Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH:1]1[CH:6]=[CH:5][C:4]([CH:7]([NH2:11])[C:8]([NH2:10])=[O:9])=[CH:3][CH:2]=1.[CH2:12]1[CH2:18][S:15](=[O:17])(=[O:16])[O:14][CH2:13]1>O1CCCC1.O1CCOCC1>[NH2:10][C:8](=[O:9])[C@@H:7]([NH:11][CH2:13][CH2:12][CH2:18][S:15]([OH:17])(=[O:16])=[O:14])[C:4]1[CH:3]=[CH:2][CH:1]=[CH:6][CH:5]=1
Reactant: NC(=O)C(N)c1ccccc1
Reactant: O=S1(=O)CCCO1
Solvent: C1COCCO1
Solvent: C1CCOC1
Product: NC(=O)[C@@H](NCCCS(=O)(=O)O)c1ccccc1
Temperature: 25 °C
Yield: 38.9 %

Procedure:
To a solution of D-Phenylglycine amide (850 mg, 7.5 mmol) in tetrahydrofuran (10 mL) and 1,4-dioxane (4 mL) was added 1,3-propanesultone (818 mg, 6.8 mmol). The solution stirred at reflux for 2 hours. The reaction was cooled to room temperature. The solid was collected by filtration and washed with acetone (2×20 mL). The solid was dissolved in 50% water/EtOH mL). Dowex Marathon C ion exchange resin (strongly acidic) was added to the solution. The suspension was stirred for 15 minutes before the resin was removed by filtration. The filtrate was evaporated under reduced pressure. The solid was suspended in acetone (50 mL), filtered and dried in the vacuum oven (50° C.), affording the title compound (720 mg, 34%). 1H NMR (D2O, 500 MHz) δ ppm 7.38 (m, 5H), 4.92, (s, 1H), 3.00 (m, 1H), 2.90 (m, 1H), 2.78 (m, 2H), 1.97 (m, 2H). 13C (D2O, 125 MHz) δ ppm 170.14, 130.95, 130.24, 129.94, 128.74, 63.40, 47.99, 44.92, 21.27. [α]D=+106° (c=0.0016 in water), ES-MS 273 (M+1).
Reaction SMILES: [CH3:1][O:2][C:3]([CH:5]1[N:9]2[C:10](=[O:17])[CH:11]([NH2:16])[CH2:12][CH:13]=[CH:14][CH2:15][CH:8]2[CH2:7][CH2:6]1)=[O:4].[C:18]1([N:24]=[C:25]=[O:26])[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1.C(N(CC)CC)C>C(Cl)Cl>[CH3:1][O:2][C:3]([CH:5]1[N:9]2[C:10](=[O:17])[CH:11]([NH:16][C:25]([NH:24][C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=3)=[O:26])[CH2:12][CH:13]=[CH:14][CH2:15][CH:8]2[CH2:7][CH2:6]1)=[O:4]
Reactant: COC(=O)C1CCC2CC=CCC(N)C(=O)N21
Reactant: O=C=Nc1ccccc1
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: COC(=O)C1CCC2CC=CCC(NC(=O)Nc3ccccc3)C(=O)N21

Procedure:
6-Amino-5-oxo-1,2,3,5,6,7,10,10a-octahydro-pyrrolo[1,2-a]azocine-3-carboxylic acid methyl ester, 8, (120 mg, 0.5 mmol), phenyl isocyanate (110 μL, 1 mmol) and triethyl amine (200 μL) are stirred in CH2Cl2 (10 mL) at room temperature. After complete consumption of starting material, the reaction is poured into 1 N HCl; washed with brine; and dried of sodium sulfate. The organics are evaporated and the residue is purified over silica (40% ethyl acetate: hexane). The desired product is obtained as a clear oil. 1H NMR (CDCl3): δ 7.81 (s, 1H), 7.35 (m, 2H), 7.23 (t, J=7.3 Hz, 2H), 6.98 (t, J=7.4 Hz, 1H), 6.85 (bs, 1H), 5.81 (m, 2H), 5.28 (m, 1H), 4.52 (dd, J=8.9, 2.5 Hz, 1H),4.27 (m, 1H), 3.58 (s, 3H), 2.95–2.82 (m, 2H), 2.45 (m, 1H), 2.29 (m, 1H), 2.16–1.96 (m, 4H). 13C NMR (CDCl3): δ 173.0, 172.4, 155.8, 139.4, 129.1, 129.0, 126.2, 122.8, 119.9, 60.6, 58.9, 52.1, 51.3, 34.9, 33.1, 33.0, 27.5. ESI MS: 358.15 (M+H).
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[S:9][C:10]3[CH:16]=[CH:15][CH:14]=[CH:13][C:11]=3[N:12]=2)=[CH:4][CH:3]=1.[C:17]1([CH3:27])[CH:22]=[CH:21][C:20]([S:23](Cl)(=[O:25])=[O:24])=[CH:19][CH:18]=1.O>N1C=CC=CC=1>[S:9]1[C:10]2[CH:16]=[CH:15][CH:14]=[CH:13][C:11]=2[N:12]=[C:8]1[C:5]1[CH:4]=[CH:3][C:2]([NH:1][S:23]([C:20]2[CH:21]=[CH:22][C:17]([CH3:27])=[CH:18][CH:19]=2)(=[O:25])=[O:24])=[CH:7][CH:6]=1
Reactant: Nc1ccc(-c2nc3ccccc3s2)cc1
Reactant: Cc1ccc(S(=O)(=O)Cl)cc1
Solvent: c1ccncc1
Solvent: O
Product: Cc1ccc(S(=O)(=O)Nc2ccc(-c3nc4ccccc4s3)cc2)cc1

