Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: C(N1C=CN=C1)(N1C=CN=C1)=O.[CH:13]1([C:18]([C:20]2[CH:21]=[C:22]([C@@H:26]([CH3:30])[C:27](O)=[O:28])[CH:23]=[CH:24][CH:25]=2)=[O:19])[CH2:17][CH2:16][CH2:15][CH2:14]1.[CH3:31][S:32]([NH2:35])(=[O:34])=[O:33].C1CCN2C(=NCCC2)CC1>C(Cl)Cl>[CH:13]1([C:18]([C:20]2[CH:21]=[C:22]([C@@H:26]([CH3:30])[C:27]([NH:35][S:32]([CH3:31])(=[O:34])=[O:33])=[O:28])[CH:23]=[CH:24][CH:25]=2)=[O:19])[CH2:17][CH2:16][CH2:15][CH2:14]1
Reactant: CS(N)(=O)=O
Reactant: C[C@@H](C(=O)O)c1cccc(C(=O)C2CCCC2)c1
Agent: O=C(n1ccnc1)n1ccnc1
Solvent: ClCCl
Solvent: C1CCC2=NCCCN2CC1
Product: C[C@@H](C(=O)NS(C)(=O)=O)c1cccc(C(=O)C2CCCC2)c1
Temperature: 25 °C
Reaction time: 1.5 h
Yield: 790 %

Procedure:
1,1′-Carbonyldiimidazole (0.5 g, 3.06 mmol) was added to a solution of (R)-2-[3-cyclopentanoyl)phenyl]propionic acid (II) (0.68 g, 2.78 mmol) in dry CH2Cl2 (8 mL) and the resulting mixture was left stirring at room temperature for 90 min. Methanesulfonamide (0.26 g, 2.78 mmol) and DBU (0.43 mL, 2.78 mmol) were added and the mixture was left stirring fur further 16 h at room temperature. The organic phase was washed with 0.5N HCl (2×10 mL), with 5% NaH2PO4 (3×10 mL) and with water (2×10 mL). After drying with Na2SO4, solvent was removed under vacuum and the crude was purified by flash chromatography (eluent mixture CH2Cl2/MeOH 95:5). Pure N—[(R)-2-(3-cyclopentanecarbonylphenyl)propionyl]methanesulfonamide 22 was isolated as colourless oil (0.67 g, 2.09 mmol). Yield 790%.
Reaction SMILES: [N:1]([CH2:4][CH2:5][O:6][CH3:7])=[C:2]=[S:3].[CH3:8][N:9]([CH2:11][C:12]1[O:16][C:15]([CH2:17][S:18][CH2:19][CH2:20][NH2:21])=[CH:14][CH:13]=1)[CH3:10]>C(#N)C>[CH3:10][N:9]([CH2:11][C:12]1[O:16][C:15]([CH2:17][S:18][CH2:19][CH2:20][NH:21][C:2]([NH:1][CH2:4][CH2:5][O:6][CH3:7])=[S:3])=[CH:14][CH:13]=1)[CH3:8]
Reactant: CN(C)Cc1ccc(CSCCN)o1
Reactant: COCCN=C=S
Solvent: CC#N
Product: COCCNC(=S)NCCSCc1ccc(CN(C)C)o1

Procedure:
1-(Isothiocyanato)-2-methoxyethane (1.17 g) and 2-[[[5-(dimethylamino)methyl-2-furanyl]methyl]thio]ethanamine (2.14 g) in acetonitrile were stood overnight. Solvent was removed and the residual oil chromatographed (silica/methanol) to give N-[2-[[[5-(dimethylamino)methyl-2-furanyl]methyl]thio]ethyl]-N'-(2-methoxyethyl)thiourea as a pale oil Rf 0.45. Analysis Found: C, 50.64; H, 7.51; N, 12.58. C14H25N3O2S2 requires: C, 50.75; H, 7.55; N, 12.69%.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([N:10]([CH2:17][CH:18]2[CH2:20][CH2:19]2)[CH:11]([CH2:15][CH3:16])[C:12]([OH:14])=O)[CH:5]=[CH:6][C:7]=1[C:8]#[N:9].[CH2:21]([NH2:23])[CH3:22]>>[Cl:1][C:2]1[CH:3]=[C:4]([N:10]([CH2:17][CH:18]2[CH2:20][CH2:19]2)[CH:11]([CH2:15][CH3:16])[C:12]([NH:23][CH2:21][CH3:22])=[O:14])[CH:5]=[CH:6][C:7]=1[C:8]#[N:9]
Reactant: CCN
Reactant: CCC(C(=O)O)N(CC1CC1)c1ccc(C#N)c(Cl)c1
Product: CCNC(=O)C(CC)N(CC1CC1)c1ccc(C#N)c(Cl)c1

