=S>CCCCC>[C:1]([N:5]=[N:6][C:7]1([NH:13][C:14]([NH:20][CH2:16][CH:17]([CH3:19])[CH3:18])=[S:15])[CH2:8][CH2:9][CH2:10][CH2:11][CH2:12]1)([CH3:4])([CH3:2])[CH3:3]
Reactant: CC(C)CN
Reactant: CC(C)(C)N=NC1(N=C=S)CCCCC1
Agent: [N-]=C=S
Solvent: CCCCC
Product: CC(C)CNC(=S)NC1(N=NC(C)(C)C)CCCCC1
Reaction time: 4 h

Procedure:
To 9.1 grams (.0394 moles) of 1-t-butylazo-1-isothiocyanatocyclohexane stirred with a magnetic stirrer in a 50 ml erlenmeyer flask was added 2.88 grams (.0394 moles) of isobutylamine at room temperature. The reaction mixture became viscous so pentane was added and the reaction was stirred an additional 4 hours and the pentane stripped off to leave a yellow solid weighing 11.6 grams (97% crude yield). The product melted at 90°-93° C. and the infrared spectrum of the product had a strong broad band at 1520-1550 cm-1 and a NH band at 3270 cm-1. There was only a trace of the isothiocyanate band at 2040 cm-1 which was present in the starting material.
Reaction SMILES: [CH3:1][C:2]1([CH3:20])[C:10]2[C:5](=[CH:6][CH:7]=[C:8](OS(C(F)(F)F)(=O)=O)[CH:9]=2)[C:4](=[O:19])[CH2:3]1.[CH3:21][N:22]([CH3:32])[C:23]1[CH:28]=[CH:27][C:26](B(O)O)=[CH:25][CH:24]=1>>[CH3:21][N:22]([CH3:32])[C:23]1[CH:28]=[CH:27][C:26]([C:8]2[CH:9]=[C:10]3[C:5](=[CH:6][CH:7]=2)[C:4](=[O:19])[CH2:3][C:2]3([CH3:20])[CH3:1])=[CH:25][CH:24]=1
Reactant: CC1(C)CC(=O)c2ccc(OS(=O)(=O)C(F)(F)F)cc21
Reactant: CN(C)c1ccc(B(O)O)cc1
Product: CN(C)c1ccc(-c2ccc3c(c2)C(C)(C)CC3=O)cc1

Procedure:
The title compound was prepared from trifluoro-methanesulfonic acid 3,3-dimethyl-1-oxo-indan-5-yl ester and 4-(dimethylamino)phenyl boronic acid according to the procedure described in example 21. MS m/z 280; HRMS: calcd for C19H21NO+H+, 280.16959; found (ESI, [M+H]+), 280.1691.