Procedure:
To 2-(4-aminophenyl)benzothiazole (0.5 g, 2.2 mmol) in pyridine (6 mL) is added para-toluenesulphonyl chloride (0.506 g, 2.7 mmol, 1.5 eq.) in pyridine (4 mL). The reaction mixture is heated at reflux for 10 mins, then cooled and water (10 mL) added. The white precipitate formed is collected on a filter, washed with water, and dried under vacuum to give N-[4-(benzothiazol-2-yl)phenyl]-4-methylbenzenesulfonamide as a white solid.
Reaction SMILES: [F:1][C:2]([F:14])([F:13])[C:3]1[CH:4]=[CH:5][C:6]2[S:10][C:9](=[O:11])[NH:8][C:7]=2[CH:12]=1.[Br:15][C:16]1[CH:17]=[N:18][C:19]([C:22]2[CH:27]=[CH:26][CH:25]=[C:24]([CH2:28]Cl)[CH:23]=2)=[N:20][CH:21]=1.O>CN(C=O)C>[Br:15][C:16]1[CH:21]=[N:20][C:19]([C:22]2[CH:23]=[C:24]([CH:25]=[CH:26][CH:27]=2)[CH2:28][N:8]2[C:7]3[CH:12]=[C:3]([C:2]([F:1])([F:13])[F:14])[CH:4]=[CH:5][C:6]=3[S:10][C:9]2=[O:11])=[N:18][CH:17]=1
Reactant: O=c1[nH]c2cc(C(F)(F)F)ccc2s1
Reactant: ClCc1cccc(-c2ncc(Br)cn2)c1
Solvent: CN(C)C=O
Solvent: O
Product: O=c1sc2ccc(C(F)(F)F)cc2n1Cc1cccc(-c2ncc(Br)cn2)c1
Temperature: 80 °C
Reaction time: 3 h

Procedure:
1 g (4.56 mmol) of 5-trifluoromethyl-3H-benzothiazol-2-one, 1.3 g (4.56 mmol) of 5-bromo-2-(3-chloromethylphenyl)pyrimidine and 4.5 g (13.69 mmol) of caesium carbonates are suspended in 15 ml of DMF and stirred at room temperature for 15 h and at 80° C. for 3 h. The suspension is added to water, and the precipitate is filtered off with suction, washed with methanol and dried in vacuo, giving beige crystals; HPLC: Rt.=3.72 min (method A);
Reaction SMILES: [F:1][C:2]1[C:9]([C:10]2[CH:15]=[CH:14][N:13]3[N:16]=[C:17]([C:19]4[CH:24]=[CH:23][C:22]([F:25])=[CH:21][CH:20]=4)[CH:18]=[C:12]3[CH:11]=2)=[CH:8][CH:7]=[C:6]([F:26])[C:3]=1[CH:4]=[O:5].[C:27]([Mg]Br)#[CH:28]>O1CCCC1>[F:1][C:2]1[C:9]([C:10]2[CH:15]=[CH:14][N:13]3[N:16]=[C:17]([C:19]4[CH:24]=[CH:23][C:22]([F:25])=[CH:21][CH:20]=4)[CH:18]=[C:12]3[CH:11]=2)=[CH:8][CH:7]=[C:6]([F:26])[C:3]=1[CH:4]([OH:5])[C:27]#[CH:28]
Reactant: C#C[Mg]Br
Reactant: O=Cc1c(F)ccc(-c2ccn3nc(-c4ccc(F)cc4)cc3c2)c1F
Solvent: C1CCOC1
Product: C#CC(O)c1c(F)ccc(-c2ccn3nc(-c4ccc(F)cc4)cc3c2)c1F
Yield: 58.7 %

