Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: CO[C:3](=[O:7])[CH2:4][C:5]#[N:6].[CH2:8]([NH2:12])[CH2:9][CH2:10][CH3:11].C[O:14][C:15](=O)[CH2:16][C:17]([CH3:19])=O.S(=O)(=O)(O)O>O>[CH2:8]([N:12]1[C:15]([OH:14])=[CH:16][C:17]([CH3:19])=[C:4]([C:5]#[N:6])[C:3]1=[O:7])[CH2:9][CH2:10][CH3:11]
Reactant: COC(=O)CC(C)=O
Reactant: CCCCN
Reactant: COC(=O)CC#N
Agent: O=S(=O)(O)O
Solvent: O
Product: CCCCn1c(O)cc(C)c(C#N)c1=O
Temperature: 120 °C
Yield: 85 %

Procedure:
69.3 parts of cyanoacetic acid methyl ester are added at 20° to 30° C. to 117.5 parts of n-butylamine, while stirring, the mixture is stirred for approx. 12 hours, 150 parts of water and 93.4 parts of acetoacetic acid methyl ester are added and the mixture is heated at 120° C. for 6 hours in an autoclave, a pressure of 13 bars being generated. The reaction solution is then run into a mixture of 400 parts of water and 75 parts of 61% strength sulphuric acid and the precipitate which has been formed is filtered off, rinsed with water and dried, 123 parts (85% of theory) of 1-butyl-3-cyano-4-methyl-6-hydroxypyrid-2-one with a melting point of 220° C. are obtained.
Reaction SMILES: [C:1]([N:8]1[CH:12]=[CH:11]N=C1)([N:3]1[CH:7]=[CH:6]N=[CH:4]1)=[O:2].[CH3:13][C:14](C)=[CH:15]CN.C(O)(=O)C(O)=O.[F:25][C:26]([F:39])([F:38])[C:27]1[CH:28]=[C:29]([CH:35]=[CH:36][CH:37]=1)[O:30]C1CNC1.C(N(CC)CC)C>O1CCCC1>[CH3:13][C:14]([CH3:15])=[CH:11][CH2:12][NH:8][C:1]([N:3]1[CH2:4][CH:6]([O:30][C:29]2[CH:35]=[CH:36][CH:37]=[C:27]([C:26]([F:25])([F:38])[F:39])[CH:28]=2)[CH2:7]1)=[O:2]
Reactant: O=C(n1ccnc1)n1ccnc1
Reactant: CC(C)=CCN
Reactant: FC(F)(F)c1cccc(OC2CNC2)c1
Agent: O=C(O)C(=O)O
Solvent: CCN(CC)CC
Solvent: C1CCOC1
Product: CC(C)=CCNC(=O)N1CC(Oc2cccc(C(F)(F)F)c2)C1
Temperature: 0 °C
Reaction time: 1 h
Yield: 91.4 %

Procedure:
A solution of 3.6 g (0.022 mold) of 1,1'-carbonyldiimidazole in 100 ml of tetrahydrofuran was cooled with a tap water bath and stirred under nitrogen while 1.6 g (0.022 mole) of 3-methyl-2-butenylamine was added with a syringe and needle. The reaction mixture was stirred for 1 hr, then treated with 6.2 g (0.02 mole) of 3-[3-(trifluoromethyl)phenoxy]azetidine oxalate followed in 0.5 hr with 5 ml of triethylamine and stirring continued for 72 hr. The reaction mixture was diluted with 500 ml of ice water and extracted with 6×50 ml of methylene chloride. The combined extracts were washed with water, dried over magnesium sulfate and concentrated to a solid residue on a rotary evaporator. Recrystallization from ethanol-water yielded 6 g of white crystals, m.p. 143°-144° C.
Reaction SMILES: [NH2:1][C:2]1[C:7]([F:8])=[CH:6][N:5]([S:9]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)(=[O:11])=[O:10])[C:4](=[O:18])[N:3]=1.C(=O)([O-])[O-].[K+].[K+].CN(C)C=O.I[CH2:31][CH3:32]>C(OCC)(=O)C>[C:12]1([S:9]([N:5]2[CH:6]=[C:7]([F:8])[C:2](=[NH:1])[N:3]([CH2:31][CH3:32])[C:4]2=[O:18])(=[O:10])=[O:11])[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1
Reactant: Nc1nc(=O)n(S(=O)(=O)c2ccccc2)cc1F
Reactant: CCI
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: CCOC(C)=O
Product: CCn1c(=N)c(F)cn(S(=O)(=O)c2ccccc2)c1=O
Temperature: 60 °C
Reaction time: 1 h