Procedure:
Synthesized in a manner similar to example 3 using 2-[(3-chloro-4-cyanophenyl)(cyclopropylmethyl)amino]butanoic acid and ethylamine: MS (ES) m/z 320 (M+1).
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[C:6]([N+:8]([O-:10])=[O:9])[C:5](Cl)=[CH:4][C:3]=1[Br:12].C([O-])(O)=O.[Na+:17].[NH2:18][CH2:19][C:20]([OH:22])=[O:21]>CN(C=O)C.O>[Na+:17].[Br:12][C:3]1[C:2]([Cl:1])=[CH:7][C:6]([N+:8]([O-:10])=[O:9])=[C:5]([NH:18][CH2:19][C:20]([O-:22])=[O:21])[CH:4]=1
Reactant: NCC(=O)O
Reactant: O=[N+]([O-])c1cc(Cl)c(Br)cc1Cl
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: O
Product: O=C([O-])CNc1cc(Br)c(Cl)cc1[N+](=O)[O-]
Temperature: 65 °C
Reaction time: 65 h

Procedure:
To a stirred solution of 2,5-dichloro-4-nitrobromobenzene (1.000 g, 3.691 mmol, as prepared above) in DMF (10.0 mL) at 65° C., was added, dropwise, a solution of NaHCO3 (0.316 g, 3.76 mmol) and glycine (0.280 g, 3.73 mmol, Aldrich, used as received) in water (3.8 mL). The resulting suspension was stirred at 65° C. for 65 h. The bright orange suspension was then cooled to room temperature, filtered, washed with water (1.0 mL), and dried under vacuum to afford 0.284 g (98%, based on recovered starting material) of the pure (1H NMR) title compound as an orange powder, m.p. 264-265° C. (decomposed); 1H NMR (DMSO-d6): δ 3.451 (d, 2H, J=3.9 Hz), 7.199 (s, 1H), 8.130 (s, 1H), 8.793 (t, 1H, J=3.6 Hz). It was used as such for the next reaction.
Reaction SMILES: C(Cl)(Cl)Cl.[C:5]([C:7]1[C:8](=[C:15]([C:18]#[N:19])[C:16]#[N:17])[O:9][C:10]([CH3:14])([CH3:13])[C:11]=1[CH3:12])#[N:6].[C:20]([SiH2:24][O:25][C:26]([CH3:52])([CH3:51])[CH:27]1[CH2:32][O:31][C:30]2=[C:33]([CH:38]=[CH:39][C:40]3[CH:45]=[CH:44][C:43]([N:46]([CH2:49][CH3:50])[CH2:47][CH3:48])=[CH:42][CH:41]=3)[S:34][C:35]([CH:36]=O)=[C:29]2[O:28]1)([CH3:23])([CH3:22])[CH3:21]>C(N(CC)CC)C>[C:20]([SiH2:24][O:25][C:26]([CH3:51])([CH3:52])[CH:27]1[CH2:32][O:31][C:30]2=[C:33]([CH:38]=[CH:39][C:40]3[CH:41]=[CH:42][C:43]([N:46]([CH2:49][CH3:50])[CH2:47][CH3:48])=[CH:44][CH:45]=3)[S:34][C:35]([CH:36]=[CH:12][C:11]3[C:10]([CH3:13])([CH3:14])[O:9][C:8](=[C:15]([C:16]#[N:17])[C:18]#[N:19])[C:7]=3[C:5]#[N:6])=[C:29]2[O:28]1)([CH3:23])([CH3:22])[CH3:21]
Reactant: CCN(CC)c1ccc(C=Cc2sc(C=O)c3c2OCC(C(C)(C)O[SiH2]C(C)(C)C)O3)cc1
Reactant: CC1=C(C#N)C(=C(C#N)C#N)OC1(C)C
Solvent: ClC(Cl)Cl
Solvent: CCN(CC)CC
Product: CCN(CC)c1ccc(C=Cc2sc(C=CC3=C(C#N)C(=C(C#N)C#N)OC3(C)C)c3c2OCC(C(C)(C)O[SiH2]C(C)(C)C)O3)cc1
Temperature: 25 °C
Reaction time: 12 h

