Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: C([C:9]1([O:18][CH2:17][C@:15]([C:19](=[O:26])[C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)([OH:16])[C@:13]([C:27](=[O:34])[C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)([OH:14])[C@@:11]1([C:35](=[O:42])[C:36]1[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=1)[OH:12])[OH:10])(=O)C1C=CC=CC=1.[BrH:43].C(O)(=O)C.ClCCl>O>[Br:43][C:9]1([O:18][CH2:17][C@:15]([C:19](=[O:26])[C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)([OH:16])[C@:13]([C:27](=[O:34])[C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)([OH:14])[C@@:11]1([C:35](=[O:42])[C:36]1[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=1)[OH:12])[OH:10]
Reactant: O=C(c1ccccc1)C1(O)OC[C@@](O)(C(=O)c2ccccc2)[C@@](O)(C(=O)c2ccccc2)[C@]1(O)C(=O)c1ccccc1
Reactant: Br
Solvent: ClCCl
Solvent: CC(=O)O
Solvent: O
Product: O=C(c1ccccc1)[C@]1(O)[C@](O)(C(=O)c2ccccc2)COC(O)(Br)[C@@]1(O)C(=O)c1ccccc1
Temperature: 10 °C
Reaction time: 6 h
Yield: 70 %

Procedure:
While the internal temperature of the reactor containing 2.946 kg (5.20 mol) of 1,2,3,4-tetrabenzoyl-L-arabinopyranose was maintained at 0-20° C., 4.21 kg of a 30-33% hydrogen bromide/acetic acid solution was added dropwise thereto, and the mixture was stirred at room temperature for 6 hours. After completion of the reaction, 1.296 liters of dichloromethane was added to the reaction solution, which was then stirred for 30 minutes. Next, the solution was added dropwise to a reactor containing 4.162 liters of purified water, and was stirred for 30 minutes, and then separated into layers. The water layer was back-extracted with 1.296 liters of dichloromethane. The oil layer was washed two times with 0.195 kg of aqueous saturated sodium chloride solution and one time with 0.248 kg of aqueous saturated sodium bicarbonate solution, and then dried with sodium sulfate, and the solvent was removed by concentration. To the concentrated residue, 1.30 liters of dichloromethane was added, the solution was stirred for 2-3 hours, and 6.50 liters of hexane was added thereto. The resulting solution was cooled to 0-5° C., stirred for 3-4 hours, and then filtered. The filtered solids were washed with 2.76 liters of hexane and dried in a vacuum, thus obtaining 1.912 kg (70% yield) of 1-bromo-2,3,4-tribenzoyl-L-arabinopyranose. 1H NMR (CDCl3): δ 8.20˜7.90 (dd, 4H), 7.90˜7.80 (d, 2H), 7.70˜7.20 (m, 9H), 6.93 (d, 1H), 5.97 (dd, 1H), 5.82 (m, 1H), 5.70 (dd, 1H), 4.50 (d, 1H), 4.25 (d, 1H).
Reaction SMILES: [CH2:1]([C:8]1[C:9](=O)[NH:10][CH:11]=[CH:12][CH:13]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.P12(SP3(SP(SP(S3)(S1)=S)(=S)S2)=S)=[S:16]>N1C=CC=CC=1.[Cl-].[Na+].O>[CH2:1]([C:8]1[C:9]([SH:16])=[N:10][CH:11]=[CH:12][CH:13]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: S=P12SP3(=S)SP(=S)(S1)SP(=S)(S2)S3
Reactant: O=c1[nH]cccc1Cc1ccccc1
Agent: [Cl-]
Agent: [Na+]
Solvent: O
Solvent: c1ccncc1
Product: Sc1ncccc1Cc1ccccc1
Reaction time: 8 h
Yield: 16.7 %