Procedure:
To a 25 mL sealed tube were added 4-amino-1-benzenesulfonyl-5-fluoro-1H-pyrimidine-2-one (1.0 g, 3.71 mmol), anhydrous potassium carbonate (K2CO3; 2.05 g, 14.9 mmol), and N,N-dimethylformamide (DMF; 10 mL), followed by iodoethane (EtI; 3.45 g, 22.3 mmol). The reaction vessel was sealed, and the reaction mixture was warmed to 60° C. and stirred for 1 hour. The reaction mixture was cooled to room temperature, diluted with ethyl acetate (EtOAc; 250 mL), and washed with water (H2O; 3×100 mL). The organic phase was dried over magnesium sulfate (MgSO4), filtered, and the solvent evaporated under reduced pressure. Purification by flash chromatography (SiO2, EtOAc/Hexanes gradient) afforded benzenesulfonyl-5-fluoro-4-imino-3-ethyl-3,4-dihydro-1H-pyrimidin-2-one as a pale yellow solid (200 mg; 18%): mp 163-166° C.; 1H NMR (400 MHz, DMSO-d6) δ 8.82 (m, 1H), 8.29 (d, J=6.8 Hz, 1H), 8.02 (dd, J=8.4, 1.1 Hz, 2H), 7.79 (ddd, J=6.9, 2.3, 1.1 Hz, 1H), 7.66 (dd, J=10.7, 4.9 Hz, 2H), 3.31 (q, J=7.2 Hz, 2H), 1.09 (t, J=7.2 Hz, 3H); ESIMS m/z 298 ([M+H]+).
Reaction SMILES: [NH2:1][CH2:2][CH2:3][OH:4].CO.[Cl:7][C:8]1[CH:18]=[CH:17][CH:16]=C[C:9]=1[C:10]([N+:12]([O-:14])=[O:13])=C.[ClH:19].CCO[CH2:23][CH3:24]>CC(O)C>[ClH:7].[Cl:19][C:24]1[CH:23]=[CH:16][CH:17]=[CH:18][C:8]=1[CH:9]([NH:1][CH2:2][CH2:3][OH:4])[CH2:10][N+:12]([O-:14])=[O:13]
Reactant: NCCO
Reactant: CCOCC
Reactant: C=C(c1ccccc1Cl)[N+](=O)[O-]
Agent: Cl
Solvent: CO
Solvent: CC(C)O
Product: O=[N+]([O-])CC(NCCO)c1ccccc1Cl
Reaction time: 1 h

Procedure:
A solution of 6.1 parts of 2-aminoethanol in 16 parts of methanol and 40 parts of ether is cooled on ice. Then there is added dropwise at about 5°C. a solution of 18.4 parts of o-chloro-α-nitrostyrene in 60 parts of ether. Upon completion, stirrng in an ice-bath is continued for 1 hour. The reaction mixture is acidified with an excess of 2-propanol previously saturated with gaseous hydrogen chloride. The precipitated product is filtered off, washed thoroughly with ether and dried, yielding 2-{N-[o-chloro-α-(nitromethyl)benzyl]amino} ethanol hydrochloride.
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[CH:6][C:5]([Br:8])=[CH:4][N:3]=1.C(N(CC)C(C)C)(C)C.Cl[C:19]([O:21][CH3:22])=[O:20]>C(Cl)(Cl)Cl>[CH3:22][O:21][C:19](=[O:20])[NH:1][C:2]1[CH:7]=[CH:6][C:5]([Br:8])=[CH:4][N:3]=1
Reactant: COC(=O)Cl
Reactant: Nc1ccc(Br)cn1
Solvent: ClC(Cl)Cl
Solvent: CCN(C(C)C)C(C)C
Product: COC(=O)Nc1ccc(Br)cn1
Temperature: 0 °C
Yield: 37 %