Procedure:
20 mL of anhydrous chloroform was added to 0.318 g (0.0016 mole) of 2-(3-cyano-4,5,5-trimethyl-5H-furan-2-ylidene)-malononitrile, and 0.640 g (0.00131 mole) of 5. Once in solution, 10 mg of triethylamine were added and the reaction mixture was stirred at room temperature for 12 h. The solvent was removed under reduced pressure. The compound was purified on a silica column with a hexane/ethyl acetate mobile phase.
Reaction SMILES: Br[C:2]1[N:3]=[CH:4][N:5]([C:7]([C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=2)[CH:6]=1.[C:26]([C:28]1[CH:29]=[C:30](B(O)O)[CH:31]=[CH:32][CH:33]=1)#[N:27].COCCOC.C(=O)([O-])[O-].[Na+].[Na+]>ClCCl.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:26]([C:28]1[CH:33]=[C:32]([C:2]2[N:3]=[CH:4][N:5]([C:7]([C:8]3[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=3)([C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=3)[C:20]3[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=3)[CH:6]=2)[CH:31]=[CH:30][CH:29]=1)#[N:27]
Reactant: Brc1cn(C(c2ccccc2)(c2ccccc2)c2ccccc2)cn1
Reactant: N#Cc1cccc(B(O)O)c1
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: ClCCl
Solvent: COCCOC
Product: N#Cc1cccc(-c2cn(C(c3ccccc3)(c3ccccc3)c3ccccc3)cn2)c1
Temperature: 120 °C
Yield: 33.4 %

Procedure:
A mixture of 4-bromo-1-trityl-1H-imidazole (0.2 g, 0.51 mmol), 3-cyanophenylboronic acid (0.11 g, 0.77 mmol), and Pd(PPh3)4 (0.06 g, 0.05 mmol) in a solution of ethylene glycol dimethyl ether (2 mL) and 2M sodium carbonate (2 mL) was heated in a sealed vial overnight at 120° C. After cooling, the reaction mixture was diluted with dichloromethane (30 mL) and washed with water (50 mL) and brine (30 mL). The organic phase was dried over anhydrous sodium sulfate, filtered and concentrated in vacuo. Silica gel chromatography of the crude residue using 2% ethyl acetate in hexanes afforded 0.07 g (34%) 4-(3-cyanophenyl)-1-trityl-1H-imidazole as white foam.
Reaction SMILES: [H-].[Na+].[CH2:3]([O:5][PH:6]([C:8]([O:13][CH2:14][CH3:15])([O:10][CH2:11][CH3:12])[CH3:9])=[O:7])[CH3:4].Br[CH2:17][CH:18]1[CH2:23][CH2:22][CH2:21][CH2:20][CH2:19]1.O>O1CCCC1>[CH2:3]([O:5][P:6]([C:8]([O:13][CH2:14][CH3:15])([O:10][CH2:11][CH3:12])[CH3:9])([CH2:17][CH:18]1[CH2:23][CH2:22][CH2:21][CH2:20][CH2:19]1)=[O:7])[CH3:4]
Reactant: CCO[PH](=O)C(C)(OCC)OCC
Reactant: BrCC1CCCCC1
Agent: [H-]
Agent: [Na+]
Solvent: C1CCOC1
Solvent: O
Product: CCOC(C)(OCC)P(=O)(CC1CCCCC1)OCC
Temperature: 25 °C
Reaction time: 1.5 h

Procedure:
21 g of 99% sodium hydride are suspended at room temperature under argon in 1000 ml of anhydrous tetrahydrofuran, and a solution of 172.2 g of 1,1-diethoxyethylphosphinic acid ethyl ester is added dropwise over a period of 2.5 hours, the temperature being maintained at from 20° to 25°. The reaction is exothermic and involves the evolution of gas. The batch is then stirred for 1.5 hours at room temperature, 142.2 g of bromomethylcyclohexane are added and heating under reflux is effected for 24 hours. The suspension is cooled to 4° and 250 rnl of water are carefully added. Two phases are formed. The tetrahydrofuran phase is separated off and the aqueous phase is extracted twice with 250 ml of dichloromethane each time. Concentration by evaporation yields a brown oil which, after distillation under reduced pressure, gives 1,1-diethoxyethyl(cyclohexylmethyl)phosphinic acid ethyl ester having a boiling point of 95° (1.8×10-4 mbar).
Reaction SMILES: [NH2:1][C:2]1[C:3]([C:8]#[N:9])=[N:4][CH:5]=[CH:6][N:7]=1.[Cl:10][C:11]1[CH:21]=[CH:20][C:14]([O:15][CH2:16][C:17](N)=[NH:18])=[CH:13][CH:12]=1.CN(C)C=O>C(O)C>[NH2:9][C:8]1[C:3]2[C:2](=[N:7][CH:6]=[CH:5][N:4]=2)[N:1]=[C:17]([CH2:16][O:15][C:14]2[CH:20]=[CH:21][C:11]([Cl:10])=[CH:12][CH:13]=2)[N:18]=1
Reactant: N#Cc1nccnc1N
Reactant: N=C(N)COc1ccc(Cl)cc1
Solvent: CN(C)C=O
Solvent: CCO
Product: Nc1nc(COc2ccc(Cl)cc2)nc2nccnc12