Procedure:
3-Benzyl-2-pyridone (1.65g, 8.9 mmol) and P2S5 (1.98 g, 8.9 mmol) were heated at reflux for 22 hours under argon in pyridine (17ml), and then allowed to stand overnight at ambient temperature. The mixture was diluted with brine and extracted with ethyl acetate. The ethyl acetate extracts were dried (MgSO4) and purified by chromatography using 5% CH3OH--CH2Cl2 as eluant followed by recrystallization from CH2Cl2 --ether--hexane to yield 300 mg (15%) of 3-benzyl-2-mercaptopyridine: m.p. 129°-130° C. That the 3-benzyl isomer had been isolated was confirmed by use of proton NMR spectroscopy.
Reaction SMILES: [CH3:1][C:2]1([CH3:17])[CH2:11][CH2:10][C:9]([CH3:13])([CH3:12])[C:8]2[CH:7]=[C:6]([CH:14]3[CH2:16][O:15]3)[CH:5]=[CH:4][C:3]1=2.[NH2:18][C:19]1[CH:29]=[CH:28][C:22]([C:23]([O:25][CH2:26][CH3:27])=[O:24])=[CH:21][CH:20]=1>C1(C)C=CC=CC=1>[C:23]([C:22]1[CH:21]=[CH:20][C:19]([NH:18][CH2:16][CH:14]([C:6]2[CH:5]=[CH:4][C:3]3[C:2]([CH3:17])([CH3:1])[CH2:11][CH2:10][C:9]([CH3:12])([CH3:13])[C:8]=3[CH:7]=2)[OH:15])=[CH:29][CH:28]=1)([O:25][CH2:26][CH3:27])=[O:24]
Reactant: CC1(C)CCC(C)(C)c2cc(C3CO3)ccc21
Reactant: CCOC(=O)c1ccc(N)cc1
Solvent: Cc1ccccc1
Product: CCOC(=O)c1ccc(NCC(O)c2ccc3c(c2)C(C)(C)CCC3(C)C)cc1
Yield: 30.9 %

Procedure:
26 g (110 millimoles) of (5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthalenyl)-oxirane, 15 g (90 millimoles) of ethyl 4-aminobenzoate, 135 g of basic alumina and 450 ml of toluene were refluxed for 2 hours. The solid was then filtered off and the filtrate was evaporated down. After recrystallization from n-heptane with a little ethyl acetate, the residue gave 11.0 g of N-(4-carbethoxyphenyl)-1-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthalenyl)-2-aminoethanol. The structure was determined by H-NMR spectroscopy.
Reaction SMILES: Br[C:2]1[N:7]=[N:6][C:5]([NH2:8])=[N:4][CH:3]=1.[Br-].[Si:10]([O:17][CH2:18][C:19]1[S:23][C:22]([Zn+])=[N:21][CH:20]=1)([C:13]([CH3:16])([CH3:15])[CH3:14])([CH3:12])[CH3:11]>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.C1COCC1>[Si:10]([O:17][CH2:18][C:19]1[S:23][C:22]([C:2]2[N:7]=[N:6][C:5]([NH2:8])=[N:4][CH:3]=2)=[N:21][CH:20]=1)([C:13]([CH3:16])([CH3:14])[CH3:15])([CH3:11])[CH3:12]
Reactant: Nc1ncc(Br)nn1
Reactant: CC(C)(C)[Si](C)(C)OCc1cnc([Zn+])s1
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: [Br-]
Solvent: C1CCOC1
Product: CC(C)(C)[Si](C)(C)OCc1cnc(-c2cnc(N)nn2)s1
Temperature: 80 °C

Procedure:
In a separate flask was added 6-bromo-1,2,4-triazin-3-amine (10.0 g, 57.5 mmol), (PPh3)4Pd (12.1 g, 11.5 mmol), and THF (200 mL). The mixture was heated to 80° C., followed by the dropwise addition (1 h) of (5-((tert-butyldimethylsilyloxy)methyl)thiazol-2-yl)zinc(II) bromide prepared in the step above. The reaction was then cooled to rt, filtered through a silica pad, concentrated, and then purified using silica gel chromatography to afford 6.7 g the title compound as a light yellow solid.
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[CH:6][C:5]([CH3:8])=[CH:4][CH:3]=1.[C:9](Cl)(=[O:18])[CH:10]=[CH:11]C1C=CC=CC=1>>[CH3:8][C:5]1[CH:4]=[C:3]2[C:2](=[CH:7][CH:6]=1)[NH:1][C:9](=[O:18])[CH:10]=[CH:11]2
Reactant: O=C(Cl)C=Cc1ccccc1
Reactant: Cc1ccc(N)cc1
Product: Cc1ccc2[nH]c(=O)ccc2c1