Procedure:
A solution of 2-amino-5-bromopyridine (9.46 g, 20 mmol) and N,N-diisopropylethylamine (3.10 g) in chloroform (20 ml) was added to a solution of methyl chloroformate (2.30 g, 24 mmol) in chloroform (25 ml) dropwise with stirring at 0° C. The reaction mixture was stirred for 20 minutes, filtered and the precipitate was washed with chloroform and dried to afford 1.71 g (37%) of the title product as a white solid. mp 191-192° C. 1H NMR (CDCl3): δ=8.42 (d, 1 H); 8.30 (d, 1 H); 7.91 (d, 1 H); 7.77 (d of d, 1 H); 3.79 (s, 3 H). MS (EI): m/z=230, 232 (M+, Br isotopes).
Reaction SMILES: [CH2:1]([C:4]1[C:17]([OH:18])=[C:16]([CH3:19])[C:15]2[O:14][C:13]3[C:8](=[C:9]([F:20])[CH:10]=[CH:11][CH:12]=3)[C:7](=[O:21])[C:6]=2[CH:5]=1)[CH:2]=C.ClC1C=CC=C(C(OO)=O)C=1.C(Cl)(Cl)Cl.[C:37](=[O:40])([O-])[O-:38].[K+].[K+]>O>[F:20][C:9]1[C:8]2[C:7](=[O:21])[C:6]3[CH:5]=[C:4]4[CH2:1][CH:2]([C:37]([OH:38])=[O:40])[O:18][C:17]4=[C:16]([CH3:19])[C:15]=3[O:14][C:13]=2[CH:12]=[CH:11][CH:10]=1
Reactant: O=C([O-])[O-]
Reactant: C=CCc1cc2c(=O)c3c(F)cccc3oc2c(C)c1O
Agent: O=C(OO)c1cccc(Cl)c1
Agent: [K+]
Solvent: O
Solvent: ClC(Cl)Cl
Product: Cc1c2c(cc3c(=O)c4c(F)cccc4oc13)CC(C(=O)O)O2
Temperature: 25 °C
Reaction time: 5 h
Yield: 50.3 %

Procedure:
A mixture of 2-allyl-8-fluoro-3-hydroxy-4-methyl-9-oxo-9H-xanthene (9.0 g), m-chloroperbenzoic acid (8.0 g) and chloroform (1,000 ml) was stirred at room temperature for 5 hours and left to stand overnight. To the mixture, potassium carbonate (20 g) and water (500 ml) were added and the resulting mixture was extracted with chloroform. The chloroform layer was dried and the solvent was distilled off. The residue was dissolved in acetone (1,000 ml) and to the stirred solution, a mixture of chromium trioxide (21 g), water (120 ml) and concentrated sulfuric acid (36 g) was added dropwise at room temperature. After leaving it to stand overnight, the mixture was filtered and the filtrate was evaporated to dryness under vacuum. After addition of water, the solid crystal was recovered by filtration, washed with water and dried. Recrystallization from ethanol gave 5.0 g of 6-fluoro-2,3-dihydro-11-methyl-5-oxo-5H-furo[3,2-b]xanthene-2-carboxylic acid. m.p. 292°-295° C. This compound produced a mass spectrum having a molecular ion peak at m/e 314.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[CH:4][CH:5]=[C:6]2[C:10]=1[NH:9][C:8]([CH3:11])=[CH:7]2.[OH-].[K+].Br[CH2:15][CH2:16][CH2:17][S:18][CH3:19]>COCCOCCN(CCOCCOC)CCOCCOC>[Cl:1][C:2]1[CH:3]=[CH:4][CH:5]=[C:6]2[C:10]=1[N:9]([CH2:15][CH2:16][CH2:17][S:18][CH3:19])[C:8]([CH3:11])=[CH:7]2
Reactant: Cc1cc2cccc(Cl)c2[nH]1
Reactant: CSCCCBr
Agent: COCCOCCN(CCOCCOC)CCOCCOC
Agent: [K+]
Agent: [OH-]
Product: CSCCCn1c(C)cc2cccc(Cl)c21
Reaction time: 2 h
Yield: 81.4 %