Procedure:
Obtained using the procedure described in section c of Example 2, starting with 10.7 g (0.089 mole) of 3-amino-2-pyrazinecarbonitrile and 24.5 g (0.133 mole) of 2-(4-chlorophenoxy)acetamidine [prepared according to C. Djerassi and C. R. Scholz, U.S. Pat. No. 2,517,468; C.A. 1951, 45, 661f] in 320 ml of absolute ethanol. Refluxing time: 7 hours. Yld: 21.5 g (84%), m.p. 246°-248° C. (N,N-dimethylformamide).
Reaction SMILES: Cl.[CH2:2]([C:9]1[CH2:10][C:11]2[C:16]([C:17]=1[CH2:18][CH2:19][NH2:20])=[CH:15][C:14]([O:21][CH3:22])=[CH:13][CH:12]=2)[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.[C:23](Cl)(=[O:26])[CH2:24][CH3:25]>>[CH2:2]([C:9]1[CH2:10][C:11]2[C:16]([C:17]=1[CH2:18][CH2:19][NH:20][C:23](=[O:26])[CH2:24][CH3:25])=[CH:15][C:14]([O:21][CH3:22])=[CH:13][CH:12]=2)[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1
Reactant: CCC(=O)Cl
Reactant: COc1ccc2c(c1)C(CCN)=C(Cc1ccccc1)C2
Agent: Cl
Product: CCC(=O)NCCC1=C(Cc2ccccc2)Cc2ccc(OC)cc21

Procedure:
Starting with 2-(2-benzyl-5-methoxy-1H-inden-3-yl)ethylamine hydrochloride and propionyl chloride, the title compound was synthesized in otherwise the same manner as Example 8 (yield 98%).
Reaction SMILES: F[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[N+:8]([O-:10])=[O:9].[CH3:11][N:12]1[CH2:17][CH2:16][N:15]([CH2:18][CH2:19][CH2:20][NH2:21])[CH2:14][CH2:13]1.C(N(C(C)C)CC)(C)C>O1CCOCC1>[CH3:11][N:12]1[CH2:17][CH2:16][N:15]([CH2:18][CH2:19][CH2:20][NH:21][C:6]2[CH:5]=[CH:4][C:3]([N+:8]([O-:10])=[O:9])=[CH:2][CH:7]=2)[CH2:14][CH2:13]1
Reactant: CN1CCN(CCCN)CC1
Reactant: O=[N+]([O-])c1ccccc1F
Solvent: CCN(C(C)C)C(C)C
Solvent: C1COCCO1
Product: CN1CCN(CCCNc2ccc([N+](=O)[O-])cc2)CC1
Temperature: 25 °C
Reaction time: 48 h
Yield: 74 %

Procedure:
A 100 mL round bottom flask was dried in an oven overnight and cooled to room temperature under Ar(g). The flask was charged with fluoronitrobenzene (0.187 mL, 1.77 mmol), 3-(4-Methyl-piperazin-1-yl)-propylamine (0.361 g, 2.30 mmol) and dioxane (9.0 mL). To the resulting solution diisopropyl ethyl amine (0.463 mL, 2.66 mmol) was added dropwise and allowed to stir at 105° C. for 48 h. The mixture was extracted with EtOAc (3×˜30 mL), and with brine (2×˜30 mL). The combined organic layers were then dried over anhydrous Na2SO4, filtered and concentrated in vacuo. The crude mixture was then purified over silica (10% MeOH/90% CHCl3) affording a yellow solid (0.365 g, 1.31 mmol, 74% yield).
Reaction SMILES: Cl.[CH3:2][N:3]([CH3:7])[CH2:4][CH2:5][SH:6].[H-].[Na+].Br[C:11]1[S:15][C:14]([CH:16]=[O:17])=[CH:13][CH:12]=1>CS(C)=O>[CH3:2][N:3]([CH3:7])[CH2:4][CH2:5][S:6][C:11]1[S:15][C:14]([CH:16]=[O:17])=[CH:13][CH:12]=1
Reactant: CN(C)CCS
Reactant: O=Cc1ccc(Br)s1
Agent: Cl
Agent: [H-]
Agent: [Na+]
Solvent: CS(C)=O
Product: CN(C)CCSc1ccc(C=O)s1
Temperature: 90 °C

