Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: Br[C:2]1[CH:7]=[CH:6][C:5]([CH2:8][O:9][Si:10]([C:13]([CH3:16])([CH3:15])[CH3:14])([CH3:12])[CH3:11])=[CH:4][N:3]=1.[O:17]1CCC[CH2:18]1.C([Li])CCC.CN(C)C=O>C(OCC)C>[Si:10]([O:9][CH2:8][C:5]1[CH:6]=[CH:7][C:2]([CH2:18][OH:17])=[N:3][CH:4]=1)([C:13]([CH3:16])([CH3:15])[CH3:14])([CH3:12])[CH3:11]
Reactant: C1CCOC1
Reactant: CC(C)(C)[Si](C)(C)OCc1ccc(Br)nc1
Agent: [Li]CCCC
Solvent: CCOCC
Solvent: CN(C)C=O
Product: CC(C)(C)[Si](C)(C)OCc1ccc(CO)nc1
Temperature: 25 °C
Reaction time: 1 h
Yield: 64 %

Procedure:
To a mixture of 2-bromo-5-({[tert-butyl(dimethyl)silyl]oxy}methyl)pyridine (11 g) and tetrahydrofuran (450 mL) was added n-butyllithium (1.6 M hexane solution, 25.3 mL) at −78° C., and the reaction mixture was stirred for 1 hr. Then, N,N-dimethylformamide (3.17 mL) was added at −78° C., and the temperature of the mixture was raised to room temperature and stirred for 16 hr. The reaction mixture was diluted with diethyl ether, washed with saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure. The obtained residue was dissolved in methanol (200 mL), sodium borohydride (1.95 g) was added at 0° C., and the reaction mixture was stirred at room temperature for 2 hr. The solvent was evaporated under reduced pressure, and the obtained residue was extracted with saturated aqueous ammonium chloride solution and ethyl acetate. The ethyl acetate layer was washed with saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure and the residue was purified by silica gel column chromatography to give the title compound as colorless crystals (7.53 g, 64%).
Reaction SMILES: [CH:1]1([C:7]([OH:9])=O)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.C(Cl)CCl.[NH2:14][C:15]1[CH:20]=[CH:19][C:18]([N:21]2[C:25]([C:26]([F:29])([F:28])[F:27])=[CH:24][C:23]([C:30]([F:33])([F:32])[F:31])=[N:22]2)=[CH:17][CH:16]=1.CN(C1C=CC=CN=1)C>C(Cl)Cl>[F:33][C:30]([F:31])([F:32])[C:23]1[CH:24]=[C:25]([C:26]([F:27])([F:28])[F:29])[N:21]([C:18]2[CH:17]=[CH:16][C:15]([NH:14][C:7]([CH:1]3[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6]3)=[O:9])=[CH:20][CH:19]=2)[N:22]=1
Reactant: Nc1ccc(-n2nc(C(F)(F)F)cc2C(F)(F)F)cc1
Reactant: O=C(O)C1CCCCC1
Agent: CN(C)c1ccccn1
Solvent: ClCCl
Solvent: ClCCCl
Product: O=C(Nc1ccc(-n2nc(C(F)(F)F)cc2C(F)(F)F)cc1)C1CCCCC1
Reaction time: 0.25 h

Procedure:
A mixture of cyclohexanecarboxylic acid (0.10 g, 0.8 mmol) and EDC (0.077 g, 0.4 mmol) in CH2Cl2 (1.5 mL) was stirred for 15 minutes. 1(4′-Aminophenyl)-3,5-bis(trifluoromethyl)pyrazole (0.059 g, 0.2 mmol) was added followed by dimethylaminopyridine (0.01 g, 0.1 mmol). After 3 hours the mixture was diluted with CH2Cl2 (50 mL), washed with 10% NaHCO3 (2×50 mL), brine (3×25mL), and dried over anhydrous Na2SO4. Evaporation of the solvent gave the above-named compound as a solid that crystallized from benzene (0.075 g, 92%): mp 178-180° C.; 1H NMR (CDCl3) δ 1.35 (3H, m), 1.66 (2H, m), 1.75 (1H, m), 1.85 (2H, m), 2.0 (2H, m), 2.3 (1H, m), 7.08 (1H, s), 7.45 (1H, d, J=8.5 Hz), 7.75 (2H, d, J=8.5 Hz).
Reaction SMILES: Cl.CO.[OH:4][C:5]1[CH:15]=[CH:14][C:8]2[C:9](=[O:13])[CH:10]=[CH:11][O:12][C:7]=2[CH:6]=1.[CH2:16]([O:18][C:19]1[CH:20]=[C:21]([CH:24]=[CH:25][C:26]=1[O:27][CH2:28][CH3:29])[CH:22]=O)[CH3:17]>O>[CH2:16]([O:18][C:19]1[CH:20]=[C:21]([CH:22]=[C:10]2[C:9](=[O:13])[C:8]3[CH:14]=[CH:15][C:5]([OH:4])=[CH:6][C:7]=3[O:12][CH2:11]2)[CH:24]=[CH:25][C:26]=1[O:27][CH2:28][CH3:29])[CH3:17]
Reactant: O=c1ccoc2cc(O)ccc12
Reactant: CCOc1ccc(C=O)cc1OCC
Agent: Cl
Solvent: O
Solvent: CO
Product: CCOc1ccc(C=C2COc3cc(O)ccc3C2=O)cc1OCC
Reaction time: 72 h