Procedure:
The procedure described in stage 2.5 is followed, starting with 0.270 g (0.77 mmol) of 2,6-difluoro-3-[2-(4-fluorophenyl)pyrazolo[1,5-a]pyridin-5-yl]benzaldehyde obtained in stage 6.1, in solution in 15 ml of tetrahydrofuran, followed by addition of 4.60 ml (2.30 mmol) of an ethynylmagnesium bromide solution (0.5M in tetrahydrofuran) and after chromatography on silica gel, elution being carried out with a mixture of cyclohexane and dichloromethane (1/3), 0.171 g (57%) of the expected product is obtained in the form of a pale yellow powder.
Reaction SMILES: [O:1]1[CH2:6][CH2:5][CH:4]([CH2:7][C:8]([OH:10])=O)[CH2:3][CH2:2]1.C(Cl)(=O)C([Cl:14])=O>>[O:1]1[CH2:6][CH2:5][CH:4]([CH2:7][C:8]([Cl:14])=[O:10])[CH2:3][CH2:2]1
Reactant: O=C(Cl)C(=O)Cl
Reactant: O=C(O)CC1CCOCC1
Product: O=C(Cl)CC1CCOCC1

Procedure:
Commercially available (tetrahydro-pyran-4-yl)-acetic acid and oxalyl chloride were processed as described for example 9A to afford the title compound. MS (DCI/NH3) m/z 159 (M+H)+.
Reaction SMILES: C([N-]C(C)C)(C)C.[Li+].[C:9]([O:20][CH3:21])(=[O:19])[CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH3:18].Br[CH2:23][C:24]#[C:25][CH3:26].Cl>O1CCCC1>[CH2:23]([CH:10]([CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH3:18])[C:9]([O:20][CH3:21])=[O:19])[C:24]#[C:25][CH3:26]
Reactant: CC#CCBr
Reactant: CCCCCCCCCC(=O)OC
Agent: CC(C)[N-]C(C)C
Agent: Cl
Agent: [Li+]
Solvent: C1CCOC1
Product: CC#CCC(CCCCCCCC)C(=O)OC
Temperature: -78 °C

Procedure:
A solution of 0.055 mol of lithium diisopropylamide (LDA) in 100 ml tetrahydrofuran (THF) was cooled to −78° C. under an inert atmosphere, and 0.055 mol of methyl decanoate in THF was added dropwise with stirring. The mixture was allowed to warm over one hour to −20° C., then cooled again to −78° C. A solution of 1-bromo-2-butyne (0.050 mol) in THF (20 ml) was added dropwise, and the mixture allowed to warm to room temperature overnight. Aqueous 6N HCl (100 ml) was added, and the product extracted with ethyl ether, dried with anhydrous sodium sulfate, concentrated, and distilled in vacuo to provide methyl 2-(2-butynyl)decanoate as an oil.
Reaction SMILES: [C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([O:14][C:15]2[CH:34]=[CH:33][C:18]([NH:19][CH2:20][C:21]3[CH:30]=[C:29]4[C:24]([CH:25]=[CH:26][C:27]([C:31]#[N:32])=[CH:28]4)=[CH:23][CH:22]=3)=[CH:17][CH:16]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH:35]1([C:41](Cl)=[O:42])[CH2:40][CH2:39][CH2:38][CH2:37][CH2:36]1>>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([O:14][C:15]2[CH:16]=[CH:17][C:18]([N:19]([CH2:20][C:21]3[CH:22]=[CH:23][C:24]4[C:29](=[CH:28][C:27]([C:31]#[N:32])=[CH:26][CH:25]=4)[CH:30]=3)[C:41]([CH:35]3[CH2:40][CH2:39][CH2:38][CH2:37][CH2:36]3)=[O:42])=[CH:33][CH:34]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]
Reactant: CC(C)(C)OC(=O)N1CCC(Oc2ccc(NCc3ccc4ccc(C#N)cc4c3)cc2)CC1
Reactant: O=C(Cl)C1CCCCC1
Product: CC(C)(C)OC(=O)N1CCC(Oc2ccc(N(Cc3ccc4ccc(C#N)cc4c3)C(=O)C3CCCCC3)cc2)CC1