Procedure:
1.5 g of 7-chloro-2-methyl-1H-indole are mixed with stirring with 1.1 g of ground potassium hydroxide and 0.2 g of TDA-1. The mixture is left stirring for 2 hours at AT, then 3.1 g of 1-bromo-3-methylsulphanylpropane are added dropwise and the mixture is heated at reflux for 24 hours. Ground potassium hydroxide (0.5 g), TDA-1 (0.1 g) and 1.6 g of 1-bromo-3-methylsulphanylpropane are again added. After heating at reflux for 9 hours, 1.6 g of 1-bromo-3-methylsulphanylpropane are again added and the mixture is heated at reflux for 24 hours. The mixture is allowed to return to AT and is then extracted with toluene. The organic phase is washed with a 10% HCl solution, with water and then a saturated NaCl solution. It is dried and evaporated and then the residue is chromatographed on silica while eluting with a cyclohexane/toluene (50/50, v/v) mixture. 1.87 g of the expected compound are obtained.
Reaction SMILES: [CH2:1]([O:3][C:4]1[CH:9]=[CH:8][C:7](B(O)O)=[CH:6][C:5]=1[CH3:13])[CH3:2].Br[C:15]1[CH:16]=[C:17]([CH:19]=[CH:20][CH:21]=1)[NH2:18].C([O-])([O-])=O.[Na+].[Na+]>COCCOC.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>[CH2:1]([O:3][C:4]1[CH:9]=[CH:8][C:7]([C:15]2[CH:21]=[CH:20][CH:19]=[C:17]([NH2:18])[CH:16]=2)=[CH:6][C:5]=1[CH3:13])[CH3:2]
Reactant: CCOc1ccc(B(O)O)cc1C
Reactant: Nc1cccc(Br)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: COCCOC
Product: CCOc1ccc(-c2cccc(N)c2)cc1C
Temperature: 25 °C
Yield: 67 %

Procedure:
4-ethoxy-3-methylphenyl boronic acid (0.125 g, 0.693 mmol) and 3-bromoaniline (0.05 mL, 0.462 mmol) were combined in DME (2 mL) in a flame-dried, round-bottom flask. Na2CO3 (2M, 0.485 mL, 0.970 mmol) and Pd(PPh3)4 (0.017 g, 0.014 mmol) were added to the stirred solution. The reaction was refluxed overnight under argon flow, and subsequently cooled to room temperature. The solvent was removed under vacuum and the resulting residue was resuspended in H20 and extracted with CH2Cl2. The organic phase was dried over MgSO4 and concentrated under vacuum. The crude product was purified by silica column chromatography (0-20% EtOAc/hexanes). The purification was monitored by TLC. The solvent was removed under vacuum from fractions containing product, resulting in 0.071 g in 67% yield.
Reaction SMILES: [NH2:1][C:2]1[C:6]([CH3:7])=[CH:5][S:4][C:3]=1[C:8]([O:10]C)=O.O.[NH2:13][NH2:14]>C(O)CCC>[NH2:1][C:2]1[C:6]([CH3:7])=[CH:5][S:4][C:3]=1[C:8]([NH:13][NH2:14])=[O:10]
Reactant: NN
Reactant: COC(=O)c1scc(C)c1N
Solvent: CCCCO
Solvent: O
Product: Cc1csc(C(=O)NN)c1N

Procedure:
A solution of methyl 3-amino-4-methyl-2-thenoate (25 g) and hydrazine hydrate (20 ml) in butanol (150 ml) was heated under reflux for 18 hours. On cooling the solvent was removed and teh residue was recrystallised from toluene to give the title product, m.p. 141-143° C.
Reaction SMILES: Cl[C:2]1[N:7]=[C:6]([Cl:8])[C:5]([C:9]([F:12])([F:11])[F:10])=[CH:4][N:3]=1.[NH3:13]>>[NH2:13][C:2]1[N:7]=[C:6]([Cl:8])[C:5]([C:9]([F:12])([F:11])[F:10])=[CH:4][N:3]=1
Reactant: N
Reactant: FC(F)(F)c1cnc(Cl)nc1Cl
Product: Nc1ncc(C(F)(F)F)c(Cl)n1
Temperature: 5 °C
Yield: 45 %