Procedure:
The title compound is prepared from p-toluidine and cinnamoyl chloride according to the procedure described in Synthesis 1975, 739. The crude product obtained is triturated in Et2O/hexanes and filtered to give the title compound as a beige solid. 1H NMR (DMSO-d6, 300 MHz) δ11.60 (bs, 1H), 7.82 (d, 1H), 7.41 (s, 1H), 7.30 (d, 1H), 7.18 (d, 1H), 6.45 (d, 1H), 2.30 (s, 3H).
Reaction SMILES: C(Cl)(=O)C(Cl)=O.CS(C)=O.[CH2:11]([N:18]([CH3:26])[C@H:19]([CH2:24][OH:25])[C@H:20]([CH2:22][CH3:23])[CH3:21])[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1.C(N(CC)CC)C>ClCCl>[CH2:11]([N:18]([CH3:26])[C@@H:19]([C@@H:20]([CH3:21])[CH2:22][CH3:23])[CH:24]=[O:25])[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1
Reactant: CC[C@H](C)[C@@H](CO)N(C)Cc1ccccc1
Agent: O=C(Cl)C(=O)Cl
Solvent: CS(C)=O
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: CC[C@H](C)[C@@H](C=O)N(C)Cc1ccccc1
Temperature: 25 °C
Reaction time: 0.25 h
Yield: 100.2 %

Procedure:
To a stirred solution of 36 ml oxalyl chloride (0.42 mol; Fluka) in 1100 ml dichloromethane were added at −70° C. a solution of 44 ml dimethyl sulfoxide (0.62 mol) in 800 ml dichloromethane over 0.5 h. After stirring at −700 for 15 min a solution of 77.5 g N-benzyl-N-methyl-isoleucinol (0.35 mol) in 700 ml dichloromethane was added at −70° C. over ˜0.5 h and stirring was continued for 15 min. After the addition of 234 ml triethylamine (1.68 mol) at −65° C. stirring was continued for 5 min and the white suspension stirred at −50° C. for 1 h. The dry ice-bath was removed and 3000 ml deionized water was added drop wise and under stirring while the reaction mixture was warmed up to RT. The organic layer was washed twice with 2000 ml 10% brine and the organic layer was dried (Na2SO4). Removal of the solvent by rotary evaporation (40° C./≧10 mbar/0.1 mbar, 2 h) yielded 76.9 g (100.2%) yellow oily product which was used without purification in the next step.
Reaction SMILES: [NH2:1][CH2:2][CH2:3][CH2:4][CH2:5][NH:6][C:7](=[O:13])[O:8][C:9]([CH3:12])([CH3:11])[CH3:10].[Cl:14][C:15]1[C:20]([N+:21]([O-:23])=[O:22])=[C:19](Cl)[C:18]([CH3:25])=[C:17]([CH3:26])[N:16]=1.C(N(CC)CC)C>CN(C)C=O>[Cl:14][C:15]1[C:20]([N+:21]([O-:23])=[O:22])=[C:19]([NH:1][CH2:2][CH2:3][CH2:4][CH2:5][NH:6][C:7](=[O:13])[O:8][C:9]([CH3:10])([CH3:12])[CH3:11])[C:18]([CH3:25])=[C:17]([CH3:26])[N:16]=1
Reactant: CC(C)(C)OC(=O)NCCCCN
Reactant: Cc1nc(Cl)c([N+](=O)[O-])c(Cl)c1C
Solvent: CN(C)C=O
Solvent: CCN(CC)CC
Product: Cc1nc(Cl)c([N+](=O)[O-])c(NCCCCNC(=O)OC(C)(C)C)c1C
Reaction time: 8 h
Yield: 48 %