Procedure:
Starting compound: 7-[[4-[(1-t-butoxycarbonyl-4-piperidyl)oxy]anilino]methyl]-2-naphthalenecarbonitrile, cyclohexanecarbonyl chloride.
Reaction SMILES: C(O[C:4]1[C:13]2[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=2)[CH2:7][CH2:6][N:5]=1)C.[ClH:14].[NH2:15][NH2:16]>C(O)C>[ClH:14].[NH:15]([C:4]1[C:13]2[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=2)[CH2:7][CH2:6][N:5]=1)[NH2:16]
Reactant: NN
Reactant: CCOC1=NCCc2ccccc21
Agent: Cl
Solvent: CCO
Product: NNC1=NCCc2ccccc21
Yield: 79.8 %

Procedure:
A mixture of 1-ethoxy-3,4-dihydroisoquinoline (1.0 g.), hydrazine monohydrochloride (0.4 g.) and absolute ethanol (15 ml.) was heated under reflux (for 40 min.). The solution was cooled, filtered and concentrated and the residue was recrystallized from ethanol-ether, affording 1-hydrazino-3,4-dihydroisoquinoline hydrochloride (0.9 g., m.p. 205°-207° C.). C. A mixture of 1-hydrazino-3,4-dihydroisoquinoline (8.0 g.), acetaldehyde (20 ml.) and ethanol (20 ml.) was allowed to stand at room temperature (for 45 min). Ethanolic sulfuric acid was added until the solution was distinctly acidic. Ether was added. The resulting oil crystallized and the crystals were recrystallized from ethanol-ether, affording 1-(2-ethylidenehydrazino)-3,4-dihydroisoquinoline (I: X=CH3, X'=Y=Y'=Z=Z'=H) sulfate in two crops (8.3 g., m.p. 152°-154° C.; 0.5 g., m.p. 152°-155° C.).
Reaction SMILES: [Cl:1][C:2]1[C:3]([OH:9])=[CH:4][C:5](=[O:8])[NH:6][CH:7]=1.[C:10]1([C:20](Cl)=[O:21])[C:19]2[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=2)[CH:13]=[CH:12][CH:11]=1>N1C=CC=CC=1>[Cl:1][C:2]1[C:3]([O:9][C:20]([C:10]2[C:19]3[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=3)[CH:13]=[CH:12][CH:11]=2)=[O:21])=[CH:4][C:5](=[O:8])[NH:6][CH:7]=1
Reactant: O=c1cc(O)c(Cl)c[nH]1
Reactant: O=C(Cl)c1cccc2ccccc12
Solvent: c1ccncc1
Product: O=C(Oc1cc(=O)[nH]cc1Cl)c1cccc2ccccc12
Yield: 27.9 %

Procedure:
The general procedure of Example 45 was followed using 2.00 g 5-chloro-4-hydroxy-2-pyridone, 3.93 g of α-naphthoyl chloride and 100 ml of pyridine, thereby producing 1.15 g of the title compound in a yield of 28%.
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[CH:6][C:5]([C:8](=[O:29])[CH2:9][N:10]2[C:14](=[O:15])[C:13]([C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=3)([C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=3)[N:12]=[C:11]2[CH3:28])=[CH:4][CH:3]=1.[CH3:30][O:31][C:32]1[CH:40]=[CH:39][CH:38]=[CH:37][C:33]=1[C:34](Cl)=[O:35]>>[CH3:30][O:31][C:32]1[CH:40]=[CH:39][CH:38]=[CH:37][C:33]=1[C:34]([NH:1][C:2]1[CH:3]=[CH:4][C:5]([C:8](=[O:29])[CH2:9][N:10]2[C:14](=[O:15])[C:13]([C:22]3[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=3)([C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=3)[N:12]=[C:11]2[CH3:28])=[CH:6][CH:7]=1)=[O:35]
Reactant: COc1ccccc1C(=O)Cl
Reactant: CC1=NC(c2ccccc2)(c2ccccc2)C(=O)N1CC(=O)c1ccc(N)cc1
Product: COc1ccccc1C(=O)Nc1ccc(C(=O)CN2C(=O)C(c3ccccc3)(c3ccccc3)N=C2C)cc1

