Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [NH2:1][C@H:2]([C:15]([N:17]1[CH2:63][CH2:62][CH2:61][C@H:18]1[C:19]([N:21]1[CH2:60][CH2:59][CH2:58][C@H:22]1[C:23]([NH:25][C@H:26]([C:52]([C:54]([CH3:57])([CH3:56])[CH3:55])=[O:53])[CH2:27][CH2:28][CH2:29][NH:30][C:31](=[NH:51])[NH:32][S:33]([C:36]1[C:49]([CH3:50])=[C:47]([CH3:48])[C:46]2[O:45][C:42]([CH3:44])([CH3:43])[CH2:41][CH2:40][C:39]=2[C:37]=1[CH3:38])(=[O:35])=[O:34])=[O:24])=[O:20])=[O:16])[CH2:3][CH2:4][CH2:5][CH2:6][NH:7][C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9].[NH:64]([C:76]([O:78][CH2:79][CH:80]1[C:92]2[C:87](=[CH:88][CH:89]=[CH:90][CH:91]=2)[C:86]2[C:81]1=[CH:82][CH:83]=[CH:84][CH:85]=2)=[O:77])[C@H:65]([C:73](O)=[O:74])[C@@H:66]([CH3:72])[O:67][C:68]([CH3:71])([CH3:70])[CH3:69].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>C(Cl)Cl>[NH:64]([C:76]([O:78][CH2:79][CH:80]1[C:92]2[C:87](=[CH:88][CH:89]=[CH:90][CH:91]=2)[C:86]2[C:81]1=[CH:82][CH:83]=[CH:84][CH:85]=2)=[O:77])[C@H:65]([C:73]([NH:1][C@H:2]([C:15]([N:17]1[CH2:63][CH2:62][CH2:61][C@H:18]1[C:19]([N:21]1[CH2:60][CH2:59][CH2:58][C@H:22]1[C:23]([NH:25][C@H:26]([C:52]([C:54]([CH3:55])([CH3:57])[CH3:56])=[O:53])[CH2:27][CH2:28][CH2:29][NH:30][C:31](=[NH:51])[NH:32][S:33]([C:36]1[C:49]([CH3:50])=[C:47]([CH3:48])[C:46]2[O:45][C:42]([CH3:43])([CH3:44])[CH2:41][CH2:40][C:39]=2[C:37]=1[CH3:38])(=[O:35])=[O:34])=[O:24])=[O:20])=[O:16])[CH2:3][CH2:4][CH2:5][CH2:6][NH:7][C:8]([O:10][C:11]([CH3:13])([CH3:12])[CH3:14])=[O:9])=[O:74])[C@@H:66]([CH3:72])[O:67][C:68]([CH3:70])([CH3:71])[CH3:69]
Reactant: Cc1c(C)c(S(=O)(=O)NC(=N)NCCC[C@H](NC(=O)[C@@H]2CCCN2C(=O)[C@@H]2CCCN2C(=O)[C@@H](N)CCCCNC(=O)OC(C)(C)C)C(=O)C(C)(C)C)c(C)c2c1OC(C)(C)CC2
Reactant: C[C@@H](OC(C)(C)C)[C@H](NC(=O)OCC1c2ccccc2-c2ccccc21)C(=O)O
Agent: CN(C)C(On1nnc2cccnc21)=[N+](C)C
Agent: F[P-](F)(F)(F)(F)F
Solvent: CCN(C(C)C)C(C)C
Solvent: ClCCl
Product: Cc1c(C)c(S(=O)(=O)NC(=N)NCCC[C@H](NC(=O)[C@@H]2CCCN2C(=O)[C@@H]2CCCN2C(=O)[C@H](CCCCNC(=O)OC(C)(C)C)NC(=O)[C@@H](NC(=O)OCC2c3ccccc3-c3ccccc32)[C@@H](C)OC(C)(C)C)C(=O)C(C)(C)C)c(C)c2c1OC(C)(C)CC2
Temperature: 25 °C
Reaction time: 20 h