Procedure:
After a saturated hydrogen chloride-methanol solution 20 ml was added to 7-hydroxy-4(4H)-benzopyranone 1.0 g and 3,4-diethoxybenzaldehyde 1.58 ml, the mixture was srtirred for 72 hours, water 100 ml was added, and the precipitated crystals were filtered. The crystals were added to methanol 60 ml of 55° C., and the mixture was stirred for 15 minutes and filtered. The resulting crystals were dried over phosphorous pentoxide for four hours under reduced pressure to obtain the desired compound 0.762 g.
Reaction SMILES: [CH:1]1([C:6]2[CH:7]=[C:8]([CH:11]=[CH:12][C:13]=2[O:14][CH3:15])[CH:9]=O)[CH2:5][CH2:4][CH2:3][CH2:2]1.[NH:16]1[C:24]2[C:19](=[CH:20][CH:21]=[CH:22][N:23]=2)[CH2:18][C:17]1=[O:25]>>[CH:1]1([C:6]2[CH:7]=[C:8]([CH:11]=[CH:12][C:13]=2[O:14][CH3:15])[CH:9]=[C:18]2[C:19]3[C:24](=[N:23][CH:22]=[CH:21][CH:20]=3)[NH:16][C:17]2=[O:25])[CH2:5][CH2:4][CH2:3][CH2:2]1
Reactant: O=C1Cc2cccnc2N1
Reactant: COc1ccc(C=O)cc1C1CCCC1
Product: COc1ccc(C=C2C(=O)Nc3ncccc32)cc1C1CCCC1

Procedure:
3-Cyclopentyl-4-methoxybenzaldehyde was condensed with 7-aza-2-oxindole to give 0.25 g of 3-(3-cyclopentyl-4-methoxybenzylidene,)-1,3-dihydropyrrolo[2,3-bipyridin-2-one as a yellow-orange solid.
Reaction SMILES: [C:1]([C:4]1[CH:13]=[CH:12][C:7]([C:8]([O:10][CH3:11])=[O:9])=[CH:6][CH:5]=1)(=[S:3])[NH2:2].[F:14][C:15]([F:27])([F:26])[C:16]1[CH:25]=[CH:24][C:19]([C:20](=O)[CH2:21]Br)=[CH:18][CH:17]=1>>[F:14][C:15]([F:26])([F:27])[C:16]1[CH:17]=[CH:18][C:19]([C:20]2[N:2]=[C:1]([C:4]3[CH:13]=[CH:12][C:7]([C:8]([O:10][CH3:11])=[O:9])=[CH:6][CH:5]=3)[S:3][CH:21]=2)=[CH:24][CH:25]=1
Reactant: COC(=O)c1ccc(C(N)=S)cc1
Reactant: O=C(CBr)c1ccc(C(F)(F)F)cc1
Product: COC(=O)c1ccc(-c2nc(-c3ccc(C(F)(F)F)cc3)cs2)cc1
Yield: 61 %

Procedure:
In the same manner as in Example 28, methyl 4-thiocarbamoylbenzoate was reacted with 4-trifluoromethylphenacyl bromide to obtain methyl 4-[4-(4-trifluoromethylphenyl)-2-thiazoly]benzoate. The product was recrystallized from ethanol. Yield: 61%. Colorless prisms. Melting point: 156 to 158° C.
Reaction SMILES: [Cl:1][C:2]([Cl:12])=[CH:3][C@@H:4]1[C@H:6]([C:7](Cl)=[O:8])[C:5]1([CH3:11])[CH3:10].[C:13]1([C:19]2[CH:27]=[CH:26][CH:25]=[C:24]3[C:20]=2[CH2:21][CH:22]([OH:28])[CH2:23]3)[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1.N1C=CC=CC=1>C1(C)C=CC=CC=1>[Cl:1][C:2]([Cl:12])=[CH:3][C@@H:4]1[C@H:6]([C:7]([O:28][CH:22]2[CH2:21][C:20]3[C:24](=[CH:25][CH:26]=[CH:27][C:19]=3[C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=3)[CH2:23]2)=[O:8])[C:5]1([CH3:11])[CH3:10]
Reactant: OC1Cc2cccc(-c3ccccc3)c2C1
Reactant: CC1(C)[C@H](C=C(Cl)Cl)[C@@H]1C(=O)Cl
Solvent: c1ccncc1
Solvent: Cc1ccccc1
Product: CC1(C)[C@H](C=C(Cl)Cl)[C@@H]1C(=O)OC1Cc2cccc(-c3ccccc3)c2C1
Yield: 65.5 %