Procedure:
Synthesis in analogy to Example 8 starting from 3-[2-(4-amino-phenyl)-2-oxo-ethyl]-2-methyl-5,5-diphenyl-3,5-dihydro-imidazol-4-one and 2-methoxy-benzoyl chloride to yield 2-methoxy-N-{4-[2-(2-methyl-5-oxo-4,4-diphenyl-4,5-dihydro-imidazol-1-yl)-acetyl]-phenyl}-benzamide. LC/MS at 254 nm; [M+H] 518; Rt 3.772 min.
Reaction SMILES: [CH:1]1([N:7]2[CH2:12][CH2:11][NH:10][CH2:9][CH2:8]2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.C(N(CC)CC)C.[CH2:20]=[C:21]1[O:25][C:23](=[O:24])[CH2:22]1>O1CCCC1>[CH:1]1([N:7]2[CH2:12][CH2:11][N:10]([C:23](=[O:24])[CH2:22][C:21](=[O:25])[CH3:20])[CH2:9][CH2:8]2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1
Reactant: C=C1CC(=O)O1
Reactant: C1CCC(N2CCNCC2)CC1
Solvent: C1CCOC1
Solvent: CCN(CC)CC
Product: CC(=O)CC(=O)N1CCN(C2CCCCC2)CC1
Temperature: 25 °C
Reaction time: 2 h

Procedure:
24 g (0.1 mol) of 1-cyclohexylpiperazine are suspended in 150 ml of absolute tetrahydrofuran. 20 ml of triethylamine are poured in and, after 20 minutes, 18.6 g of diketene in 20 ml of tetrahydrofuran are added dropwise, and the mixture is then stirred at room temperature for 2 h. Thereafter part of the solvent is removed by distillation in vacuo, the mixture is poured onto 200 ml of ice-water, 20 g of Na2CO3 are added, and extraction is carried out 3 times with 50 ml of methylene chloride each time. After the organic phase has been dried with MgSO4, crude 3-oxo-butyric acid 4-cyclohexylpiperazide is obtained as the residue from evaporation.
Reaction SMILES: [O:1]=[C:2]1[C:14]2[C:13]3[C:12]([C:15]([O:17][CH3:18])=[O:16])=[CH:11][CH:10]=[CH:9][C:8]=3[NH:7][C:6]=2[CH2:5][NH:4][CH2:3]1.Cl.Cl[CH2:21][CH2:22][N:23]([CH3:25])[CH3:24].C([O-])([O-])=O.[K+].[K+]>CN(C=O)C.C(Cl)Cl>[CH3:24][N:23]([CH3:25])[CH2:22][CH2:21][N:4]1[CH2:3][C:2](=[O:1])[C:14]2[C:13]3[C:12]([C:15]([O:17][CH3:18])=[O:16])=[CH:11][CH:10]=[CH:9][C:8]=3[NH:7][C:6]=2[CH2:5]1
Reactant: COC(=O)c1cccc2[nH]c3c(c12)C(=O)CNC3
Reactant: CN(C)CCCl
Agent: Cl
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: ClCCl
Product: COC(=O)c1cccc2[nH]c3c(c12)C(=O)CN(CCN(C)C)C3
Temperature: 50 °C
Yield: 38.1 %

Procedure:
Methyl 4-oxo-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole-5-carboxylate (183 mg, 0.75 mol) was dissolved in DMF (20 ml) and 2-chloro-N,N-dimethylethanamine hydrochloride (107 mg, 0.75 mmol), and K2CO3 (207 mg, 1.5 mmol) were subsequently added. The reaction was stirred at 50° C. until the starting material was disappeared. The reaction mixture was then diluted with CH2Cl2 (15 ml) and washed with water three times. The organic layer was dried with MgSO4. Evaporation of most of the solvent and the crude product was purified by chromatography column on silica gel (elution with CH2Cl2/MeOH/NH3.H2O) to provide 0.09 g of methyl 2-(2-(dimethylamino)ethyl)-4-oxo-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole-5-carboxylate. MS (ESI) m/e [M+1]+ 316.
Reaction SMILES: C[Si]([N-][Si](C)(C)C)(C)C.[K+].C([O:18][C:19](=[O:52])[N:20]([CH2:43][CH:44](O)[C:45]1[CH:50]=[CH:49][CH:48]=[CH:47][N:46]=1)[CH2:21][C:22]1[CH:27]=[C:26]([C:28]([F:31])([F:30])[F:29])[CH:25]=[CH:24][C:23]=1[C:32]1[CH:37]=[C:36]([CH:38]([CH3:40])[CH3:39])[CH:35]=[CH:34][C:33]=1[O:41][CH3:42])C1C=CC=CC=1>C1(C)C=CC=CC=1.C1COCC1>[CH:38]([C:36]1[CH:35]=[CH:34][C:33]([O:41][CH3:42])=[C:32]([C:23]2[CH:24]=[CH:25][C:26]([C:28]([F:30])([F:29])[F:31])=[CH:27][C:22]=2[CH2:21][N:20]2[CH2:43][CH:44]([C:45]3[CH:50]=[CH:49][CH:48]=[CH:47][N:46]=3)[O:18][C:19]2=[O:52])[CH:37]=1)([CH3:40])[CH3:39]
Reactant: COc1ccc(C(C)C)cc1-c1ccc(C(F)(F)F)cc1CN(CC(O)c1ccccn1)C(=O)OCc1ccccc1
Agent: C[Si](C)(C)[N-][Si](C)(C)C
Agent: [K+]
Solvent: C1CCOC1
Solvent: Cc1ccccc1
Product: COc1ccc(C(C)C)cc1-c1ccc(C(F)(F)F)cc1CN1CC(c2ccccn2)OC1=O
Temperature: 25 °C
Reaction time: 1 h