Procedure:
H-Lys(Boc)-Pro-Pro-Arg(Pmc)-t-Bu (3.55 g, 3.86 m mmol) was added to a solution of the activated acid prepared from Fmoc-Thr(t-Bu)-OH (1.6 g, 4 mmol) and HATU (1.9 g, 5 mmol) and DIEA (1.29 g, 10 mmol) in dry CH2Cl2 (25 ml) and stirred for 20 h at RT.
Reaction SMILES: [CH3:1][C:2]1[CH:3]=[C:4]([NH:8][C:9](=[O:22])[NH:10][CH:11]([CH2:15][C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)[C:12]([OH:14])=O)[CH:5]=[CH:6][CH:7]=1.[NH:23]([CH2:30][C:31]([O:33][C:34]([CH3:37])([CH3:36])[CH3:35])=[O:32])[C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1>ClCCCl.S(Cl)(Cl)=O>[CH3:1][C:2]1[CH:3]=[C:4]([NH:8][C:9](=[O:22])[NH:10][CH:11]([CH2:15][C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)[C:12]([N:23]([C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)[CH2:30][C:31]([O:33][C:34]([CH3:37])([CH3:35])[CH3:36])=[O:32])=[O:14])[CH:5]=[CH:6][CH:7]=1
Reactant: CC(C)(C)OC(=O)CNc1ccccc1
Reactant: Cc1cccc(NC(=O)NC(Cc2ccccc2)C(=O)O)c1
Solvent: O=S(Cl)Cl
Solvent: ClCCCl
Product: Cc1cccc(NC(=O)NC(Cc2ccccc2)C(=O)N(CC(=O)OC(C)(C)C)c2ccccc2)c1
Yield: 41.2 %

Procedure:
Working as in Example 15, but starting with (RS)-2-[3-(3-methylphenyl)ureido]-3-phenylpropanoic acid (4.8 g) and tert-butyl anilinoacetate (3.3 g) in anhydrous 1,2-dichloroethane (300 cc) and thionyl chloride (1.16 cc), and recrystallizing successively in diethyl ether and then in isopropanol, tert-butyl (RS)-N-{2-[3-(3-methylphenyl)ureido]-3-phenylpropionyl}-N-phenylglycinate (3.2 g), m.p. 198° C., is obtained.
Reaction SMILES: P(Cl)(Cl)([Cl:3])=O.[CH3:6][O:7][C:8]([C:10]1[CH:11]=[C:12]2[C:17](=[CH:18][CH:19]=1)[N+:16]([O-])=[CH:15][CH:14]=[CH:13]2)=[O:9]>C(OCC)(=O)C>[CH3:6][O:7][C:8]([C:10]1[CH:11]=[C:12]2[C:17](=[CH:18][CH:19]=1)[N:16]=[C:15]([Cl:3])[CH:14]=[CH:13]2)=[O:9]
Reactant: COC(=O)c1ccc2c(ccc[n+]2[O-])c1
Reactant: O=P(Cl)(Cl)Cl
Solvent: CCOC(C)=O
Product: COC(=O)c1ccc2nc(Cl)ccc2c1
Temperature: 25 °C
Yield: 28 %

Procedure:
Phosphorus oxychloride (10 mL) was added to quinoline-6-carboxylic acid methyl ester N-oxide (1.5 g, 7.6 mmol), and the solution was refluxed for 2 hours. The reaction solution was poured onto an ice, and warmed gradually to room temperature. Ethyl acetate was added to the reaction solution, which was then extracted, and sequentially washed with an aqueous solution of saturated sodium bicarbonate and brine. The solvent was evaporated in vacuo, the residue was purified by silica gel column chromatography (hexane:ethyl acetate=2:1), and the title compound (0.47 g, 2.1 mmol, 28%) was obtained as a white solid.
Reaction SMILES: [NH:1]([C:5]1[CH:11]=[CH:10][C:8]([OH:9])=[CH:7][CH:6]=1)[C:2]([CH3:4])=[O:3].[Br:12][CH2:13][C:14](Cl)=[O:15]>C1COCC1>[Br:12][CH2:13][C:14]([O:9][C:8]1[CH:10]=[CH:11][C:5]([NH:1][C:2](=[O:3])[CH3:4])=[CH:6][CH:7]=1)=[O:15]
Reactant: CC(=O)Nc1ccc(O)cc1
Reactant: O=C(Cl)CBr
Solvent: C1CCOC1
Product: CC(=O)Nc1ccc(OC(=O)CBr)cc1
Temperature: 25 °C
Reaction time: 24 h
Yield: 27.8 %

Procedure:
TEA (0.28 ml, 1.98 mmol, 3.0 eq) was added to a solution of paracetamol [4147] (0.10 g, 0.66 mmol, 1.0 eq) of in dry THF under argon atmosphere. At 0° C., bromoacetyl chloride [244] (0.123 g, 0.79 mmol, 1.2 eq) was added. The reaction mixture was stirred at room temperature for 24 h. After 24 h, solvent was evaporated under vacuum and residue was taken in dichloromethane (50 ml) and washed with a 10% solution of NaHCO3 (15 ml) and then with brine (10 ml), followed by drying of the organic layer over anhydrous sodium sulfate. Evaporation of the solvent provided white solid which was purified by silica gel column chromatography (0.5% MeOH: DCM, 100-200 mesh silica) to give the product 4-acetamidophenyl 2-bromoacetate [299] (0.05 g, 28%).
Reaction SMILES: [NH2:1][C:2]1[C:3](=[O:17])[N:4]([CH2:9][C:10]([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11])[C:5]([CH3:8])=[CH:6][CH:7]=1.[CH2:18]([S:22](Cl)(=[O:24])=[O:23])[CH2:19][CH2:20][CH3:21]>>[CH2:18]([S:22]([NH:1][C:2]1[C:3](=[O:17])[N:4]([CH2:9][C:10]([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11])[C:5]([CH3:8])=[CH:6][CH:7]=1)(=[O:24])=[O:23])[CH2:19][CH2:20][CH3:21]
Reactant: CCCCS(=O)(=O)Cl
Reactant: Cc1ccc(N)c(=O)n1CC(=O)OC(C)(C)C
Product: CCCCS(=O)(=O)Nc1ccc(C)n(CC(=O)OC(C)(C)C)c1=O