Procedure:
In a manner similar to Example 12A, the reaction of 1.54 g (0.007 mole) of (+)-cis-3-(2,2-dichloroethenyl)-2,2-dimethyl-cyclopropanecarbonyl chloride and 1.5 g (0.007 mole) of (+)-4-phenyl-2-indanol (EE≥95%) in the presence of 0.7 g (0.009 mole) of pyridine and 20 ml of toluene gave 1.84 g of (+)-4-phenyl-2-indanyl (+)-cis-3-(2,2-dichloroethenyl)-2,2-dimethylcyclopropanecarboxylate as an oil, EE≥95% (alcohol moiety). The nmr spectrum was consistent with the proposed structure.
Reaction SMILES: C(OC([O:7][C@@H:8]([C@H:10]1[C:25](=[O:26])[N:12]2[C:13]([C:19]([O:21]CC=C)=[O:20])=[C:14]([CH2:17]O)[C@H:15]([CH3:16])[C@H:11]12)[CH3:9])=O)C=C.[C:27]([O:30][CH2:31][C:32]1[S:36][C:35]2=[CH:37][N:38]=[CH:39][N:34]2[CH:33]=1)(=[O:29])[CH3:28]>>[OH:7][C@@H:8]([C@H:10]1[C:25](=[O:26])[N:12]2[C:13]([C:19]([O-:21])=[O:20])=[C:14]([CH2:17][N:38]3[CH:37]=[C:35]4[S:36][C:32]([CH2:31][O:30][C:27](=[O:29])[CH3:28])=[CH:33][N+:34]4=[CH:39]3)[C@H:15]([CH3:16])[C@H:11]12)[CH3:9]
Reactant: C=CCOC(=O)O[C@H](C)[C@H]1C(=O)N2C(C(=O)OCC=C)=C(CO)[C@H](C)[C@H]12
Reactant: CC(=O)OCc1cn2cncc2s1
Product: CC(=O)OCc1c[n+]2cn(CC3=C(C(=O)[O-])N4C(=O)[C@H]([C@@H](C)O)[C@H]4[C@H]3C)cc2s1
Yield: 13 %

Procedure:
The same procedure as in Example 1 was repeated except that 120 mg of allyl (1S,5R,6S)-6-[(1R)-1-allyloxycarbonyloxyethyl]-2-hydroxymethyl-1-methyl-1-carbapen-2-em-3-carboxylate and 97 mg of 2-acetoxymethylimidazo[5,1-b]thiazole were used, thereby obtaining 17.9 mg of the title compound.
Reaction SMILES: [CH:1]1([CH2:4][OH:5])[CH2:3][CH2:2]1.[H-].[Na+].[F:8][C:9]1[CH:10]=[C:11]([CH:15]=[C:16]([F:19])[C:17]=1F)[C:12]([OH:14])=[O:13].Cl>CN(C=O)C>[CH:1]1([CH2:4][O:5][C:17]2[C:16]([F:19])=[CH:15][C:11]([C:12]([OH:14])=[O:13])=[CH:10][C:9]=2[F:8])[CH2:3][CH2:2]1
Reactant: OCC1CC1
Reactant: O=C(O)c1cc(F)c(F)c(F)c1
Agent: Cl
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: O=C(O)c1cc(F)c(OCC2CC2)c(F)c1
Temperature: 25 °C
Reaction time: 0.25 h