Procedure:
A solution of potassium bis(trimethylsilyl)amide (464 μL of a 0.5M solution in toluene, 0.232 mmol) was added dropwise to a stirred solution of benzyl(2-hydroxy-2-pyridin-2-ylethyl){[5′-isopropyl-2′-methoxy-4-(trifluoromethyl)biphenyl-2-yl]methyl}carbamate (134.3 mg, 0.232 mmol) in dry THF (10 mL) at room temperature under N2. After stirring at room temperature for 1 h, the reaction was quenched with saturated NH4Cl (10 mL) and extracted with EtOAc (3×20 mL). The combined extracts were dried (Na2SO4) and concentrated in vacuo to give the crude product. This was purified by flash chromatography (Si, 25×160 mm, 0-70% EtOAc in hexanes gradient) to afford 3-{[5′-isopropyl-2′-methoxy-4-(trifluoromethyl)biphenyl-2-yl]methyl}-5-pyridin-2-yl-1,3-oxazolidin-2-one. Rf=0.58 (50% EtOAc/hexanes). LCMS calc.=471.19; found=471.2 (M+1)+.
Reaction SMILES: [CH2:1]([C:3]1([CH3:20])[C:7](=[O:8])[C:6](I)=[C:5]([C:10]2[CH:15]=[CH:14][C:13]([S:16]([CH3:19])(=[O:18])=[O:17])=[CH:12][CH:11]=2)[O:4]1)[CH3:2].C(=O)([O-])[O-].[Na+].[Na+].[C:27]([C:30]1[CH:35]=[CH:34][C:33](B(O)O)=[CH:32][CH:31]=1)(=[O:29])[CH3:28]>C1(C)C=CC=CC=1.C(O)C.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[C:27]([C:30]1[CH:35]=[CH:34][C:33]([C:6]2[C:7](=[O:8])[C:3]([CH2:1][CH3:2])([CH3:20])[O:4][C:5]=2[C:10]2[CH:15]=[CH:14][C:13]([S:16]([CH3:19])(=[O:18])=[O:17])=[CH:12][CH:11]=2)=[CH:32][CH:31]=1)(=[O:29])[CH3:28]
Reactant: CCC1(C)OC(c2ccc(S(C)(=O)=O)cc2)=C(I)C1=O
Reactant: CC(=O)c1ccc(B(O)O)cc1
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: Cc1ccccc1
Solvent: CCO
Product: CCC1(C)OC(c2ccc(S(C)(=O)=O)cc2)=C(c2ccc(C(C)=O)cc2)C1=O
Temperature: 95 °C
Reaction time: 12 h
Yield: 61.2 %