Procedure:
The title compound was prepared from tert-butyl 2-[3-amino-6-methyl-2-oxo-1(2H)-pyridinyl]acetate (EXAMPLE 1, STEP 1-3), and 1-butanesulfonyl chloride using the procedure of EXAMPLE 9 (STEP 2). The product was recrystallized from ethylacetate to give a white crystalline solid compound.
Reaction SMILES: C[Si](C)(C)[O:3][C:4]([CH:6]=[CH2:7])=[CH2:5].[CH2:10]([NH:12][CH2:13][CH2:14][CH3:15])[CH3:11].B(F)(F)F.CCOCC.Cl>C(Cl)Cl>[CH2:10]([N:12]1[CH2:7][CH2:6][C:4](=[O:5])[CH2:3][CH:13]1[CH2:14][CH3:15])[CH3:11]
Reactant: C=CC(=C)O[Si](C)(C)C
Reactant: CCCNCC
Agent: Cl
Agent: FB(F)F
Solvent: CCOCC
Solvent: ClCCl
Product: CCC1CC(=O)CCN1CC

Procedure:
To 100 mL of methylene chloride cooled to 0° C. is added 2-(trimethylsilyloxy)-1,3-butadiene (14.2 g, 0.1 mol), 8.5 g (0.1 mol) of N-ethyl-propanamine, and 14.2 g (0.1 mol) of borontrifluoride etherate. Monitor the reaction by thinlayer chromatography. Upon completion add 1N HCl until gas evolution ceases. Separate the aqueous layer and make it alkaline with 1N NaOH. Extract twice with 100 mL ether and dry over Na2SO4. Filter the drying agent and evaporated the solvent in vacuo to obtain the title compound.
Reaction SMILES: Cl[C:2]1[N:3]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)[C:4]2[C:9]([C:10]=1[CH:11]=[O:12])=[CH:8][CH:7]=[CH:6][CH:5]=2.[OH:19][CH2:20][CH2:21][N:22]1[CH2:27][CH2:26][NH:25][CH2:24][CH2:23]1>O1CCOCC1.O>[OH:19][CH2:20][CH2:21][N:22]1[CH2:27][CH2:26][N:25]([C:2]2[N:3]([C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=3)[C:4]3[C:9]([C:10]=2[CH:11]=[O:12])=[CH:8][CH:7]=[CH:6][CH:5]=3)[CH2:24][CH2:23]1
Reactant: O=Cc1c(Cl)n(-c2ccccc2)c2ccccc12
Reactant: OCCN1CCNCC1
Solvent: O
Solvent: C1COCCO1
Product: O=Cc1c(N2CCN(CCO)CC2)n(-c2ccccc2)c2ccccc12

Procedure:
2-Chloro-1-phenyl-1H-indole-3-carboxaldehyde (2.55 g, 19.6 mmol), 4-(2-hydroxyethyl)-piperazine (1.00 g, 3.92 mmol) in dioxane (13 mL) is heated overnight at reflux. The cooled reaction is diluted with water and extracted with dichloromethane. The organic layer is dried, filtered and evaporated to a semi-solid that is triturated with ether to give the 2-[4-(2-hydroxyethyl)piperazin-1-yl]-1-phenyl-1H-indole-3-carboxaldehyde as a brownish solid. MS 350 (M+H).
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:16]3[C:11](=[CH:12][C:13]([O:17][C@@H:18]([C:22]4[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=4)[C@H:19]([NH2:21])[CH3:20])=[CH:14][CH:15]=3)[CH:10]=[N:9]2)=[CH:4][CH:3]=1.[F:28][CH:29](F)[C:30](Cl)=[O:31]>>[F:28][CH2:29][C:30]([NH:21][C@@H:19]([CH3:20])[C@H:18]([O:17][C:13]1[CH:12]=[C:11]2[C:16](=[CH:15][CH:14]=1)[N:8]([C:5]1[CH:4]=[CH:3][C:2]([F:1])=[CH:7][CH:6]=1)[N:9]=[CH:10]2)[C:22]1[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=1)=[O:31]
Reactant: C[C@@H](N)[C@@H](Oc1ccc2c(cnn2-c2ccc(F)cc2)c1)c1ccccc1
Reactant: O=C(Cl)C(F)F
Product: C[C@H](NC(=O)CF)[C@H](Oc1ccc2c(cnn2-c2ccc(F)cc2)c1)c1ccccc1