Procedure:
To a solution of cyclopropylmethanol (5.62 mL) in DMF (30 mL) was added sodium hydride (60% oil, 2.84 g), and the mixture was stirred at room temperature for 15 min. To the reaction mixture was added 3,4,5-trifluorobenzoic acid (5.00 g), and the mixture was stirred at room temperature for 30 min. The reaction mixture was neutralized with 6 M hydrochloric acid, and the mixture was extracted with ethyl acetate. The obtained organic layer was washed with saturated brine, and dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. To a solution of the obtained residue in DMF (20 mL) were added potassium carbonate (3.92 g) and methyl iodide (1.77 mL), and the mixture was stirred with heating at 60° C. for 40 min. The reaction mixture was allowed to cool to room temperature, diluted with ethyl acetate, washed with saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure, and the obtained residue was purified by silica gel column chromatography (hexane/ethyl acetate). To a solution of the obtained oil in a mixed solvent of THF (20 mL) and methanol (20 mL) was added 2 M aqueous sodium hydroxide solution (28.8 mL), and the mixture was stirred with heating at 60° C. for 40 min. The reaction mixture was allowed to cool to room temperature, and neutralized with 6 M hydrochloric acid, and the mixture was extracted with ethyl acetate. The obtained organic layer was washed with saturated brine, and dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. The obtained solid was washed with hexane to give the title compound (5.32 g).
Reaction SMILES: [Si](Br)(C)(C)C.CS(C)=O.[C:10]1([CH2:16][CH:17]=O)[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1.[N:19]1([CH2:24][CH2:25][O:26][C:27]2[CH:32]=[CH:31][C:30]([NH:33][C:34]([NH2:36])=[S:35])=[CH:29][CH:28]=2)[CH2:23][CH2:22][CH2:21][CH2:20]1>CC#N>[C:10]1([C:16]2[S:35][C:34]([NH:33][C:30]3[CH:31]=[CH:32][C:27]([O:26][CH2:25][CH2:24][N:19]4[CH2:23][CH2:22][CH2:21][CH2:20]4)=[CH:28][CH:29]=3)=[N:36][CH:17]=2)[CH:11]=[CH:12][CH:13]=[CH:14][CH:15]=1
Reactant: NC(=S)Nc1ccc(OCCN2CCCC2)cc1
Reactant: O=CCc1ccccc1
Agent: C[Si](C)(C)Br
Solvent: CS(C)=O
Solvent: CC#N
Product: c1ccc(-c2cnc(Nc3ccc(OCCN4CCCC4)cc3)s2)cc1
Temperature: 0 °C
Reaction time: 0.83 h

Procedure:
Me3SiBr (0.052 mL, 0.384 mmol, 1.1 equiv) and DMSO (0.027 mL, 0.384 mmol, 1.1 equiv) are added sequentially and dropwise to a cold (0° C.) solution of phenylacetaldehyde (42 mg, 0.349 mmol) in CH3CN (0.66 mL), under an argon atmosphere. The resulting mixture is stirred at 0° C. for 50 min, allowed to warm to RT and to stir for 10 min. CH3CN (0.97 mL) is added to the reaction mixture, followed by addition of [4-(2-pyrrolidin-1-yl-ethoxy)-phenyl]-thiourea (93 mg, 0.349 mmol). The reaction mixture is heated to reflux for 80 min, allowed to cool to RT and concentrated in vacuo. Purification of the crude product by silica gel (20 g) column chromatography (CH2Cl2/MeOH, 90/10) affords the title compound: ES-MS: 366.0 [M+H]+; single peak at tR=6.33 min (System 1); Rf=0.11 (CH2Cl2/MeOH, 80/20).
Reaction SMILES: C(OC([N:8]1[CH2:13][CH2:12][CH:11]([N:14]2[CH2:18][CH2:17][C:16]([F:20])([F:19])[CH2:15]2)[CH2:10][CH2:9]1)=O)(C)(C)C.[ClH:21]>O1CCOCC1>[ClH:21].[F:20][C:16]1([F:19])[CH2:17][CH2:18][N:14]([CH:11]2[CH2:10][CH2:9][NH:8][CH2:13][CH2:12]2)[CH2:15]1
Reactant: CC(C)(C)OC(=O)N1CCC(N2CCC(F)(F)C2)CC1
Agent: Cl
Solvent: C1COCCO1
Product: FC1(F)CCN(C2CCNCC2)C1
Temperature: 25 °C
Reaction time: 1 h

Procedure:
4-(3,3-difluoro-pyrrolidin-1-yl)-piperidine-1-carboxylic acid tert-butyl ester (1.77 mmol) is treated with 4N HCl in 1,4-dioxane (6 mL) and stirred at room temperature for 1 h. The reaction mixture is concentrated in vacuo and the resulting residue is used for the next step without further purification.
Reaction SMILES: [C:1]([N:11]([C@@H:13]([CH3:21])[C:14]1[CH:19]=[CH:18][C:17](N)=[CH:16][CH:15]=1)[CH3:12])([O:3][CH2:4][C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1)=[O:2].N([O-])=[O:23].[Na+].C1(C)C=CC=CC=1>S(=O)(=O)(O)O.O>[C:1]([N:11]([C@@H:13]([CH3:21])[C:14]1[CH:19]=[CH:18][C:17]([OH:23])=[CH:16][CH:15]=1)[CH3:12])([O:3][CH2:4][C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1)=[O:2]
Reactant: C[C@@H](c1ccc(N)cc1)N(C)C(=O)OCc1ccccc1
Reactant: O=N[O-]
Agent: O=S(=O)(O)O
Agent: [Na+]
Solvent: O
Solvent: Cc1ccccc1
Product: C[C@@H](c1ccc(O)cc1)N(C)C(=O)OCc1ccccc1
Temperature: 82.5 °C
Reaction time: 0.5 h
Yield: 58.4 %

