Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: Cl[C:2]1[CH:12]=[C:11]([O:13][C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[C:5]([C:6]([O:8][CH2:9][CH3:10])=[O:7])=[CH:4][N:3]=1.[CH3:20][C:21]1[N:22]=[C:23]([NH2:26])[S:24][CH:25]=1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].O>C1(C)C=CC=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].C1(P(C2C=CC=CC=2)C2C3OC4C(=CC=CC=4P(C4C=CC=CC=4)C4C=CC=CC=4)C(C)(C)C=3C=CC=2)C=CC=CC=1>[CH3:20][C:21]1[N:22]=[C:23]([NH:26][C:2]2[CH:12]=[C:11]([O:13][C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=3)[C:5]([C:6]([O:8][CH2:9][CH3:10])=[O:7])=[CH:4][N:3]=2)[S:24][CH:25]=1
Reactant: CCOC(=O)c1cnc(Cl)cc1Oc1ccccc1
Reactant: Cc1csc(N)n1
Agent: [Pd]
Agent: CC1(C)c2cccc(P(c3ccccc3)c3ccccc3)c2Oc2c(P(c3ccccc3)c3ccccc3)cccc21
Agent: O=C(/C=C/c1ccccc1)/C=C/c1ccccc1
Solvent: Cc1ccccc1
Solvent: O
Product: CCOC(=O)c1cnc(Nc2nc(C)cs2)cc1Oc1ccccc1
Yield: 68.6 %

Procedure:
Using the method of Example 3, Step B, ethyl 6-chloro-4-phenoxynicotinate (12.0 g, 43.4 mmol), 4-methylthiazol-2-amine (4.49 g, 39.4 mmol), potassium phosphate (9.20 g, 43.4 mmol), tris(dibenzylideneacetone)-dipalladium (0) (0.902 g, 0.985 mmol) and 4,5-bis(diphenylphosphino)-9,9-dimethyl-9H-xanthene (0.627 g, 1.08 mmol) were combined in toluene (100 mL) and water (25 mL) to afford ethyl 6-(4-methylthiazol-2-ylamino)-4-phenoxynicotinate (9.6 g, 67.8% yield) as yellow solid. 1H NMR (CDCl3) δ 8.88 (s, 1H), 7.40 (m, 2H), 7.25 (m, 1H), 7.08 (m, 1H), 7.07 (m, 1H), 6.30 (d, 1H), 6.06 (s, 1H), 4.35 (q, 2H), 2.04 (s, 3H), 1.35 (t, 3H); Mass spectrum (esi) m/z=356 (100)(M+H).
Reaction SMILES: [NH2:1][C:2]1[N:7]=[C:6]([C:8]2[O:9][CH:10]=[CH:11][CH:12]=2)[C:5]([C:13]#[N:14])=[C:4](S(C)=O)[N:3]=1.Cl.[CH:19]([C:21]1[CH:28]=[CH:27][C:24]([CH2:25][NH2:26])=[CH:23][CH:22]=1)=[CH2:20].C1CCN2C(=NCCC2)CC1>COCCOC>[NH2:1][C:2]1[N:7]=[C:6]([C:8]2[O:9][CH:10]=[CH:11][CH:12]=2)[C:5]([C:13]#[N:14])=[C:4]([NH:26][CH2:25][C:24]2[CH:27]=[CH:28][C:21]([CH:19]=[CH2:20])=[CH:22][CH:23]=2)[N:3]=1
Reactant: C=Cc1ccc(CN)cc1
Reactant: CS(=O)c1nc(N)nc(-c2ccco2)c1C#N
Agent: Cl
Solvent: COCCOC
Solvent: C1CCC2=NCCCN2CC1
Product: C=Cc1ccc(CNc2nc(N)nc(-c3ccco3)c2C#N)cc1

Procedure:
From 2-amino-4-furan-2-yl-6-methanesulfinyl-pyrimidine-5-carbonitrile, 4-vinylbenzylamine hydrochloride and DBU in DME. ES-MS m/e (%): 318 (M+H+, 100).
Reaction SMILES: [CH3:1][O:2][C@@:3]1([CH3:42])[CH2:9][N:8](C(OC(C)(C)C)=O)[CH2:7][CH2:6][N:5]([C:17]2[CH:22]=[CH:21][CH:20]=[C:19]([N:23]3[C:31]4[CH:30]=[C:29]([C:32]5[CH:33]=[N:34][N:35]([CH2:37][C:38]([F:41])([F:40])[F:39])[CH:36]=5)[N:28]=[CH:27][C:26]=4[CH:25]=[N:24]3)[N:18]=2)[CH2:4]1.Cl>CO>[CH3:1][O:2][C@:3]1([CH3:42])[CH2:4][N:5]([C:17]2[N:18]=[C:19]([N:23]3[C:31]4[CH:30]=[C:29]([C:32]5[CH:33]=[N:34][N:35]([CH2:37][C:38]([F:40])([F:39])[F:41])[CH:36]=5)[N:28]=[CH:27][C:26]=4[CH:25]=[N:24]3)[CH:20]=[CH:21][CH:22]=2)[CH2:6][CH2:7][NH:8][CH2:9]1
Reactant: CO[C@@]1(C)CN(C(=O)OC(C)(C)C)CCN(c2cccc(-n3ncc4cnc(-c5cnn(CC(F)(F)F)c5)cc43)n2)C1
Agent: Cl
Solvent: CO
Product: CO[C@@]1(C)CNCCN(c2cccc(-n3ncc4cnc(-c5cnn(CC(F)(F)F)c5)cc43)n2)C1
Temperature: 25 °C
Reaction time: 4 h
Yield: 90.7 %