Procedure:
With stirring, 1.0 g of 2,4-dichloro-5-(trifluoromethyl)pyrimidine, Aldrich order no. 684864, is added to a methanolic ammonia solution (ca. 8 mol of ammonia in methanol) cooled to ca. 5° C., the mixture is heated to 25° C. and stirred for 2 hours at this temperature. The mixture is concentrated by evaporation and added to water. After filtering off with suction, 0.56 g of a mixture of 4-amino-2-chloro-5-trifluoromethylpyrimidine (ca. 45%) and 2-amino-4-chloro-5-trifluoromethylpyrimidine (ca. 45%) is obtained.
Reaction SMILES: Br[C:2]1[S:3][C:4]([C:7]([C:9]2[C:17]3[C:12](=[N:13][CH:14]=[CH:15][CH:16]=3)[NH:11][CH:10]=2)=[O:8])=[CH:5][N:6]=1.[Cl:18][C:19]1[CH:26]=[CH:25][C:22]([CH2:23][NH2:24])=[CH:21][CH:20]=1.C(N(CC)C(C)C)(C)C.O>O1CCCC1>[Cl:18][C:19]1[CH:26]=[CH:25][C:22]([CH2:23][NH:24][C:2]2[S:3][C:4]([C:7]([C:9]3[C:17]4[C:12](=[N:13][CH:14]=[CH:15][CH:16]=4)[NH:11][CH:10]=3)=[O:8])=[CH:5][N:6]=2)=[CH:21][CH:20]=1
Reactant: O=C(c1cnc(Br)s1)c1c[nH]c2ncccc12
Reactant: NCc1ccc(Cl)cc1
Solvent: C1CCOC1
Solvent: CCN(C(C)C)C(C)C
Solvent: O
Product: O=C(c1cnc(NCc2ccc(Cl)cc2)s1)c1c[nH]c2ncccc12
Temperature: 25 °C
Reaction time: 8 h
Yield: 27.1 %

Procedure:
A mixture of (2-Bromo-thiazol-5-yl)-(1H-pyrrolo[2,3-b]pyridin-3-yl)-methanone (99, 5 mg, 0.02 mmol), p-chlorobenzylamine (61, 10 mg, 0.08 mmol), and N,N-Diisopropylethylamine (10 μL, 0.08 mmol) in tetrahydrofuran (10 mL), in a sealed reaction vessel, was stirred room temperature overnight. The reaction mixture was poured into iced water, extracted with ethyl acetate, washed with brine, and dried over magnesium sulfate. After removal of solvent, the residue was purified by silica gel column chromatography eluting with ethyl acetate in hexane to provide the compound as a light yellow solid (P-0077, 2 mg, 30%). MS (ESI) [M+H+]=305.90, 307.88.
Reaction SMILES: N[CH:2]1[CH2:7][CH2:6][N:5]([CH2:8][C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)[CH2:4][CH2:3]1.[CH2:15]=O.[BH3-][C:18]#[N:19].[Na+]>O>[CH3:15][N:19]([CH3:18])[CH:2]1[CH2:7][CH2:6][N:5]([CH2:8][C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)[CH2:4][CH2:3]1
Reactant: [BH3-]C#N
Reactant: NC1CCN(Cc2ccccc2)CC1
Reactant: C=O
Agent: [Na+]
Solvent: O
Product: CN(C)C1CCN(Cc2ccccc2)CC1
Temperature: 25 °C
Reaction time: 1 h
Yield: 80 %

Procedure:
To a solution of 4-amino-1-benzylpiperidine (1.47 g, 7.7 mmol) in CF3 CH2OH (14 ml) were added molecular sieve 4 Å (5), and paraformaldehyde (0.51 g, 17 mmol). After stirring at RT for 1 h, NaCNBH3 (2.5 g, 39.8 mmol) was added and stirred for 16 h at RT. The reaction was stopped by addition of H2O and the product was extracted with (4:1) (Et2O:CH2Cl2). Organic fractions were combined and washed with brine (2×), dried over MgSO4, filtered and concentrated to give a crude material which was purified by silica flash chromatography to afford 4-dimethylamino-1-benzylpiperidine (80% yield). FAB Mass [M+1]+35Cl 219.
Reaction SMILES: [C:1]([O:5][C:6]([NH:8][C:9]1([CH2:18][C:19]([O:21][CH2:22][CH3:23])=[O:20])[CH2:16][CH:15]2[NH:17][CH:11]([CH2:12][O:13][CH2:14]2)[CH2:10]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].Br[CH2:25][C:26]1[NH:31][C:30]([C:32]2[S:33][CH:34]=[CH:35][N:36]=2)=[N:29][C@@H:28]([C:37]2[CH:42]=[CH:41][C:40]([F:43])=[CH:39][C:38]=2[Cl:44])[C:27]=1[C:45]([O:47][CH3:48])=[O:46].CCN(C(C)C)C(C)C>C(Cl)Cl>[C:1]([O:5][C:6]([NH:8][C:9]1([CH2:18][C:19]([O:21][CH2:22][CH3:23])=[O:20])[CH2:10][CH:11]2[N:17]([CH2:25][C:26]3[NH:31][C:30]([C:32]4[S:33][CH:34]=[CH:35][N:36]=4)=[N:29][C@@H:28]([C:37]4[CH:42]=[CH:41][C:40]([F:43])=[CH:39][C:38]=4[Cl:44])[C:27]=3[C:45]([O:47][CH3:48])=[O:46])[CH:15]([CH2:14][O:13][CH2:12]2)[CH2:16]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]
Reactant: COC(=O)C1=C(CBr)NC(c2nccs2)=N[C@H]1c1ccc(F)cc1Cl
Reactant: CCOC(=O)CC1(NC(=O)OC(C)(C)C)CC2COCC(C1)N2
Solvent: CCN(C(C)C)C(C)C
Solvent: ClCCl
Product: CCOC(=O)CC1(NC(=O)OC(C)(C)C)CC2COCC(C1)N2CC1=C(C(=O)OC)[C@H](c2ccc(F)cc2Cl)N=C(c2nccs2)N1
Temperature: 25 °C
Reaction time: 12 h