Procedure:
A solution of tert-butyl 4-aminobutylcarbamate (8.52 g, 45.24 mmol) in N,N-dimethylformamide was added to a solution of 2,4-dichloro-5,6-dimethyl-3-nitropyridine (10.00 g, 45.24 mmol) and triethylamine (12.6 mL, 90.5 mmol) in N,N-dimethylformamide (320 mL). The reaction mixture was stirred overnight and then concentrated under reduced pressure. The residue was partitioned between water and ethyl acetate. The layers were separated and the aqueous layer was extracted with ethyl acetate. The organics were combined, washed with brine and then concentrated under reduced pressure to provide a brown oily residue. This material was purified by flash chromatography (400 mL silica gel, eluting initially with 10% ethyl acetate in hexane and then increasing the gradient to 15% and then to 25%) to provide 8.1 g of tert-butyl 4-[(2-chloro-5,6-dimethyl-3-nitropyridin-4-yl)amino]butylcarbamate as a yellow solid.
Reaction SMILES: [NH2:1][C@@H:2]1[CH2:7][C:6]2[C:8]([O:13][CH3:14])=[CH:9][CH:10]=[C:11]([F:12])[C:5]=2[O:4][CH2:3]1.[CH3:15][C:16]([CH3:18])=O.C([BH3-])#N.[Na+].C(O)(=O)C>CO>[F:12][C:11]1[C:5]2[O:4][CH2:3][C@H:2]([NH:1][CH:16]([CH3:18])[CH3:15])[CH2:7][C:6]=2[C:8]([O:13][CH3:14])=[CH:9][CH:10]=1
Reactant: COc1ccc(F)c2c1C[C@@H](N)CO2
Reactant: CC(C)=O
Agent: [BH3-]C#N
Agent: [Na+]
Solvent: CO
Solvent: CC(=O)O
Product: COc1ccc(F)c2c1C[C@@H](NC(C)C)CO2
Temperature: 25 °C
Reaction time: 8 h

Procedure:
(R)-3-Amino-8-fluoro-5-methoxy-3,4-dihydro-2H-1-benzopyran (1.62 g, 8.21 mmol) was dissolved in anhydrous methanol (20 mL) and to this was acetone (6.0 mL, 82.1 mmol) added. The reaction was cooled (ice-bath) then sodium cyanoborohydride (0.92 g, 14.8 mmol) was added, the pH was adjusted to 4-5 with acetic acid and the reaction was allowed to stir at room temperature overnight. The solvent was removed in vacuo, the remains were taken into a 2M solution of NH3 and then extracted thrice with diethyl ether. The combined ether portions were dried (MgSO4), filtered, and the solvent removed in vacuo to give the crude residue that was used as is in the next reaction. GC-MS (70 eV) M=239 (81%).
Reaction SMILES: C1(S(Cl)(=O)=O)C=CC=CC=1.[CH2:11]([O:14][C@H:15]1[CH2:20][CH2:19][C@H:18]([C:21]2[CH:22]=[N:23][C:24]([C:27]3[CH:35]=[CH:34][C:30]([C:31]([NH2:33])=O)=[CH:29][CH:28]=3)=[N:25][CH:26]=2)[CH2:17][CH2:16]1)[CH2:12][CH3:13].N1C=CC=CC=1.Cl>C(Cl)Cl>[CH2:11]([O:14][C@H:15]1[CH2:20][CH2:19][C@H:18]([C:21]2[CH:22]=[N:23][C:24]([C:27]3[CH:28]=[CH:29][C:30]([C:31]#[N:33])=[CH:34][CH:35]=3)=[N:25][CH:26]=2)[CH2:17][CH2:16]1)[CH2:12][CH3:13]
Reactant: CCCO[C@H]1CC[C@H](c2cnc(-c3ccc(C(N)=O)cc3)nc2)CC1
Agent: Cl
Agent: O=S(=O)(Cl)c1ccccc1
Solvent: c1ccncc1
Solvent: ClCCl
Product: CCCO[C@H]1CC[C@H](c2cnc(-c3ccc(C#N)cc3)nc2)CC1
Temperature: 40 °C