Procedure:
Prepared as described in Example 1 using (1S,2R)-1-{[1-(4-fluorophenyl)-1H-indazol-5-yl]oxy}-1-phenylpropan-2-amine (1a, 36 mg, 100 μmol) and difluoroacetyl chloride (29 mg, 300 μmol). Yield 40 mg (95%).
Reaction SMILES: Cl[C:2]1[C:3](=[O:16])[N:4]([CH3:15])[S:5](=[O:14])(=[O:13])[C:6]=1[C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1.[CH3:17][O:18][C:19]1[CH:25]=[CH:24][C:22]([NH2:23])=[CH:21][CH:20]=1>>[CH3:17][O:18][C:19]1[CH:25]=[CH:24][C:22]([NH:23][C:2]2[C:3](=[O:16])[N:4]([CH3:15])[S:5](=[O:14])(=[O:13])[C:6]=2[C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=2)=[CH:21][CH:20]=1
Reactant: COc1ccc(N)cc1
Reactant: CN1C(=O)C(Cl)=C(c2ccccc2)S1(=O)=O
Product: COc1ccc(NC2=C(c3ccccc3)S(=O)(=O)N(C)C2=O)cc1

Procedure:
The title compound was prepared from 4-chloro-2-methyl-5-phenylisothiazol-3(2H)-one 1,1-dioxide and 4-methoxyaniline in a similar manner as described for e.g. Examples 9 and 13. 1H NMR (400 MHz, CD3CN): δ 7.67 (bs, 1H), 7.27-7.22 (m, 1H), 7.18-7.10 (m, 4H), 6.78-6.73 (m, 2H), 6.57-6.52 (m, 2H), 3.65 (s, 3H), 3.20 (s, 3H); Mass Spectrum: M+H+ 345.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]([P:13]([C:26]2[CH:31]=[C:30]([O:32][CH3:33])[C:29]([O:34][CH3:35])=[C:28]([O:36][CH3:37])[CH:27]=2)[C:14]2[CH:19]=[C:18]([O:20][CH3:21])[C:17]([O:22][CH3:23])=[C:16]([O:24][CH3:25])[CH:15]=2)[CH:6]=[C:7]([O:11][CH3:12])[C:8]=1[O:9][CH3:10].OO.S([O-])([O-])=[O:41].[Na+].[Na+]>C(Cl)Cl.C(O)C>[CH3:21][O:20][C:18]1[CH:19]=[C:14]([P:13](=[O:41])([C:5]2[CH:6]=[C:7]([O:11][CH3:12])[C:8]([O:9][CH3:10])=[C:3]([O:2][CH3:1])[CH:4]=2)[C:26]2[CH:27]=[C:28]([O:36][CH3:37])[C:29]([O:34][CH3:35])=[C:30]([O:32][CH3:33])[CH:31]=2)[CH:15]=[C:16]([O:24][CH3:25])[C:17]=1[O:22][CH3:23]
Reactant: COc1cc(P(c2cc(OC)c(OC)c(OC)c2)c2cc(OC)c(OC)c(OC)c2)cc(OC)c1OC
Reactant: O=S([O-])[O-]
Agent: OO
Agent: [Na+]
Solvent: ClCCl
Solvent: CCO
Product: COc1cc(P(=O)(c2cc(OC)c(OC)c(OC)c2)c2cc(OC)c(OC)c(OC)c2)cc(OC)c1OC
Temperature: 0 °C
Reaction time: 2 h