Procedure:
A mixture of ethyl 2-[7-(tert-butoxycarbonylamino)-3-oxa-9-azabicyclo[3.3.1]nonan-7-yl]acetate 146a (0.1 g, 0.3 mmol) and methyl (4R)-6-(bromomethyl)-4-(2-chloro-4-fluoro-phenyl)-2-thiazol-2-yl-1,4-dihydropyrimidine-5-carboxylate C (90 mg, 0.2 mmol), DIPEA (77.4 mg, 0.6 mmol) in DCM (5 mL) was stirred for 12 hours at room temperature. The mixture was concentrated to give crude methyl (4R)-6-[[7-(tert-butoxycarbonylamino)-7-(2-ethoxy-2-oxo-ethyl)-3-oxa-9-azabicyclo[3.3.1]nonan-9-yl]methyl]-4-(2-chloro-4-fluoro-phenyl)-2-thiazol-2-yl-1,4-dihydropyrimidine-5-carboxylate 146b. MS: calc'd (MH+) 692, exp (MH+) 692.
Reaction SMILES: C([Li])CCC.CN(C)CCN(C)C.[CH-:14]1[CH:18]=[CH:17][CH:16]=[CH:15]1.[CH-:19]1[CH:23]=[CH:22][CH:21]=[CH:20]1.[Fe+2:24].F[B:26]([C:36]1[C:41]([CH3:42])=[CH:40][C:39]([CH3:43])=[CH:38][C:37]=1[CH3:44])[C:27]1[C:32]([CH3:33])=[CH:31][C:30]([CH3:34])=[CH:29][C:28]=1[CH3:35]>CCCCCC>[C:28]1([CH3:35])[CH:29]=[C:30]([CH3:34])[CH:31]=[C:32]([CH3:33])[C:27]=1[B:26]([C:36]1[C:37]([CH3:44])=[CH:38][C:39]([CH3:43])=[CH:40][C:41]=1[CH3:42])[C-:14]1[CH:18]=[CH:17][CH:16]=[CH:15]1.[C-:19]1([B:26]([C:36]2[C:37]([CH3:44])=[CH:38][C:39]([CH3:43])=[CH:40][C:41]=2[CH3:42])[C:27]2[C:32]([CH3:33])=[CH:31][C:30]([CH3:34])=[CH:29][C:28]=2[CH3:35])[CH:23]=[CH:22][CH:21]=[CH:20]1.[Fe+2:24]
Reactant: c1cc[cH-]c1
Reactant: Cc1cc(C)c(B(F)c2c(C)cc(C)cc2C)c(C)c1
Agent: [Fe+2]
Agent: CN(C)CCN(C)C
Agent: [Li]CCCC
Solvent: CCCCCC
Product: Cc1cc(C)c(B(c2c(C)cc(C)cc2C)[c-]2cccc2)c(C)c1
Temperature: 25 °C