Procedure:
9.2 Ml. of benzenesulfonyl chloride are added dropwise while stirring to a suspension of 16.0 g. of trans-p-[5-(4-n-propyloxycyclohexyl)-2-pyrimidinyl]benzamide in 170 ml. of pyridine. The mixture is then warmed to 40° C. for 15 hours in an oil-bath. The clear mixture is poured into a mixture of 200 g. of ice and 24.1 ml. of concentrated hydrochloric acid and the product is taken up in methylene chloride. The extract is washed three times with 195 ml. of 3-N hydrochloric acid each time, then with 100 ml. of saturated sodium bicarbonate solution and with water, dried over sodium sulfate and evaporated. The crude product is chromatographed on a column of 200 g. of silica gel with benzene and with benzene containing 1% and 2% acetone (v/v). The fractions which are pure according to thin-layer chromatography are recrystallized from acetone/hexane. There is obtained trans-p-[5-(4-n-propyloxycyclohexyl)-2-pyrimidinyl]benzonitrile; melting point 114.5° C., clearing point 223.5° C.
Reaction SMILES: [CH3:1][C:2]([CH3:31])([CH3:30])[C:3]#[C:4][C:5]1[S:9][C:8]([C:10]([OH:12])=[O:11])=[C:7]([N:13]([C@H:23]2[CH2:28][CH2:27][C@H:26]([OH:29])[CH2:25][CH2:24]2)[C:14]([C@H:16]2[CH2:21][CH2:20][C@H:19]([CH3:22])[CH2:18][CH2:17]2)=[O:15])[CH:6]=1.[H-].[Na+].[Cl:34][C:35]1[N:40]=[C:39](Cl)[CH:38]=[CH:37][N:36]=1.C(OCC)(=O)C>CN(C=O)C>[CH3:31][C:2]([CH3:30])([CH3:1])[C:3]#[C:4][C:5]1[S:9][C:8]([C:10]([OH:12])=[O:11])=[C:7]([N:13]([C:14]([C@H:16]2[CH2:21][CH2:20][C@H:19]([CH3:22])[CH2:18][CH2:17]2)=[O:15])[C@H:23]2[CH2:28][CH2:27][C@H:26]([O:29][C:37]3[CH:38]=[CH:39][N:40]=[C:35]([Cl:34])[N:36]=3)[CH2:25][CH2:24]2)[CH:6]=1
Reactant: CC(C)(C)C#Cc1cc(N(C(=O)[C@H]2CC[C@H](C)CC2)[C@H]2CC[C@H](O)CC2)c(C(=O)O)s1
Reactant: Clc1ccnc(Cl)n1
Agent: [H-]
Agent: [Na+]
Solvent: CCOC(C)=O
Solvent: CN(C)C=O
Product: CC(C)(C)C#Cc1cc(N(C(=O)[C@H]2CC[C@H](C)CC2)[C@H]2CC[C@H](Oc3ccnc(Cl)n3)CC2)c(C(=O)O)s1
Reaction time: 0.5 h