Procedure:
The above (S)-(-)-N-carbobenzyloxy-N-methyl-4-amino-α-methylbenzylamine (6.0 gm, assume 21 mmol) was dissolved in 2N sulfuric acid (63 mL) and cooled in an ice salt bath. A solution of sodium nitrite (1.6 gm, 23 mmol) in water (25 mL) was added over 15 min at 0-5° C. and the reaction stirred for another 0.5 hr. Toluene (100 mL) was then added and the reaction was rapidly heated to 80-85° C. on a steam bath. The reaction turned very dark and after 10 min was poured onto ice and extracted with 2 portions of ether. The ether layers were each washed with brine, combined, dried over sodium sulfate and evaporated. The residue was purified by flash chromatography using 20-30% ethyl acetate/hexanes to give 3.5 gm (58%) of the title compound.
Reaction SMILES: [C:1]([O:5][C:6]([N:8]([C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=1[C:20]#[N:21])[C@H:9]([C:11]([OH:13])=O)[CH3:10])=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH2:22]([NH:28][CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][CH3:34])[CH2:23][CH2:24][CH2:25][CH2:26][CH3:27].O.ON1C2C=CC=CC=2N=N1.Cl.C(N=C=NCCCN(C)C)C>CN(C)C=O.O>[CH2:29]([N:28]([CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH3:27])[C:11](=[O:13])[C@H:9]([CH3:10])[N:8]([C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=1[C:20]#[N:21])[C:6]([O:5][C:1]([CH3:2])([CH3:3])[CH3:4])=[O:7])[CH2:30][CH2:31][CH2:32][CH2:33][CH3:34]
Reactant: CCCCCCNCCCCCC
Reactant: C[C@@H](C(=O)O)N(C(=O)OC(C)(C)C)c1ccccc1C#N
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Agent: On1nnc2ccccc21
Solvent: CN(C)C=O
Solvent: O
Product: CCCCCCN(CCCCCC)C(=O)[C@H](C)N(C(=O)OC(C)(C)C)c1ccccc1C#N
Temperature: 25 °C
Reaction time: 8 h
Yield: 79.1 %

Procedure:
To a solution of 0.81 g of the crude N-t-butoxycarbonyl-(2-cyanophenyl)alanine and 0.67 g of dihexylamine in 8 ml of N,N-dimethylformamide were added 0.55 g of 1-hydroxybenzotriazole monohydrate and 0.69 g of N-ethyl-N′-dimethylaminopropylcarbodiimide hydrochloride, followed by stirring at room temperature overnight. The reaction mixture was poured into water and extracted with ethyl acetate. The extract was washed with 5% aqueous potassium bisulfate solution, a saturated aqueous sodium bicarbonate solution and a saturated sodium chloride solution, and dried over anhydrous sodium sulfate. After removal of the drying agent by filtration, the filtrate was concentrated under reduced pressure. The residue was purified by chromatography (silica gel; Wakogel C200 (manufactured by Wako Pure Chemicals), developing solvent; hexane-ethyl acetate=4:1) to give 1.01 g of N-t-butoxycarbonyl-(2-cyanophenyl)alanine dihexylamide.
Reaction SMILES: [O:1]1[CH2:5][CH:4]([NH2:6])[CH:3]([NH2:7])[CH2:2]1.Cl.N=[C:10](OC)[C:11]1[C:12]([CH3:22])=[CH:13][C:14]([CH3:21])=[C:15]([CH:20]=1)[C:16]([O:18][CH3:19])=[O:17].C(N(CC)CC)C>C(O)C>[CH3:21][C:14]1[CH:13]=[C:12]([CH3:22])[C:11]([C:10]2[NH:7][CH:3]3[CH2:2][O:1][CH2:5][CH:4]3[N:6]=2)=[CH:20][C:15]=1[C:16]([O:18][CH3:19])=[O:17]
Reactant: NC1COCC1N
Reactant: COC(=N)c1cc(C(=O)OC)c(C)cc1C
Agent: Cl
Solvent: CCO
Solvent: CCN(CC)CC
Product: COC(=O)c1cc(C2=NC3COCC3N2)c(C)cc1C
Temperature: 80 °C
Reaction time: 8 h
Yield: 47 %