Procedure:
31.6 g (59.3 mmol) of tris(3,4,5-trimethoxyphenyl)phosphine were dissolved in a mixture of 100 ml of methylene chloride and 150 ml of ethanol in a 500 ml four-necked sulphonation flask having a thermometer, mechanical stirrer, 100 ml dropping funnel and condenser. 6.8 g (60 mmol) of 30% hydrogen peroxide were added dropwise to the resulting solution within 15 min., with the reaction temperature being held at 15-20° C. Shortly after completion of the dropwise addition of hydrogen peroxide the reaction had finished according to TLC. The reaction solution obtained was treated with 5 ml of saturated sodium sulphite solution, following which peroxide could no longer be detected in the reaction mixture. The reaction mixture was treated with 200 ml of methylene chloride and extracted twice with 300 ml of deionized water. The combined phases were re-extracted with 300 ml of methylene chloride, washed with 300 ml of saturated sodium chloride solution, dried over magnesium sulphate, filtered and treated with 200 ml of hexane. The solution obtained was concentrated on a RV at 50° C./600 mbar, with crystallization setting in. After stirring at 0° C. for 2 h. the crystalline material was filtered off under suction, washed twice with 50 ml of hexane and dried for 2 h. at 100° C. in a HV. 13.0 g of tris(3,4,5-trimethoxyphenyl)phosphine oxide were isolated at a first crystallizate. A further 12.7 g of tris(3,4,5-trimethoxyphenyl)phosphine oxide were obtained from the mother liquor as a second crystallizate. Both crystallizates were identical and uniform. The total yield of tris(3,4,5-trimethoxyphenyl)phosphine oxide was 25.7 g (79%).
Reaction SMILES: [OH:1][C:2]([C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1)([C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1)[CH2:3][CH2:4][CH2:5][CH2:6][N:7]1C(=O)C2C(=CC=CC=2)C1=O.O.NN>C(O)C>[OH:1][C:2]([C:24]1[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=1)([C:18]1[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=1)[CH2:3][CH2:4][CH2:5][CH2:6][NH2:7]
Reactant: O=C1c2ccccc2C(=O)N1CCCCC(O)(c1ccccc1)c1ccccc1
Agent: NN
Solvent: CCO
Solvent: O
Product: NCCCCC(O)(c1ccccc1)c1ccccc1

Procedure:
Batch size: 5.0 g (13.0 mmol) 2-(5-hydroxy-5,5-diphenyl-pentyl)-isoindol-1,3-dione and 1.3 g (26.0 mmol) hydrazine hydrate in 50 ml ethanol.
Reaction SMILES: [NH2:1][CH:2]([CH2:12][C:13]1[O:14][C:15]([C:18]([F:21])([F:20])[F:19])=[CH:16][CH:17]=1)[CH:3]([C:5]1[CH:10]=[CH:9][C:8]([F:11])=[CH:7][CH:6]=1)[OH:4].[C:22]1([CH2:28][CH2:29][C:30](Cl)=[O:31])[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1.C(=O)([O-])O.[Na+]>C(OCC)(=O)C.O>[F:11][C:8]1[CH:9]=[CH:10][C:5]([CH:3]([OH:4])[CH:2]([NH:1][C:30](=[O:31])[CH2:29][CH2:28][C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)[CH2:12][C:13]2[O:14][C:15]([C:18]([F:21])([F:20])[F:19])=[CH:16][CH:17]=2)=[CH:6][CH:7]=1
Reactant: NC(Cc1ccc(C(F)(F)F)o1)C(O)c1ccc(F)cc1
Reactant: O=C(Cl)CCc1ccccc1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CCOC(C)=O
Solvent: O
Product: O=C(CCc1ccccc1)NC(Cc1ccc(C(F)(F)F)o1)C(O)c1ccc(F)cc1
Temperature: 25 °C
Reaction time: 8 h
Yield: 74.5 %

Procedure:
To a solution of (1RS,2SR)-2-amino-1-(4-fluorophenyl)-3-(5-(trifluoromethyl)-2-furanyl)-1-propanol (300 mg, 099 mmol) in ethyl acetate (10 ml) were added 3-phenylpropionyl chloride (220 ml, 1.48 mmol) and saturated aqueous sodium hydrogen carbonate (10 ml) and the mixture was stirred overnight at room temperature. The reaction solution was diluted with water (100 ml) and extracted with ethyl acetate (100 ml×2). The extract was washed with saturated brine, dried over anhydrous magnesium sulfate and evaporated under reduced pressure. The residue was recrystallized from ethyl acetate-hexane to give the title compound (321 mg, 75%).
Reaction SMILES: I[C:2]1[CH:7]=[CH:6][C:5]([C:8]([F:11])([F:10])[F:9])=[CH:4][C:3]=1[C@H:12]1[O:16][C:15](=[O:17])[NH:14][C@@H:13]1[CH3:18].[F:19][C:20]1[C:25]([CH:26]([CH3:28])[CH3:27])=[CH:24][C:23](B(O)O)=[C:22]([O:32][CH3:33])[CH:21]=1>>[F:19][C:20]1[C:25]([CH:26]([CH3:28])[CH3:27])=[CH:24][C:23]([C:2]2[CH:7]=[CH:6][C:5]([C:8]([F:11])([F:10])[F:9])=[CH:4][C:3]=2[C@H:12]2[O:16][C:15](=[O:17])[NH:14][C@@H:13]2[CH3:18])=[C:22]([O:32][CH3:33])[CH:21]=1
Reactant: C[C@H]1NC(=O)O[C@@H]1c1cc(C(F)(F)F)ccc1I
Reactant: COc1cc(F)c(C(C)C)cc1B(O)O
Product: COc1cc(F)c(C(C)C)cc1-c1ccc(C(F)(F)F)cc1[C@H]1OC(=O)N[C@@H]1C