Procedure:
2-dimethylaminoethanethiol hydrochloride (1.85 g, 13.09 mmol) was suspended in dry DMSO and sodium hydride (60% dispersed in mineral oil, 1.10 g, 2.1 equivs) was added carefully. The reaction mixture was left stirring for 1 hour before 5-bromo-2-thiophenecarboxaldehyde (2.5 g, 1.56 ml, 13.09 mmol) was added. The reaction mixture was then heated to 90° C. under nitrogen.
Reaction SMILES: [S:1]1[CH:5]=[CH:4][CH:3]=[C:2]1[Li].C1COCC1.[P:12](Cl)([O:17][CH2:18][CH3:19])([O:14][CH2:15][CH3:16])=[O:13]>>[CH2:15]([O:14][P:12]([C:2]1[S:1][CH:5]=[CH:4][CH:3]=1)([O:17][CH2:18][CH3:19])=[O:13])[CH3:16]
Reactant: CCOP(=O)(Cl)OCC
Reactant: [Li]c1cccs1
Solvent: C1CCOC1
Product: CCOP(=O)(OCC)c1cccs1
Temperature: 25 °C

Procedure:
A solution of 2-thienyllithium in THF (1 mmol) was added to a solution of diethyl chlorophosphate (1 mmol) at −78° C. under nitrogen. After 2 h the reaction was warmed to room temperature and quenched with brine. Extraction and chromatography afforded 2-diethylphosphonothiophene as a yellow oil. TLC: Rf=0.37, 50% EtOAc-hexane.
Reaction SMILES: [N+:1]([C:4]1[CH:5]=[C:6]2[CH:12]=[CH:11][NH:10][C:7]2=[N:8][CH:9]=1)([O-:3])=[O:2].C(=O)([O-])[O-].[K+].[K+].Br[CH2:20][C:21]([O:23][C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1)=[O:22]>CN(C=O)C.C(Cl)Cl>[N+:1]([C:4]1[CH:5]=[C:6]2[CH:12]=[CH:11][N:10]([CH2:20][C:21]([O:23][C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=3)=[O:22])[C:7]2=[N:8][CH:9]=1)([O-:3])=[O:2]
Reactant: O=C(CBr)Oc1ccccc1
Reactant: O=[N+]([O-])c1cnc2[nH]ccc2c1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: ClCCl
Product: O=C(Cn1ccc2cc([N+](=O)[O-])cnc21)Oc1ccccc1
Temperature: 25 °C
Reaction time: 20 h
Yield: 13.7 %

Procedure:
To a solution of 5-nitro-1H-pyrrolo[2,3-b]pyridine (0.200 g, 1.226 mmol) and anhydrous potassium carbonate (254.2 mg, 1.839 mmol) in anhydrous DMF (6.0 mL) at room temperature was added phenyl 2-bromoacetate (0.755 mg, 3.678 mmol). After 20 h stirring at room temperature, additional phenyl 2-bromoacetate (1.256 g, 6.13 mmol) was added and the mixture was stirred at room temperature for 24 h. The reaction mixture was diluted with methylene chloride (70 mL), quenched with an aqueous pH 7 phosphate buffer solution (30 mL). The aqueous layer was extracted with methylene chloride (3×50 mL). The combined organic extracts were then successively washed with an aqueous pH 7 phosphate buffer solution (50 mL) and brine (50 mL), dried over MgSO4, filtered, and concentrated. The crude residue was purified by C18 reverse phase chromatography (H2O:CH3CN eluant gradient) to give phenyl 2-(5-nitro-1H-pyrrolo[2,3-b]pyridin-1-yl)acetate (C-7) as a beige solid (50.0 mg, 13% yield). MS (M+1): m/e 298.
Reaction SMILES: [F:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6](=[C:12]3[CH:16]=[C:15](OC)[CH2:14][O:13]3)[C:7](=[O:11])[NH:8]2)=[CH:4][CH:3]=1.[NH:19]1[CH2:24][CH2:23][O:22][CH2:21][CH2:20]1>CCO>[F:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6](=[C:12]3[CH:16]=[C:15]([N:19]4[CH2:24][CH2:23][O:22][CH2:21][CH2:20]4)[CH2:14][O:13]3)[C:7](=[O:11])[NH:8]2)=[CH:4][CH:3]=1
Reactant: COC1=CC(=C2C(=O)Nc3cc(F)ccc32)OC1
Reactant: C1COCCN1
Solvent: CCO
Product: O=C1Nc2cc(F)ccc2C1=C1C=C(N2CCOCC2)CO1
Temperature: 25 °C