Procedure:
Into around-bottom flask, was placed a solution of tetrahydrofuran-3,4-diamine (compound 466.3, 140 mg, 1.17 mmol, 1.00 equiv, 85%) in ethanol (6 mL). Methyl 5-(imino(methoxy)methyl)-2,4-dimethylbenzoate hydrochloride (compound 466.4, 300 mg, 0.930 mmol, 1.00 equiv) and triethylamine (140 mg, 1.38 mmol, 1.00 equiv) were added and the resulting solution was stirred overnight at 80° C., then concentrated in vacuo. The residue was purified by silica gel chromatography with dichloromethane/methanol (10:1) as the eluent to obtain the title compound as a brown oil (120 mg, 34%).
Reaction SMILES: [F:1][C:2]1[CH:29]=[CH:28][C:5]([CH2:6][N:7]2[C:15]3[C:10](=[CH:11][C:12](/[CH:16]=[C:17]4/[C:18](=[O:27])[N:19]([CH2:23][C:24](O)=[O:25])[C:20](=[O:22])[S:21]/4)=[CH:13][CH:14]=3)[CH:9]=[N:8]2)=[C:4]([C:30]([F:33])([F:32])[F:31])[CH:3]=1.[CH3:34][S:35]([NH2:38])(=[O:37])=[O:36]>>[F:1][C:2]1[CH:29]=[CH:28][C:5]([CH2:6][N:7]2[C:15]3[C:10](=[CH:11][C:12](/[CH:16]=[C:17]4/[C:18](=[O:27])[N:19]([CH2:23][C:24]([NH:38][S:35]([CH3:34])(=[O:37])=[O:36])=[O:25])[C:20](=[O:22])[S:21]/4)=[CH:13][CH:14]=3)[CH:9]=[N:8]2)=[C:4]([C:30]([F:32])([F:33])[F:31])[CH:3]=1
Reactant: O=C(O)CN1C(=O)S/C(=C\c2ccc3c(cnn3Cc3ccc(F)cc3C(F)(F)F)c2)C1=O
Reactant: CS(N)(=O)=O
Product: CS(=O)(=O)NC(=O)CN1C(=O)S/C(=C\c2ccc3c(cnn3Cc3ccc(F)cc3C(F)(F)F)c2)C1=O

Procedure:
2-[(5Z)-5-({1-[4-Fluoro-2-(trifluoromethyl)benzyl]-1H-indazol-5-yl}methylidene)-2,4-dioxo-1,3-thiazolidin-3-yl]-N-(methylsulfonyl)-acetamide was prepared from [(5Z)-5-({1-[4-fluoro-2-(trifluoromethyl)-benzyl]-1H-indazol-5-yl}methylidene)-2,4-dioxo-1,3-thiazolidin-3-yl]acetic acid (Example 122) following General Procedure L using methanesulfonic acid amide in place of the sulfamide.
Reaction SMILES: Cl[C:2]1[N:7]=[C:6]([C:8]([NH:10][C:11]2[NH:15][N:14]=[N:13][N:12]=2)=[O:9])[CH:5]=[N:4][CH:3]=1.[CH2:16]([NH2:18])[CH3:17].Cl>C(O)C>[CH2:16]([NH:18][C:2]1[N:7]=[C:6]([C:8]([NH:10][C:11]2[NH:15][N:14]=[N:13][N:12]=2)=[O:9])[CH:5]=[N:4][CH:3]=1)[CH3:17]
Reactant: CCN
Reactant: O=C(Nc1nnn[nH]1)c1cncc(Cl)n1
Agent: Cl
Solvent: CCO
Product: CCNc1cncc(C(=O)Nc2nnn[nH]2)n1