Procedure:
15.4 ml (24.7 mmol) of a 1.6 M solution of n-butyllithium in n-hexane were added dropwise to a mixture of 2.87 g=3.7 ml (24.7 mmol) of N,N,N′,N′-tetramethylethylenediamine and 4 ml of n-hexane over a period of 5 minutes while stirring at room temperature. The reaction mixture was stirred for another 20 minutes at room temperature and a solution of 1.86 g (10 mmol) of ferrocene in 70 ml of n-hexane was then added dropwise over a period of 25 minutes. The reaction mixture was stirred at room temperature for 6 hours and a solution of 6.62 g (24.7 mmol) of fluorodimesitylborane in n-hexane was then added dropwise over a period of 30 minutes. After stirring at room temperature for 16 hours the n-hexane was removed on a rotary evaporator, the red, semisolid residue was taken up in 400 ml of dichloromethane, the organic phase was admixed with 3 ml of water, stirred vigorously for 30 minutes and subsequently dried over magnesium sulfate. After the desiccant had been filtered off, the organic phase was evaporated to dryness. The red crude product (about 6.8 g, purity according to HPLC: 95-98%) was stirred once with hot n-hexane and subsequently recrystallized from ethanol until a purity of 99.8% as determined by HPLC had been reached. The yield, at a purity of 99.8% as determined by HPLC, was 4.7 g, corresponding to 68.8%.
Reaction SMILES: [CH2:1]([O:8][CH2:9][CH2:10][N:11]1[C:15]2=[N:16][C:17]([C:20]#N)=[CH:18][CH:19]=[C:14]2[C:13]([CH:22]2[CH2:27][CH2:26][CH2:25][CH2:24][CH2:23]2)=[CH:12]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:28](Cl)(=[O:30])[CH3:29].C([OH:34])C>>[CH2:1]([O:8][CH2:9][CH2:10][N:11]1[C:15]2=[N:16][C:17]([C:20]([O:30][CH2:28][CH3:29])=[O:34])=[CH:18][CH:19]=[C:14]2[C:13]([CH:22]2[CH2:27][CH2:26][CH2:25][CH2:24][CH2:23]2)=[CH:12]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: CCO
Reactant: CC(=O)Cl
Reactant: N#Cc1ccc2c(C3CCCCC3)cn(CCOCc3ccccc3)c2n1
Product: CCOC(=O)c1ccc2c(C3CCCCC3)cn(CCOCc3ccccc3)c2n1
Temperature: 25 °C
Yield: 70 %

Procedure:
To a solution of 1-(2-benzyloxyethyl)-3-cyclohexyl-1H-pyrrolo[2,3-b]pyridine-6-carbonitrile (1.44 g, 4.00 mmol) in ethanol (30 ml) was added acetyl chloride (8.5 ml, 120 mmol) under ice-cooling, and the mixture was heated under reflux for 3 hr. The mixture was allowed to cool to room temperature, and the solvent was evaporated under reduced pressure. The residue was dissolved in ethyl acetate and water was added. The mixture was extracted with ethyl acetate, and the organic layer was washed successively with water and saturated brine, and dried over anhydrous magnesium sulfate. After filtration, the solvent was evaporated under reduced pressure and the residue was purified by silica gel chromatography (hexane:ethyl acetate=4:1) to give ethyl 1-(2-benzyloxyethyl)-3-cyclohexyl-1H-pyrrolo[2,3-b]pyridine-6-carboxylate (1.14 g, yield 70%).
Reaction SMILES: C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[C:20]([O:24][C:25]([N:27]1[CH2:32][CH2:31][CH:30](O)[CH2:29][CH2:28]1)=[O:26])([CH3:23])([CH3:22])[CH3:21].N(C(OCC)=O)=NC([O:38][CH2:39][CH3:40])=O.[S:46]1C=CC=C1CC(O)=O>O1CCCC1.C(OCC)(=O)C>[C:20]([O:24][C:25]([N:27]1[CH2:32][CH2:31][CH:30]([S:46][C:39](=[O:38])[CH3:40])[CH2:29][CH2:28]1)=[O:26])([CH3:23])([CH3:22])[CH3:21]
Reactant: CC(C)(C)OC(=O)N1CCC(O)CC1
Reactant: CCOC(=O)N=NC(=O)OCC
Reactant: O=C(O)Cc1cccs1
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: CCOC(C)=O
Solvent: C1CCOC1
Product: CC(=O)SC1CCN(C(=O)OC(C)(C)C)CC1
Temperature: -78 °C
Reaction time: 18 h
Yield: 16 %