Procedure:
To a stirred solution of 2-ethyl-4-iodo-2-methy-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone (200 mg) in 15 ml toluene and 5 ml ethanol, were added 34 mg of tetrakis(triphenylphosphine)palladium(0), 5 ml of 2M aqueous sodium carbonate solution and 120 mg of 4-acetylbenzeneboronic acid. Then the reaction solution was stirred at 95° C. for 12 hours. The reaction solvent was evaporated off under reduced pressure and the resulting residue was extracted with 50 ml water and dichloromethane (30 ml×3). Then the organic layer was concentrated in vacuo and the resulting crude product was purified by column chromatography (hexane/ethylacetate) to afford 120 mg of 4-(4-acetylphenyl)-2-ethyl-2-methyl-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone as a solid. mp: 147-148° C. NMR: δ0.97 (t, J=7.5 Hz, 3H), 1.56 (s, 3H), 1.99 (m, 2H), 2.62 (s, 3H), 3.08 (s, 3H), 7.39 (d, J=8.7 Hz, 2H), 7.83 (d, J=8.7 Hz, 2H), 7.97 (m, 2H). IR (cm−1): 2929, 1684, 1410, 1317, 1149, 1016, 769, 552.
Reaction SMILES: [CH2:1]([SH:19])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH3:18].[N+:20]([C:23]1[CH:28]=[CH:27][C:26]([N:29]=[C:30]=[O:31])=[CH:25][CH:24]=1)([O-:22])=[O:21].N1C=CC=CC=1>C(#N)C>[N+:20]([C:23]1[CH:24]=[CH:25][C:26]([NH:29][C:30](=[O:31])[S:19][CH2:1][CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH3:18])=[CH:27][CH:28]=1)([O-:22])=[O:21]
Reactant: CCCCCCCCCCCCCCCCCCS
Reactant: O=C=Nc1ccc([N+](=O)[O-])cc1
Solvent: c1ccncc1
Solvent: CC#N
Product: CCCCCCCCCCCCCCCCCCSC(=O)Nc1ccc([N+](=O)[O-])cc1
Temperature: 25 °C
Reaction time: 0.17 h
Yield: 99.1 %

Procedure:
In a three necked flask equipped with a dropping funnel, a thermometer and a reflux condenser, n-octadecanethiol (183 g) was dissolved in acetonitrile (1000 ml) in a nitrogen atmosphere. To the solution, p-nitrophenyl isocyanate (100 g) was gradually added, and then pyridine (4 ml) was added dropwise, the mixture was stirred at room temperature for 10 minutes and then heat-refluxed for 30 minutes. When the reaction mixture was cooled to room temperature, crystals precipitated. The crystals were collected by filtering and washed with acetonitrile. S-n-octadecyl p-nitrophenylthiocarbamate (272 g) was obtained at a yield of 99%.
Reaction SMILES: [NH2:1][C@H:2]1[CH2:7][CH2:6][C@H:5]([NH:8][C:9]([C:11]2[C:15]3[N:16]=[CH:17][N:18]=[C:19]([C:20]4[CH:25]=[C:24]([F:26])[C:23]([O:27][CH3:28])=[CH:22][C:21]=4[O:29][CH2:30][CH:31]4[CH2:33][CH2:32]4)[C:14]=3[NH:13][CH:12]=2)=[O:10])[CH2:4][CH2:3]1.[C:34](Cl)(=[O:36])[CH3:35]>>[C:34]([NH:1][C@H:2]1[CH2:7][CH2:6][C@H:5]([NH:8][C:9]([C:11]2[C:15]3[N:16]=[CH:17][N:18]=[C:19]([C:20]4[CH:25]=[C:24]([F:26])[C:23]([O:27][CH3:28])=[CH:22][C:21]=4[O:29][CH2:30][CH:31]4[CH2:33][CH2:32]4)[C:14]=3[NH:13][CH:12]=2)=[O:10])[CH2:4][CH2:3]1)(=[O:36])[CH3:35]
Reactant: COc1cc(OCC2CC2)c(-c2ncnc3c(C(=O)N[C@H]4CC[C@H](N)CC4)c[nH]c23)cc1F
Reactant: CC(=O)Cl
Product: COc1cc(OCC2CC2)c(-c2ncnc3c(C(=O)N[C@H]4CC[C@H](NC(C)=O)CC4)c[nH]c23)cc1F

Procedure:
Starting from trans-4-(2-cyclopropylmethoxy-5-fluoro-4-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-7-carboxylic acid (4-amino-cyclohexyl)-amide (example A139) and acetyl chloride the title compound is obtained as colorless solid.
Reaction SMILES: [N+:1]([C:4]1[CH:9]=[CH:8][C:7]([CH2:10][CH2:11][N:12]2[CH2:17][CH2:16][CH:15]([NH:18][C:19](=[O:26])[C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=3)[CH2:14][CH2:13]2)=[CH:6][CH:5]=1)([O-])=O>[Pt]=O>[NH2:1][C:4]1[CH:9]=[CH:8][C:7]([CH2:10][CH2:11][N:12]2[CH2:13][CH2:14][CH:15]([NH:18][C:19](=[O:26])[C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=3)[CH2:16][CH2:17]2)=[CH:6][CH:5]=1
Reactant: O=C(NC1CCN(CCc2ccc([N+](=O)[O-])cc2)CC1)c1ccccc1
Agent: O=[Pt]
Product: Nc1ccc(CCN2CCC(NC(=O)c3ccccc3)CC2)cc1
Reaction time: 3 h