Procedure:
To a suspension of 2.26 g of 6-chloro-N-(1H-5-tetrazolyl)pyrazine-2-carboxamide in 30 ml of ethanol, 4.05 ml of 70%-ethylamine aqueous solution was added, and the mixture was heated for 24 hours at 80°-90 ° C. in a sealed tube. The reaction mixture was adjusted with ethanolic hydrogen chloride to pH 3. The precipitate was collected by filtration, and recrystalized from a mixture of dimethylsulfoxide and methanol affording 1.66 g of the desired compound as pale yellow needles, m.p. 272°-273.5 ° C. (decomp.).
Reaction SMILES: [NH:1]1[C:9]2[C:4](=[C:5]([C:10]3[N:11]=[C:12]([N:22]4[CH2:27][CH2:26][O:25][CH2:24][CH2:23]4)[C:13]4[CH:18]=[C:17]([C:19]([OH:21])=O)[S:16][C:14]=4[N:15]=3)[CH:6]=[CH:7][CH:8]=2)[CH:3]=[N:2]1.[CH2:28]([CH2:30][NH2:31])[OH:29]>>[OH:29][CH2:28][CH2:30][NH:31][C:19]([C:17]1[S:16][C:14]2[N:15]=[C:10]([C:5]3[CH:6]=[CH:7][CH:8]=[C:9]4[C:4]=3[CH:3]=[N:2][NH:1]4)[N:11]=[C:12]([N:22]3[CH2:27][CH2:26][O:25][CH2:24][CH2:23]3)[C:13]=2[CH:18]=1)=[O:21]
Reactant: O=C(O)c1cc2c(N3CCOCC3)nc(-c3cccc4[nH]ncc34)nc2s1
Reactant: NCCO
Product: O=C(NCCO)c1cc2c(N3CCOCC3)nc(-c3cccc4[nH]ncc34)nc2s1

Procedure:
45 mg of 2-(1H-indazol-4-yl)-4-morpholinothieno[2,3-d]pyrimidine-6-carboxylic acid 14 was coupled to ethanolamine via General Procedure B. The product was purified via reverse phase HPLC to give 10.2 mg of 128. MS (Q1) 425.1 (M)+.
Reaction SMILES: [CH2:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[CH2:3][CH:2]1[N:10]([CH2:18][C:19]1[CH:24]=[CH:23][C:22]([C:25]2[CH:30]=[CH:29][CH:28]=[C:27]([CH:31]=[O:32])[CH:26]=2)=[CH:21][CH:20]=1)[C:11](=[O:17])[O:12][C:13]([CH3:16])([CH3:15])[CH3:14].[CH3:33][C:34]1[CH:39]=[CH:38][C:37]([S:40]([CH2:43][N+:44]#[C-:45])(=[O:42])=[O:41])=[CH:36][CH:35]=1.[C-]#N.[Na+]>CCO.O>[CH2:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[CH2:3][CH:2]1[N:10]([CH2:18][C:19]1[CH:20]=[CH:21][C:22]([C:25]2[CH:30]=[CH:29][CH:28]=[C:27]([CH:31]3[O:32][CH:45]=[N:44][CH:43]3[S:40]([C:37]3[CH:38]=[CH:39][C:34]([CH3:33])=[CH:35][CH:36]=3)(=[O:42])=[O:41])[CH:26]=2)=[CH:23][CH:24]=1)[C:11](=[O:17])[O:12][C:13]([CH3:14])([CH3:15])[CH3:16]
Reactant: CC(C)(C)OC(=O)N(Cc1ccc(-c2cccc(C=O)c2)cc1)C1Cc2ccccc2C1
Reactant: [C-]#[N+]CS(=O)(=O)c1ccc(C)cc1
Agent: [C-]#N
Agent: [Na+]
Solvent: CCO
Solvent: O
Product: Cc1ccc(S(=O)(=O)C2N=COC2c2cccc(-c3ccc(CN(C(=O)OC(C)(C)C)C4Cc5ccccc5C4)cc3)c2)cc1
Reaction time: 0.5 h