Procedure:
5-(3,3-Dimethyl-but-1-ynyl)-3-[(trans-4-hydroxy-cyclohexyl)-(trans-4-methyl-cyclohexanecarbonyl)-amino]-thiophene-2-carboxylic acid (211 mg, 0.46 mmol) in DMF (2 mL) at 0 deg C. was treated with sodium hydride (110 mg, 2.8 mmol, 60% oil dispersion) in portions. The mixture was stirred for 30 minutes at 0 deg C. and a solution of 2,4-dichloropyrimidine (210 mg, 1.4 mmol) in DMF (1 mL) was added dropwise. The reaction mixture was allowed to warm and stir at room temperature. After completion, ethyl acetate (2-3 mL) was added and the mixture was carefully quenched with citric acid (10% aqueous solution, 2-3 mL). Water was added and the mixture was extracted with ethyl acetate (2×30 mL). The combined organic layers were dried over magnesium sulfate, filtered and concentrated. The residue was passed through a plug of silica (0-5% MeOH:DCM eluent) and concentrated to yield 162 mg of 5-(3,3-dimethyl-but-1-ynyl)-3-{(trans-4-methyl-cyclohexanecarbonyl)-[trans-4-(2-chloro-pyrimidin-4-yloxy)-cyclohexyl]-amino}-thiophene-2-carboxylic acid as an impure black oil which was carried on without further purification.
Reaction SMILES: [F:1][C:2]1[C:7]([NH:8][NH2:9])=[CH:6][CH:5]=[CH:4][N:3]=1.C(=O)([O-])[O-].[Na+].[Na+].[C:16](OCC)(=[O:24])[C:17]#[C:18][C:19]([O:21][CH2:22][CH3:23])=[O:20].Cl>C(O)C>[F:1][C:2]1[C:7]([N:8]2[C:16]([OH:24])=[CH:17][C:18]([C:19]([O:21][CH2:22][CH3:23])=[O:20])=[N:9]2)=[CH:6][CH:5]=[CH:4][N:3]=1
Reactant: NNc1cccnc1F
Reactant: CCOC(=O)C#CC(=O)OCC
Agent: Cl
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: CCO
Product: CCOC(=O)c1cc(O)n(-c2cccnc2F)n1
Temperature: 25 °C
Yield: 33.7 %

Procedure:
To a solution of 2-fluoro-3-hydrazinopyridine (30.0 g) in ethanol (472 mL) were added sodium carbonate (65.2 g) and diethyl but-2-ynedioate (40.2 g). After refluxing for 18 hr, the mixture was cooled to room temperature, treated with 2 mol/L hydrochloric acid, and extracted twice with ethyl acetate. The extract was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was suspended in diethyl ether, and the obtained solid was collected by filtration and dried under reduced pressure to give the title compound as a yellow solid (yield 20.0 g, yield 34%).
Reaction SMILES: C([O:3][C:4](=O)[C:5]([C:21]#[N:22])=[C:6]1[C:14]2[C:9](=[CH:10][C:11]([O:17][CH3:18])=[C:12]([O:15][CH3:16])[CH:13]=2)[C:8]([CH3:20])([CH3:19])[CH2:7]1)C.[C:24]([CH2:26][C:27](NCC#C)=O)#[N:25].N1CCCC1.C(O)(=O)C1C=CC=CC=1>C1(C)C=CC=CC=1.O>[C:21]([C:5](=[C:6]1[C:14]2[C:9](=[CH:10][C:11]([O:17][CH3:18])=[C:12]([O:15][CH3:16])[CH:13]=2)[C:8]([CH3:20])([CH3:19])[CH2:7]1)[C:4]([NH:25][CH2:24][C:26]#[CH:27])=[O:3])#[N:22]
Reactant: C#CCNC(=O)CC#N
Reactant: CCOC(=O)C(C#N)=C1CC(C)(C)c2cc(OC)c(OC)cc21
Agent: O=C(O)c1ccccc1
Solvent: Cc1ccccc1
Solvent: O
Solvent: C1CCNC1
Product: C#CCNC(=O)C(C#N)=C1CC(C)(C)c2cc(OC)c(OC)cc21
Yield: 49.9 %