Procedure:
1-[2-(p-Nitrophenyl)ethyl]-4-benzamidopiperidine (3.0 g.) was hydrogenated in absolute alcohol (400 ml.) at 50 p.s.i. and 20° C for 3 hours inthe presence of 300 mg. of platinum oxide as catalyst. The catalyst was filtered off and the solution evaporated to give the crude product as a foam. Crystallisation from a mixture of benzene and n-hexane gave the title compound, m.p. 193°-195° C. (Found: C, 74.4; H, 7.9; N, 12.9. C20H25N3O requires C, 74.3; H, 7.8; N, 13.0%).
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([Cl:8])[C:3]=1[CH2:9][S:10]([C:13]1[CH:14]=[C:15]2[C:19](=[CH:20][CH:21]=1)[NH:18][C:17](=[O:22])[CH2:16]2)(=[O:12])=[O:11].[CH:23]1([CH2:26][N:27]2[CH2:32][CH2:31][N:30]([CH2:33][C:34]3[C:35]([CH3:42])=[C:36]([CH:40]=O)[NH:37][C:38]=3[CH3:39])[CH2:29][CH2:28]2)[CH2:25][CH2:24]1>C(O)C.N1CCCCC1>[CH:23]1([CH2:26][N:27]2[CH2:32][CH2:31][N:30]([CH2:33][C:34]3[C:35]([CH3:42])=[C:36](/[CH:40]=[C:16]4\[C:17](=[O:22])[NH:18][C:19]5[C:15]\4=[CH:14][C:13]([S:10]([CH2:9][C:3]4[C:2]([Cl:1])=[CH:7][CH:6]=[CH:5][C:4]=4[Cl:8])(=[O:12])=[O:11])=[CH:21][CH:20]=5)[NH:37][C:38]=3[CH3:39])[CH2:29][CH2:28]2)[CH2:25][CH2:24]1
Reactant: Cc1[nH]c(C=O)c(C)c1CN1CCN(CC2CC2)CC1
Reactant: O=C1Cc2cc(S(=O)(=O)Cc3c(Cl)cccc3Cl)ccc2N1
Solvent: CCO
Solvent: C1CCNCC1
Product: Cc1[nH]c(/C=C2\C(=O)Nc3ccc(S(=O)(=O)Cc4c(Cl)cccc4Cl)cc32)c(C)c1CN1CCN(CC2CC2)CC1

Procedure:
5-(2,6-Dichloro-phenylmethanesulfonyl)-1,3-dihydro-indol-2-one was condensed with 4-(4-cyclopropylmethyl-piperazin-1-ylmethyl)-3,5-dimethyl-1H-pyrrole-2-carbaldehyde in ethanol and piperidine to give the titled compound. MS m/z 613 [M−1].
Reaction SMILES: Br[CH2:2][C:3]([C:5]1[CH:10]=[C:9]([N+:11]([O-:13])=[O:12])[C:8]([OH:14])=[C:7]([OH:15])[CH:6]=1)=O.[NH2:16][C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][N:18]=1>C(O)C>[N:16]1[CH:2]=[C:3]([C:5]2[CH:6]=[C:7]([OH:15])[C:8]([OH:14])=[C:9]([N+:11]([O-:13])=[O:12])[CH:10]=2)[N:18]2[CH:19]=[CH:20][CH:21]=[CH:22][C:17]=12
Reactant: Nc1ccccn1
Reactant: O=C(CBr)c1cc(O)c(O)c([N+](=O)[O-])c1
Solvent: CCO
Product: O=[N+]([O-])c1cc(-c2cnc3ccccn23)cc(O)c1O
Temperature: 25 °C

Procedure:
A mixture of 987.5 mg of 2-bromo-3',4'-dihydroxy-5'-nitroacetophenone and 1.01 g of 2-aminopyridine is melted at 110°. After 30 minutes the melt is treated with 15 ml of ethanol and heated to boiling under reflux for 3 hours. The reaction mixture is then cooled to room temperature and the crystals are removed by filtration under suction. There is obtained 5-(imidazo[1,2-a]pyridin-3-yl)-3-nitropyrocatechol of m.p. 250°14 252° (from N,N-dimethylformamide/methanol).