Procedure:
To a solution of 1,1-dimethylethyl 2,3-dihydro-1H-inden-2-yl[(3′-formyl-4-biphenylyl)-methyl]carbamate (0.188 g; 0.44 mmol) and TosMIC (0.086 g; 0.44 mmol) in EtOH at room temperature was added NaCN (0.002 g; 0.04 mmol). The mixture was stirred 30 min, diluted with water and extracted with EtOAc (×3). combined organics were washed (water, brine), dried over Na2SO4 and concentrated in vacuo affording the title compound as a colorless gum, used without further purification. 1H NMR (400 MHz, DMSO-d6) δ ppm 1.35 (s, 9H), 2.41 (s, 3H), 2.99 (d, J=8.38 Hz, 4H), 4.50 (br. s., 2H), 5.65 (dd, J=5.98, 1.69 Hz, 1H), 5.96 (d, J=5.89 Hz, 1H), 7.07-7.18 (m, 5H), 7.25 (partially resolved dd, J=7.85 Hz, 1H), 7.28-7.34 (m, 2H), 7.40 (unresolved dd, 1H), 7.46-7.52 (m, 3H), 7.57-7.64 (m, 2H), 7.68 (dd, J=8.03, 1.25 Hz, 1H), 7.74 (d, J=1.25 Hz, 1H), 7.83-7.90 (m, 2H).
Reaction SMILES: I[C:2]1[CH:3]=[C:4]([CH2:8][C:9]([NH:11][C:12]2[CH:21]=[C:20]([Cl:22])[CH:19]=[CH:18][C:13]=2[C:14]([O:16][CH3:17])=[O:15])=[O:10])[CH:5]=[CH:6][CH:7]=1.[C:23]1([C:29]#[CH:30])[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1>C(N(CC)CC)C.O1CCCC1.[Cu]I.C1(C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)[Pd][P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[Cl:22][C:20]1[CH:19]=[CH:18][C:13]([C:14]([O:16][CH3:17])=[O:15])=[C:12]([NH:11][C:9](=[O:10])[CH2:8][C:4]2[CH:5]=[CH:6][CH:7]=[C:2]([C:30]#[C:29][C:23]3[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=3)[CH:3]=2)[CH:21]=1
Reactant: C#Cc1ccccc1
Reactant: COC(=O)c1ccc(Cl)cc1NC(=O)Cc1cccc(I)c1
Agent: [Cu]I
Agent: c1ccc([P]([Pd][P](c2ccccc2)(c2ccccc2)c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Solvent: CCN(CC)CC
Solvent: C1CCOC1
Product: COC(=O)c1ccc(Cl)cc1NC(=O)Cc1cccc(C#Cc2ccccc2)c1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
To a solution of methyl 2-(3-iodophenylacetamido)-4-chlorobenzoate (m.p. 100°-101° C.; prepared by the general procedure described above; 860 mg, 2 mmol) in triethylamine (20 ml) and tetrahydrofuran (5 ml), was added copper (I) iodide (5 mg), bis(triphenylphosphine)palladium (II) dichloride (20 mg) and phenylacetylene (0.33 ml, 306 mg, 3 mmol), and the mixture stirred overnight at room temperature and then for 5 h at reflux. The solvents were removed, the residue partitioned between ethyl acetate (30 ml) and aqueous citric acid (10%, 25 ml), and the organic layer washed with water (25 ml) and brine (25 ml). After drying (MgSO4), the solution was evaporated and the residue subjected to chromatography on silica gel (4:1 petrol-ethyl acetate as eluant) to afford methyl 4-chloro-2-(3-phenylethynylphenyl)acetamidobenzoate as a colourless gum (824mg); δH (CDCl3) 3.75 (2H, s, --CH2 --), 3.87 (3H, s, CO2Me), 7.03 (1H, dd, J 9.4 and 2.1 Hz, 5-H), 7.33-7.38 (5H, m, ArH), 7.48-7.55 (4H, m, ArH), 7.91 (1H, d, J 9.4 Hz, 6-H), 8.82 (1H, d, J 2.1 Hz, 3-H), and 11.14 (1H, br s, --NHCO--).
Reaction SMILES: [C:1]1([CH3:10])[CH:6]=[CH:5][C:4]([C:7](Cl)=[O:8])=[CH:3][CH:2]=1.[CH3:11][O:12][C:13]1[CH:14]=[C:15]2[C:20](=[CH:21][C:22]=1[O:23][CH3:24])[N:19]=[CH:18][N:17]=[C:16]2[NH:25][C:26]1[S:27][C:28]2[CH:34]=[C:33]([NH2:35])[CH:32]=[CH:31][C:29]=2[N:30]=1>>[CH3:11][O:12][C:13]1[CH:14]=[C:15]2[C:20](=[CH:21][C:22]=1[O:23][CH3:24])[N:19]=[CH:18][N:17]=[C:16]2[NH:25][C:26]1[S:27][C:28]2[CH:34]=[C:33]([NH:35][C:7](=[O:8])[C:4]3[CH:5]=[CH:6][C:1]([CH3:10])=[CH:2][CH:3]=3)[CH:32]=[CH:31][C:29]=2[N:30]=1
Reactant: COc1cc2ncnc(Nc3nc4ccc(N)cc4s3)c2cc1OC
Reactant: Cc1ccc(C(=O)Cl)cc1
Product: COc1cc2ncnc(Nc3nc4ccc(NC(=O)c5ccc(C)cc5)cc4s3)c2cc1OC

Procedure:
N-[2-(6,7-Dimethoxyquinazolin-4-ylamino)benzothiazol-6-yl]-4-methylbenzamide was prepared from p-toluoyl chloride (17.5 mg, 0.113 mmol) and N2-(6,7-dimethoxyquinazolin-4-yl)benzothiazole-2,6-diamine (40 mg, 0.113 mmol) according to GP 2 (yellowish solid, 44 mg, 93 μmol, 82%). LC/ESI-MS: m/z=472 [M+H]+; m/z=470 [M−H]−; R′, =3.32 min.