Procedure:
A 50 ml reaction flask equipped with a water separator and a reflux condenser was charged with 2.2 g of 2,3-dihydro-5,6-dimethoxy-3,3-dimethyl-1H-inden-1-one (see Example 1), 1.2 g of 2-cyano-N-prop-2-ynyl-acetamide (see above), catalytic amounts of pyrrolidine, and benzoic acid in 20 ml of toluene. The reaction mixture was refluxed for 24 hours with simultaneous separation of water. Then, the product in the cold reaction mixture was filtered off and recrystallized in ethylacetate to yield 1.13 g of white crystals, m.p. 202° C.-205° C. UV 362 nm (ε=24′992). Solubility: 0.04% in CÉTIOL LC
Reaction SMILES: [H-].[Na+].[N:3]1[CH:8]=[CH:7][CH:6]=[C:5]([NH2:9])[CH:4]=1.Cl[C:11]1[C:12]([NH2:33])=[N:13][CH:14]=[C:15]([C:17]2[CH:22]=[C:21]([S:23]([N:26]3[CH2:31][CH2:30][O:29][CH2:28][CH2:27]3)(=[O:25])=[O:24])[CH:20]=[CH:19][C:18]=2[CH3:32])[N:16]=1>C1COCC1>[CH3:32][C:18]1[CH:19]=[CH:20][C:21]([S:23]([N:26]2[CH2:31][CH2:30][O:29][CH2:28][CH2:27]2)(=[O:25])=[O:24])=[CH:22][C:17]=1[C:15]1[N:16]=[C:11]([NH:9][C:5]2[CH:4]=[N:3][CH:8]=[CH:7][CH:6]=2)[C:12]([NH2:33])=[N:13][CH:14]=1
Reactant: Nc1cccnc1
Reactant: Cc1ccc(S(=O)(=O)N2CCOCC2)cc1-c1cnc(N)c(Cl)n1
Agent: [H-]
Agent: [Na+]
Solvent: C1CCOC1
Product: Cc1ccc(S(=O)(=O)N2CCOCC2)cc1-c1cnc(N)c(Nc2cccnc2)n1

Procedure:
A suspension of NaH (60% dispersion in oil) (12 mg, 0.298 mmol) is stirred in THF (3 ml). Pyridine-3-ylamine (28 mg, 0.293 mmol) is added and gas evolved. Once all gas production is stopped 3-Chloro-5-[2-methyl-5-(morpholine-4-sulfonyl)-phenyl]-pyrazin-2-ylamine (Intermediate M) (100 mg, 0.271 mmol) in THF (3 ml) is added. The reaction mixture is microwaved at 120° C. for 10 minutes. More NaH (60%) (33 mg, 0.813 mmol) is added to the reaction mixture and the sample is microwaved at 120° C. for 40 minutes. The reaction is quenched with water (100 ml) and evaporated to dryness in vacuo. The brown residue is purified by reverse phase column chromatography to yield the title compound as a brown glass. 1H NMR (400 MHz, DMSO-6) δ 9.14 (1H, d), 8.99 (1H, s), 8.38-8.33 (3H, m), 7.81 (1H, s), 7.70 (1H, d), 7.66-7.60 (5H, m), 3.64 (4H, t), 2.88 (4H, t), 2.54 (3H, s); MS m/z 427 [M+H]+
Reaction SMILES: Br[C:2]1[CH:3]=[C:4]([C:14]([O:16][CH3:17])=[O:15])[N:5]([C:7]2[C:12]([Cl:13])=[CH:11][CH:10]=[CH:9][N:8]=2)[CH:6]=1.[CH2:18]([O:20]C([Sn](CCCC)(CCCC)CCCC)=C)[CH3:19].[Cl-].[Li+]>C1COCC1.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:18]([C:2]1[CH:3]=[C:4]([C:14]([O:16][CH3:17])=[O:15])[N:5]([C:7]2[C:12]([Cl:13])=[CH:11][CH:10]=[CH:9][N:8]=2)[CH:6]=1)(=[O:20])[CH3:19]
Reactant: C=C(OCC)[Sn](CCCC)(CCCC)CCCC
Reactant: COC(=O)c1cc(Br)cn1-c1ncccc1Cl
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: [Cl-]
Agent: [Li+]
Solvent: C1CCOC1
Product: COC(=O)c1cc(C(C)=O)cn1-c1ncccc1Cl