Procedure:
Following the procedure described in EXAMPLE 81, 240 mg of (4R,5R)-5-[2-iodo-5-(trifluoromethyl)phenyl]-4-methyl-1,3-oxazolidin-2-one and 171 mg of (4-fluoro-5-isopropyl-2-methoxyphenyl)boronic acid (EXAMPLE 78) gave the title compound. Mass spectrum (ESI) 412.3 (M+1). 1H NMR signals are doubled because of atropoisomerism. 1H NMR (500 MHz, CDCl3): δ 7.79, 7.77 (s, 1H), 7.64, 7.62 (dd, J˜2.5 Hz, 8 Hz, 1H), 7.32, 7.31 (d, J˜8 Hz, 1H), 7.00, 6.95 (d, J=8.5 Hz, 1H), 6.70, 6.67 (d, J=12 Hz, 1H), 6.47, 6.43 (s, 1H), 5.08, 5.04 (d, J=5 Hz, 0.1H), 3.68-3.80 (m, 3.5H), 3.53 (m, 0.5H), 3.21 (m, 1H), 1.19-1.30 (m, 6H), 0.95, 0.77 (d, J=6 Hz, 3H).
Reaction SMILES: FC(F)(F)C(O)=O.C(OC(=O)[NH:14][CH:15]1[CH2:20][CH2:19][N:18]([CH2:21][CH2:22][S:23][C:24]2[CH:25]=[N:26][C:27]3[C:32]([CH:33]=2)=[CH:31][C:30]([O:34][CH3:35])=[CH:29][CH:28]=3)[CH2:17][CH2:16]1)(C)(C)C>ClCCl>[CH3:35][O:34][C:30]1[CH:31]=[C:32]2[C:27](=[CH:28][CH:29]=1)[N:26]=[CH:25][C:24]([S:23][CH2:22][CH2:21][N:18]1[CH2:19][CH2:20][CH:15]([NH2:14])[CH2:16][CH2:17]1)=[CH:33]2
Reactant: COc1ccc2ncc(SCCN3CCC(NC(=O)OC(C)(C)C)CC3)cc2c1
Solvent: O=C(O)C(F)(F)F
Solvent: ClCCl
Product: COc1ccc2ncc(SCCN3CCC(N)CC3)cc2c1
Temperature: 25 °C
Reaction time: 15 h
Yield: 106.4 %

Procedure:
Trifluoroacetic acid (1.88 mL, 24.2 mmol, 15.0 eq) is added at 0° C. to a stirred solution of {1-[2-(6-methoxy-quinolin-3-ylsulfanyl)-ethyl]-piperidin-4-yl}-carbamic acid tert-butyl ester (724 mg, 1.61 mmol, 1.0 eq) in dichloromethane (75 mL). After 15 hours stirring at room temperature, the reaction mixture is extracted with dichloromethane (3×50 mL) and water (50 mL) and the pH value adjusted to 12 by the addition of a 1N sodium hydroxide aqueous solution. The combined organic layers are dried over sodium sulfate, filtered and concentrated to afford 1-[2-(6-methoxy-quinolin-3-ylsulfanyl)-ethyl]-piperidin-4-ylamine as a brown oil (544 mg, 99% yield).
Reaction SMILES: [C:1]1([C:7]2[N:22]=[C:10]3[CH:11]=[C:12]([C:16]4[CH:21]=[CH:20][N:19]=[CH:18][CH:17]=4)[CH:13]=[C:14]([NH2:15])[N:9]3[N:8]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[C:23](Cl)(=[O:25])[CH3:24]>>[C:1]1([C:7]2[N:22]=[C:10]3[CH:11]=[C:12]([C:16]4[CH:21]=[CH:20][N:19]=[CH:18][CH:17]=4)[CH:13]=[C:14]([NH:15][C:23](=[O:25])[CH3:24])[N:9]3[N:8]=2)[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1
Reactant: Nc1cc(-c2ccncc2)cc2nc(-c3ccccc3)nn12
Reactant: CC(=O)Cl
Product: CC(=O)Nc1cc(-c2ccncc2)cc2nc(-c3ccccc3)nn12