Procedure:
Triphenylphosphine (7.37 g) and Intermediate 11 (4.71 g) were dissolved in tetrahydrofuran (40 ml), under a nitrogen atmosphere, and cooled to −78° C. Diethyl azodicarboxylate (4.42 ml) was added via syringe, followed by thiolacetic acid (2.17 ml). The reaction was then stirred for 18 h, slowly warming to room temperature. The reaction was reduced in vacuo and the residue redissolved in ethyl acetate (150 ml) and washed with saturated sodium bicarbonate solution (3×20 ml), water (2×20 ml) and saturated brine (20 ml). The organic phase was then dried (Na2SO4), and diluted with hexane (150-200 ml). The resultant precipitate was removed by filtration, and the filtrate evaporated under reduced pressure. The pale green residue was then purified by silica gel column chromatography with 1% methanol in dichloromethane as eluent to yield the title compound as a colourless oil (0.99 g, 16%).
Reaction SMILES: [C:1]([C:5]1[CH:24]=[CH:23][C:8]([C:9]([NH:11][C:12]2[CH:22]=[CH:21][C:15]([C:16]([O:18][CH2:19][CH3:20])=[O:17])=[CH:14][CH:13]=2)=O)=[CH:7][CH:6]=1)([CH3:4])([CH3:3])[CH3:2].P(Cl)(Cl)(Cl)(Cl)Cl.[NH2:31][C:32]1[CH:42]=[CH:41][C:35]([C:36]([O:38][CH2:39][CH3:40])=[O:37])=[CH:34][CH:33]=1>>[CH2:19]([O:18][C:16]([C:15]1[CH:21]=[CH:22][C:12]([NH:11][C:9](=[N:31][C:32]2[CH:33]=[CH:34][C:35]([C:36]([O:38][CH2:39][CH3:40])=[O:37])=[CH:41][CH:42]=2)[C:8]2[CH:23]=[CH:24][C:5]([C:1]([CH3:4])([CH3:3])[CH3:2])=[CH:6][CH:7]=2)=[CH:13][CH:14]=1)=[O:17])[CH3:20]
Reactant: CCOC(=O)c1ccc(NC(=O)c2ccc(C(C)(C)C)cc2)cc1
Reactant: CCOC(=O)c1ccc(N)cc1
Agent: ClP(Cl)(Cl)(Cl)Cl
Product: CCOC(=O)c1ccc(N=C(Nc2ccc(C(=O)OCC)cc2)c2ccc(C(C)(C)C)cc2)cc1

Procedure:
N,N'-Bis(4-ethoxycarbonylphenyl)-4-t-butylbenzamidine (14) was prepared from ethyl 4-[N-(4-t-butylbenzoyl)]aminobenzoate, phosphorus pentachloride, and ethyl 4-aminobenzoate; yellow solid: mp 212°-219° C. 1H-NMR (CDCl3) 8.0-7.0 (m, 12H), 6.0 (br s, 1H), 4.3 (q, 4H, J=7 Hz), 1.4 (t, 6H, J=7 Hz), 1.3 (s, 9H); IR (Nujol) 3330, 1710, 1590; MS (m/e) 472 (M+), 308 (base).
Reaction SMILES: C(O[C:6]([N:8]1[CH2:12][C:11](=[N:13][O:14][CH2:15][C:16]2[CH:21]=[CH:20][C:19]([Cl:22])=[C:18]([Cl:23])[CH:17]=2)[CH2:10][C@H:9]1[C:24]([OH:26])=O)=[O:7])(C)(C)C.[C:27]1([CH:33]([C:37]2[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=2)C(Cl)=O)[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1.[CH2:43]([NH2:46])[CH:44]=[CH2:45]>>[CH2:43]([NH:46][C:24]([C@@H:9]1[CH2:10][C:11](=[N:13][O:14][CH2:15][C:16]2[CH:21]=[CH:20][C:19]([Cl:22])=[C:18]([Cl:23])[CH:17]=2)[CH2:12][N:8]1[C:6](=[O:7])[CH:33]([C:27]1[CH:28]=[CH:29][CH:30]=[CH:31][CH:32]=1)[C:37]1[CH:38]=[CH:39][CH:40]=[CH:41][CH:42]=1)=[O:26])[CH:44]=[CH2:45]
Reactant: C=CCN
Reactant: CC(C)(C)OC(=O)N1CC(=NOCc2ccc(Cl)c(Cl)c2)C[C@H]1C(=O)O
Reactant: O=C(Cl)C(c1ccccc1)c1ccccc1
Product: C=CCNC(=O)[C@@H]1CC(=NOCc2ccc(Cl)c(Cl)c2)CN1C(=O)C(c1ccccc1)c1ccccc1

Procedure:
Following the general method as outlined in Example 22, starting from (2S,4EZ)-1-(tert-butoxycarbonyl)-4-{[(3,4-dichlorobenzyl)oxy]imino}-2-pyrrolidinecarboxylic acid, diphenylacetyl chloride, and allylamine the title compound was obtained in 54% purity by LC/MS. MS(ESI+): m/z=536.6.