Procedure:
A mixture of 6-fluoro-3-(4-methoxy-5H-furan-2-ylidene)-1,3-dihydro-indol-2-one (100 mg, 0.40 mmol) and morpholine (0.5 mL, 5.7 mmol) in 20 mL of EtOH was heated at reflux for 16 hours. The mixture was cooled to room temperature. The precipitates were filtered, rinsed with EtOH and dried in vacuum to give 6-fluoro-3-(4-morpholin-4-yl-5H-furan-2-ylidene)-1,3-dihydro-indol-2-one as a pale yellow powder. Yield: 55 mg, 45%.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([CH2:9][NH:10][CH3:11])=[CH:5][CH:4]=1.Cl[S:13]([C:16]1[CH:25]=[CH:24][C:19]([C:20]([O:22]C)=[O:21])=[CH:18][CH:17]=1)(=[O:15])=[O:14]>>[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([CH2:9][N:10]([CH3:11])[S:13]([C:16]2[CH:17]=[CH:18][C:19]([C:20]([OH:22])=[O:21])=[CH:24][CH:25]=2)(=[O:15])=[O:14])=[CH:5][CH:4]=1
Reactant: CNCc1ccc(OC)cc1
Reactant: COC(=O)c1ccc(S(=O)(=O)Cl)cc1
Product: COc1ccc(CN(C)S(=O)(=O)c2ccc(C(=O)O)cc2)cc1

Procedure:
Prepared as in example 5-27 from 1-(4-methoxyphenyl)-N-methylmethanamine and methyl 4-(chlorosulfonyl)-benzoate (Example 5-10c). MS (M−H, 335.1); 1H NMR (400 MHz, DMSO-d6): δ, ppm: 2.51 (s, 3H), 3.71 (s, 3H), 4.05 (s, 2H), 6.88 (d, 2H), 7.18 (d, 2H), 7.91 (d, 2H); 8.13 (d, 2H). Elemental analysis: (found): C, 57.47%, H, 4.77% and N, 4.31%; (theoretical): C, 57.30%, H, 5.11% and N, 4.18%
Reaction SMILES: Cl[C:2]1[N:10]([C:11]2[CH:12]=[N:13][CH:14]=[CH:15][CH:16]=2)[C:5]2=[N:6][CH:7]=[CH:8][CH:9]=[C:4]2[C:3]=1[CH:17]=[O:18].[C:19]([O:23][C:24]([N:26]1[CH2:31][CH2:30][NH:29][CH2:28][CH2:27]1)=[O:25])([CH3:22])([CH3:21])[CH3:20]>O1CCOCC1>[C:19]([O:23][C:24]([N:26]1[CH2:31][CH2:30][N:29]([C:2]2[N:10]([C:11]3[CH:12]=[N:13][CH:14]=[CH:15][CH:16]=3)[C:5]3=[N:6][CH:7]=[CH:8][CH:9]=[C:4]3[C:3]=2[CH:17]=[O:18])[CH2:28][CH2:27]1)=[O:25])([CH3:22])([CH3:20])[CH3:21]
Reactant: O=Cc1c(Cl)n(-c2cccnc2)c2ncccc12
Reactant: CC(C)(C)OC(=O)N1CCNCC1
Solvent: C1COCCO1
Product: CC(C)(C)OC(=O)N1CCN(c2c(C=O)c3cccnc3n2-c2cccnc2)CC1
Temperature: 95 °C
Yield: 85 %