Procedure:
The title compound, MS m/e (%): 330 (M+H+, 100), was prepared in accordance with the general method of example 31 from 2-phenyl-7-pyridin-4-yl-[1,2,4]triazolo[1,5-a]pyridin-5-ylamine and acetylchloride.
Reaction SMILES: Br[C:2]1[CH:11]=[CH:10][CH:9]=[C:8]2[C:3]=1[C:4](=[O:14])[N:5]([CH3:13])[C:6](=[O:12])[NH:7]2.[CH3:15][Si:16]([C:19]#[CH:20])([CH3:18])[CH3:17].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>CN(C=O)C.C(N(CC)CC)C.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH3:13][N:5]1[C:4](=[O:14])[C:3]2[C:8](=[CH:9][CH:10]=[CH:11][C:2]=2[C:20]#[C:19][Si:16]([CH3:18])([CH3:17])[CH3:15])[NH:7][C:6]1=[O:12]
Reactant: C#C[Si](C)(C)C
Reactant: Cn1c(=O)[nH]c2cccc(Br)c2c1=O
Agent: [Pd+2]
Agent: CC(=O)[O-]
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: CCN(CC)CC
Solvent: CN(C)C=O
Product: Cn1c(=O)[nH]c2cccc(C#C[Si](C)(C)C)c2c1=O
Temperature: 70 °C
Reaction time: 4 h
Yield: 45.9 %

Procedure:
To a degassed solution of 5-bromo-3-methyl-2,4-dioxo-1,2,3,4-tetrahydro-quinazoline (1.0 g, 4.0 mmol) in 20 ml of DMF and 20 ml of triethylamine was added trimethylsilylacetylene (1.6 ml, 12 mmol), 50 mg of triphenylphosphine, 20 mg of palladium(II)acetate, and 1 mg of cuprous(I)iodide. The mixture was stirred under nitrogen, at 70° C. After 7 h additionally 0.4 ml of trimethylsilylacetylene was added and heating continued for 4 h. Then the mixture was evaporated in vacuo and the residue extracted with 100 ml of dichloromethane and 100 ml of water. The organic layer was washed twice with 100 ml of water, dried over anhydrous sodium sulfate, treated with charcoal, filtered through a pad of celite, and evaporated. The residue was triturated with ether/petroleum ether (1:1) and filtered off and dried giving 0.50 g (46%) of 1,2,3,4-tetrahydro-3-methyl-2,4-dioxo-5-trimethylsilylethynyl-quinazoline.
Reaction SMILES: [CH3:1][O:2][C:3]1[C:8]([O:9][CH3:10])=[CH:7][N:6]=[C:5]([CH2:11][S:12][C:13]2[NH:17][C:16]3[CH:18]=[CH:19][C:20]([O:22][CH2:23][C:24]([F:27])([F:26])[F:25])=[CH:21][C:15]=3[N:14]=2)[CH:4]=1.Cl[O-].[Na+].S([O-])([O-])(=[O:33])=S.[Na+].[Na+]>O1CCOCC1.[OH-].[Na+]>[CH3:1][O:2][C:3]1[C:8]([O:9][CH3:10])=[CH:7][N:6]=[C:5]([CH2:11][S:12]([C:13]2[NH:17][C:16]3[CH:18]=[CH:19][C:20]([O:22][CH2:23][C:24]([F:27])([F:26])[F:25])=[CH:21][C:15]=3[N:14]=2)=[O:33])[CH:4]=1
Reactant: COc1cnc(CSc2nc3cc(OCC(F)(F)F)ccc3[nH]2)cc1OC
Reactant: O=S([O-])([O-])=S
Agent: [Na+]
Agent: [O-]Cl
Agent: [OH-]
Solvent: C1COCCO1
Product: COc1cnc(CS(=O)c2nc3cc(OCC(F)(F)F)ccc3[nH]2)cc1OC

Procedure:
0.8 g of 2-[(4,5-dimethoxy-2-pyridyl)methylthio]-5-(2,2,2-trifluoroethoxy)-1H-benzimidazole is dissolved in 15 ml of dioxane and 2.5 ml of 1N sodium hydroxide solution. A mixture of 3 ml of 8% strength sodium hypochlorite solution and 3.5 ml of 1N sodium hydroxide solution are added dropwise in the course of 2 hours, while cooling to 0°-5° C. After addition of 5 ml of 5% strength sodium thiosulfate solution, the mixture is concentrated to dryness, the residue is taken up in water and the mixture is brought to pH 7 with phosphate buffer. The solid which has precipitated out is filtered off with suction, dried and recrystallized from ethyl acetate/diisopropyl ether. 0.45 g (55% of theory) of the title compound is obtained as colorless crystals of m.p. 142°-143° C. (decomp.).
Reaction SMILES: [SH2:1].[CH2:2]([O:4][C:5]([NH:7][CH2:8][C:9]#[N:10])=[O:6])[CH3:3].N1C=CC=CC=1.C(N(CC)CC)C>>[CH2:2]([O:4][C:5]([NH:7][CH2:8][C:9]([NH2:10])=[S:1])=[O:6])[CH3:3]
Reactant: CCOC(=O)NCC#N
Reactant: S
Solvent: c1ccncc1
Solvent: CCN(CC)CC
Product: CCOC(=O)NCC(N)=S
Temperature: 25 °C
Reaction time: 4 h