Procedure:
Under argon, 5.0 g (15.6 mmol) of methyl 4-bromo-1-(3-chloropyridin-2-yl)-1H-pyrrole-2-carboxylate were dissolved in THF, and 8.2 g (21.9 mmol) of (1-ethoxyvinyl)tributylstannane, 2.1 g of lithium chloride and 0.9 g (0.8 mmol) of tetrakis(triphenylphosphine)palladium were added at room temperature and the mixture was stirred under reflux for 48 h. The solvent was then distilled off, and the residue was taken up in 200 ml of THF and stirred in the presence of 12 ml of 2N hydrochloric acid at RT for a further 24 h. Once more, the solvent was distilled off, and the residue was dissolved in 120 ml of methyl tert-butyl ether and, at RT, stirred vigorously with 120 ml of saturated potassium fluoride solution for 1 h. The organic phase was separated off and concentrated. The desired product was isolated by chromatographic purification.
Reaction SMILES: CO[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[S:9][CH2:10][CH2:11][CH2:12][N:13]([C@H:29]1[CH2:34][CH2:33][C@H:32]([CH3:35])[CH2:31][CH2:30]1)[C:14](=[O:28])[NH:15][C:16]1[S:17][C:18]([S:21][C:22]([CH3:27])([CH3:26])[C:23]([OH:25])=[O:24])=[CH:19][N:20]=1.[CH2:36]([O:38]C(=O)C(SC1SC(N)=NC=1)(C)C)C.COC1C=CC(S)=CC=1>>[CH3:36][O:38][C:7]1[CH:6]=[CH:5][C:4]([S:9][CH2:10][CH2:11][CH2:12][N:13]([C@H:29]2[CH2:30][CH2:31][C@H:32]([CH3:35])[CH2:33][CH2:34]2)[C:14](=[O:28])[NH:15][C:16]2[S:17][C:18]([S:21][C:22]([CH3:26])([CH3:27])[C:23]([OH:25])=[O:24])=[CH:19][N:20]=2)=[CH:3][CH:8]=1
Reactant: CCOC(=O)C(C)(C)Sc1cnc(N)s1
Reactant: COc1ccccc1SCCCN(C(=O)Nc1ncc(SC(C)(C)C(=O)O)s1)[C@H]1CC[C@H](C)CC1
Agent: COc1ccc(S)cc1
Product: COc1ccc(SCCCN(C(=O)Nc2ncc(SC(C)(C)C(=O)O)s2)[C@H]2CC[C@H](C)CC2)cc1

Procedure:
The compound was prepared following an analogous procedure to the one described for the synthesis 2-{2-[3-[3-(2-methoxy-phenylsulfanyl)-propyl]-3-(trans-4-methyl-cyclohexyl)-ureido]-thiazol-5-ylsulfanyl}-2-methyl-propionic acid using 2-(2-amino-thiazol-5-ylsulfanyl)-2-methyl-propionic acid ethyl ester and 4-methoxy-thiophenol.
Reaction SMILES: [CH2:1]([O:3][C:4](=[O:13])[C:5]1[CH:10]=[CH:9][CH:8]=[C:7]([CH:11]=O)[CH:6]=1)[CH3:2].[C:14]1([CH2:20][C:21]([OH:23])=[O:22])[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1.C(N(CC)CC)C.O>C(OC(=O)C)(=O)C>[CH2:1]([O:3][C:4](=[O:13])[C:5]1[CH:10]=[CH:9][CH:8]=[C:7]([CH:11]=[C:20]([C:21]([OH:23])=[O:22])[C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[CH:6]=1)[CH3:2]
Reactant: CCOC(=O)c1cccc(C=O)c1
Reactant: O=C(O)Cc1ccccc1
Solvent: CCN(CC)CC
Solvent: O
Solvent: CC(=O)OC(C)=O
Product: CCOC(=O)c1cccc(C=C(C(=O)O)c2ccccc2)c1
Yield: 438.7 %

Procedure:
17.8 g (0.01 mol) of 3-formyl-benzoic acid ethyl ester, 13.6 g (0.1 mol) of phenylacetic acid and 10 g of triethylamine were dissolved in 30 ml of acetic anhydride and the solution was heated to the reflux for 5 hours. After cooling, 300 ml of water were added to the reaction mixture and the mixture was then heated to the boil for 20 minutes. The solid residue was then decanted off hot, and this was recrystallised from methanol, to which a little water had been added. 13 g (43.9% of theory) of 3-(2-carboxy-2-phenylvinyl)-benzoic acid ethyl ester were obtained as light yellow crystals of melting point 139°-140° C. (isomer mixture with a cis proportion of about 90%). ##STR60##