Procedure:
A solution of 2-chloro-1-pyridin-3-yl-1H-pyrrolo[2,3-b]pyridine-3-carbaldehyde (46 mg, 0.179 mmol) in 1,4-dioxane (4 mL) is treated with piperazine-1-carboxylic acid tert-butyl ester (157 mg, 0.843 mmol) and the resulting yellow solution is heated to 95° C. under a reflux condenser for 29 hours. The reaction mixture is evaporated to give a red oil. The residue is purified by flash chromatography on a 5-gram silica gel cartridge by elution with dichloromethane:ethyl acetate (3:1, increasing to 2:1 to 1:1). Fractions containing the product are combined and the solvent evaporated to give 62 mg of 4-(3-formyl-1-pyridin-3-yl-1H-pyrrolo[2,3-b]pyridin-2-yl)-piperazine-1-carboxylic acid tert-butyl ester as a orange waxy solid (85% yield). MS: m/e 408 (M+H), 430 (M+Na). 1H NMR (300 MHz, CDCl3): 10.29 (1H, s), 8.78 (1H, d), 8.74 (1H, dd), 8.50 (1H, d), 8.20 (1H, dd), 7.94 (1H, dm), 7.59 (1H, dd), 7.22 (1H, dd), 3.39-3.28 (8H, m), 1.46 (9H, s).
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[C:6](F)[CH:5]=[CH:4][C:3]=1[S:9]([C@H:12]1[CH2:16][N:15]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[C@H:14]([C:24]([O:26][CH3:27])=[O:25])[CH2:13]1)(=[O:11])=[O:10].[F:28][C:29]([F:33])([F:32])[CH2:30][OH:31].C(=O)([O-])[O-].[Cs+].[Cs+]>CN(C)C(=O)C>[Cl:1][C:2]1[CH:7]=[C:6]([O:31][CH2:30][C:29]([F:33])([F:32])[F:28])[CH:5]=[CH:4][C:3]=1[S:9]([C@H:12]1[CH2:16][N:15]([C:17]([O:19][C:20]([CH3:21])([CH3:22])[CH3:23])=[O:18])[C@H:14]([C:24]([O:26][CH3:27])=[O:25])[CH2:13]1)(=[O:11])=[O:10]
Reactant: COC(=O)[C@@H]1C[C@@H](S(=O)(=O)c2ccc(F)cc2Cl)CN1C(=O)OC(C)(C)C
Reactant: OCC(F)(F)F
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: CC(=O)N(C)C
Product: COC(=O)[C@@H]1C[C@@H](S(=O)(=O)c2ccc(OCC(F)(F)F)cc2Cl)CN1C(=O)OC(C)(C)C
Temperature: 25 °C
Yield: 53.2 %

Procedure:
Under an atmosphere of argon, (2S,4R)-1-tert-butyl 2-methyl 4-(2-chloro-4-fluorophenylsulfonyl)pyrrolidine-1,2-dicarboxylate ([prepared in analogy to General Procedure C, steps C1-C3, using 2-chloro-4-fluorothiophenol in step C2] 1.5 g, 1.0 eq.) was combined with N,N-dimethylacetamide (15 ml) to give a light yellow solution. 2,2,2-Trifluoroethanol (854 mg, 617 μl, 8.53 mmol, Eq: 2.4) and cesium carbonate (2.09 g, 6.4 mmol, Eq: 1.8) were added. The reaction mixture was stirred over night at RT. The crude reaction mixture was concentrated in vacuo. The crude material was purified by flash chromatography (silica gel, 50 g, 0% to 50% ethyl acetate in heptane) to yield the title compound as a white foam (0.95 g, 53.2%, MS (m/e)=502.09 [M+H+]).
Reaction SMILES: Cl[C:2]1[CH:7]=[CH:6][C:5]([N+:8]([O-:10])=[O:9])=[C:4]([CH2:11][CH2:12][CH3:13])[CH:3]=1.CC1(C)C(C)(C)OB([C:22]2[CH2:23][CH2:24][N:25]([C:28]([O:30][C:31]([CH3:34])([CH3:33])[CH3:32])=[O:29])[CH2:26][CH:27]=2)O1.C([O-])([O-])=O.[Na+].[Na+]>O1CCOCC1.O.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[N+:8]([C:5]1[CH:6]=[CH:7][C:2]([C:22]2[CH2:27][CH2:26][N:25]([C:28]([O:30][C:31]([CH3:34])([CH3:33])[CH3:32])=[O:29])[CH2:24][CH:23]=2)=[CH:3][C:4]=1[CH2:11][CH2:12][CH3:13])([O-:10])=[O:9]
Reactant: CC(C)(C)OC(=O)N1CC=C(B2OC(C)(C)C(C)(C)O2)CC1
Reactant: CCCc1cc(Cl)ccc1[N+](=O)[O-]
Agent: Cl[Pd](Cl)([P](c1ccccc1)(c1ccccc1)c1ccccc1)[P](c1ccccc1)(c1ccccc1)c1ccccc1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: O
Solvent: C1COCCO1
Product: CCCc1cc(C2=CCN(C(=O)OC(C)(C)C)CC2)ccc1[N+](=O)[O-]
Temperature: 80 °C
Yield: 86.7 %