Procedure:
A stream of H2S is passed into a mixture of 27.5 g of ethoxycarbonylaminoacetonitrile (210 mmol), pyridine (21ml, 210 mmol) and triethylamine (14.5 ml, 105 mmol) according to the procedure of Example 23. After stirring for 4 hours at room temperature and washing with water, a beige precipitate is obtained which is filtered off to give 6.6 g of ethoxycarbonylaminothioacetamide, which is a beige powder melting at 116° C.
Reaction SMILES: [C:1]([C:4]1[CH:5]=[C:6]([N:10]([CH3:20])[S:11]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)(=[O:13])=[O:12])[CH:7]=[CH:8][CH:9]=1)(=[O:3])[CH3:2].CO[CH:23](OC)[N:24]([CH3:26])[CH3:25]>C(OCC)(=O)C.CO>[CH3:23][N:24]([CH3:26])[CH:25]=[CH:2][C:1]([C:4]1[CH:5]=[C:6]([N:10]([CH3:20])[S:11]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)(=[O:13])=[O:12])[CH:7]=[CH:8][CH:9]=1)=[O:3]
Reactant: COC(OC)N(C)C
Reactant: CC(=O)c1cccc(N(C)S(=O)(=O)c2ccccc2)c1
Solvent: CCOC(C)=O
Solvent: CO
Product: CN(C)C=CC(=O)c1cccc(N(C)S(=O)(=O)c2ccccc2)c1
Yield: 84 %

Procedure:
1.25 g (4.32 mmol) of N-(3-acetyl-phenyl)-N-methyl-benzenesulfonamide were dissolved in 10 ml of N,N-dimethylformamide dimethylacetal and the resultant solution was refluxed for 18 hours. The excess of volatile reagent was removed by reduced pressure distillation to yield a crude which was chromatographied over silica gel using a gradient of ethyl acetate/methanol as eluent. 1.25 g of N-[3-[3-(dimethylamino)-1-oxo-2-propenyl]phenyl]-N-methyl-benzenesulfonamide as a yellowish-white solid were obtained (yield 84%).
Reaction SMILES: [C:1]([C:5]1[CH:10]=[CH:9][C:8]([C:11]2[S:15][CH:14]=[C:13]([C:16](=[N:18][NH:19][C:20]([NH:22][C:23]3[CH:32]=[CH:31][C:26]([C:27]([O:29]C)=[O:28])=[C:25]([N+:33]([O-:35])=[O:34])[CH:24]=3)=[S:21])[CH3:17])[C:12]=2[OH:36])=[CH:7][CH:6]=1)([CH3:4])([CH3:3])[CH3:2].[OH-].[Na+].Cl.O>C(O)(C)C>[C:1]([C:5]1[CH:10]=[CH:9][C:8]([C:11]2[S:15][CH:14]=[C:13]([C:16](=[N:18][NH:19][C:20]([NH:22][C:23]3[CH:32]=[CH:31][C:26]([C:27]([OH:29])=[O:28])=[C:25]([N+:33]([O-:35])=[O:34])[CH:24]=3)=[S:21])[CH3:17])[C:12]=2[OH:36])=[CH:7][CH:6]=1)([CH3:2])([CH3:3])[CH3:4]
Reactant: COC(=O)c1ccc(NC(=S)NN=C(C)c2csc(-c3ccc(C(C)(C)C)cc3)c2O)cc1[N+](=O)[O-]
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: CC(C)O
Solvent: O
Product: CC(=NNC(=S)Nc1ccc(C(=O)O)c([N+](=O)[O-])c1)c1csc(-c2ccc(C(C)(C)C)cc2)c1O
Temperature: 25 °C
Reaction time: 8 h
Yield: 61.8 %

Procedure:
Methyl 4-{[(2-{1-[5-(4-t-butylphenyl)-4-hydroxy-3-thienyl]ethylidene}hydrazino)carbonothioyl]amino}-2-nitrobenzoate (95 mg, 0.18 mmol) synthesized in Synthetic Example 92 was dissolved in isopropyl alcohol (1.8 mL), and 0.2 M sodium hydroxide aqueous solution (2.0 mL, 0.40 mmol) was added thereto, followed by stirring overnight at room temperature. After completion of the stirring, 1 M hydrochloric acid (0.40 mL, 0.40 mmol) and water were added thereto, and the precipitated solid was filtered to obtain 57 mg of the desired product as a pale yellow solid (yield 61%).