Procedure:
4-Chloro-1-nitro-2-propylbenzene (J. Organometallic Chem. 2001, 624(1-2), 167-171) (0.299 g, 1.50 mmol), 1,1-dimethylethyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3,6-dihydro-1(2H)-pyridinecarboxylate (0.553 g, 1.79 mmol), Na2CO3 (0.509 g, 4.80 mmol) and bis(triphenylphosphine)palladium(II) chloride (0.0620 g, 0.0900 mmol) in dioxane (6 mL) and H2O (3 mL) was degassed for 10 min. The mixture was heated at 80° C. overnight. The reaction was filtered through Celite®, washed with EtOAc and H2O, dried (MgSO4), concentrated and purified by flash chromatography to provide the title compound of step A (0.451 g, 1.30 mmol, 87%). 1H NMR (400 MHz, CDCl3) δ ppm 0.97 (t, J=7.3 Hz, 3H), 1.46 (s, 9H), 1.65 (sextet, J=7.5 Hz, 2H), 2.50 (br. s., 2H), 2.83-2.88 (m, 2H), 3.62 (t, J=5.7 Hz, 2H), 4.08 (q, J=2.7 Hz, 2H), 6.14 (br. s., 1H), 7.25-7.29 (m, 2H), 7.87 (d, J=7.9 Hz, 1H).
Reaction SMILES: [CH:1]1[C:14]2[CH:13]([C:15]([O:17][CH3:18])=[O:16])[C:12]3[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=3)[O:6][C:5]=2[CH:4]=[CH:3][CH:2]=1.CC(C)([O-:22])C.[K+].O=O.Cl>O1CCCC1>[OH:22][C:13]1([C:15]([O:17][CH3:18])=[O:16])[C:14]2[CH:1]=[CH:2][CH:3]=[CH:4][C:5]=2[O:6][C:7]2[C:12]1=[CH:11][CH:10]=[CH:9][CH:8]=2
Reactant: COC(=O)C1c2ccccc2Oc2ccccc21
Reactant: CC(C)(C)[O-]
Agent: Cl
Agent: O=O
Agent: [K+]
Solvent: C1CCOC1
Product: COC(=O)C1(O)c2ccccc2Oc2ccccc21

Procedure:
48.05 g (0.2 mol) methyl xanthene-9-carboxylate are dissolved in 1200 mL of tetrahydrofuran and at 0° C. combined with 23.63 g (0.2 mol) of potassium tert-butoxide. Oxygen is the piped in for 2 hours at −10° C. to −5° C., then the mixture is acidified with 2 N aqueous hydrochloric acid and the majority of the solvent is distilled off. The residue remaining is extracted with ethyl acetate and water, the organic phase is extracted with aqueous Na2S2O5 solution, washed with water, and dried, and the solvent is distilled off. The product is purified by crystallization from diisopropylether and cyclohexane. Yield: 11.10 g white crystals (22% of theoretical yield)
Reaction SMILES: [CH3:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([CH3:8])[C:3]=1[C:9]1[N:19]=[C:12]2[CH:13]=[CH:14][C:15]([CH2:17]O)=[CH:16][N:11]2[N:10]=1.O=S(Cl)[Cl:22]>>[Cl:22][CH2:17][C:15]1[CH:14]=[CH:13][C:12]2[N:11]([N:10]=[C:9]([C:3]3[C:2]([CH3:1])=[CH:7][CH:6]=[CH:5][C:4]=3[CH3:8])[N:19]=2)[CH:16]=1
Reactant: O=S(Cl)Cl
Reactant: Cc1cccc(C)c1-c1nc2ccc(CO)cn2n1
Product: Cc1cccc(C)c1-c1nc2ccc(CCl)cn2n1
Yield: 100 %

Procedure:
A solution of [2-(2,6-dimethylphenyl)-[1,2,4]triazolo[1,5-a]pyridin-6-yl]methanol (0.17 g, 0.67 mmol) in SOCl2(2.0 mL) is stirred for 2 hours at room temperature. The reaction mixture is evaporated to dryness and co-distilled with toluene to give the title compound as a yellow solid (0.198 g, 100% crude) which is used without further purification. LCMS m/z 272 (M+H)+.