Procedure:
To a solution of (R)-tert-butyl 6-methoxy-6-methyl-4-(6-(6-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-c]pyridin-1-yl)pyridin-2-yl)-1,4-diazepane-1-carboxylate (100 mg, 0.17 mmol) in MeOH (5 mL) was added HCl (conc., 5 mL). The mixture was stirred at room temperature for 4 hours. It was concentrated under reduced pressure. The crude was purified by reverse phase preparative HPLC to afford 261 as a white solid (75 mg, 91%). 1H NMR (500 MHz, DMSO-d6) δ (ppm) 9.16 (s, 1H), 8.70 (s, 1H), 8.55 (s, 1H), 8.41 (s, 1H), 8.14 (s, 1H), 7.68 (t, 1H), 7.16 (d, 1H), 6.69 (d, 1H), 5.27-5.22 (m, 2H), 4.06-4.03 (m, 2H), 3.67-3.54 (m, 2H), 3.12 (s, 3H), 3.02 (s, 2H), 2.72 (s, 2H), 1.14 (s, 3H); MS (ESI) m/z: 487 [M+H]+.
Reaction SMILES: I[C:2]1[CH:3]=[CH:4][C:5]([N:8]2[CH2:14][CH2:13][CH2:12][N:11]([CH3:15])[CH2:10][CH2:9]2)=[N:6][CH:7]=1.[Cl:16][C:17]1[CH:22]=[CH:21][C:20]([C:23]2[CH:24]=[CH:25][C:26]([C:29]#[CH:30])=[N:27][CH:28]=2)=[CH:19][CH:18]=1>>[Cl:16][C:17]1[CH:18]=[CH:19][C:20]([C:23]2[CH:24]=[CH:25][C:26]([C:29]#[C:30][C:2]3[CH:3]=[CH:4][C:5]([N:8]4[CH2:14][CH2:13][CH2:12][N:11]([CH3:15])[CH2:10][CH2:9]4)=[N:6][CH:7]=3)=[N:27][CH:28]=2)=[CH:21][CH:22]=1
Reactant: C#Cc1ccc(-c2ccc(Cl)cc2)cn1
Reactant: CN1CCCN(c2ccc(I)cn2)CC1
Product: CN1CCCN(c2ccc(C#Cc3ccc(-c4ccc(Cl)cc4)cn3)cn2)CC1

Procedure:
Prepared according to general working method I from 1-(5-iodo-pyridin-2-yl)-4-methyl-[1,4]diazepan (237 mg, 0.75 mmol) and 5-(4-chloro-phenyl)-2-ethynyl-pyridine (161 mg, 0.75 mmol).
Reaction SMILES: C([Li])CCC.CCCCCC.[CH2:12]([C:15]1[CH:20]=[CH:19][C:18]([C:21]2[CH:30]=[CH:29][C:28]3[C:23](=[C:24]([F:32])[C:25]([F:31])=[CH:26][CH:27]=3)[C:22]=2[F:33])=[CH:17][CH:16]=1)[CH2:13][CH3:14].CI.[OH:36]O>O.C(O)(=O)C.O1CCCC1>[CH2:12]([C:15]1[CH:20]=[CH:19][C:18]([C:21]2[C:22]([F:33])=[C:23]3[C:28](=[CH:29][CH:30]=2)[CH:27]=[C:26]([OH:36])[C:25]([F:31])=[C:24]3[F:32])=[CH:17][CH:16]=1)[CH2:13][CH3:14]
Reactant: CCCc1ccc(-c2ccc3ccc(F)c(F)c3c2F)cc1
Reactant: OO
Agent: [Li]CCCC
Solvent: O
Solvent: CI
Solvent: CCCCCC
Product: CCCc1ccc(-c2ccc3cc(O)c(F)c(F)c3c2F)cc1
Temperature: 0 °C
Reaction time: 1 h

Procedure:
A 1.58 M butyllithium/hexane solution (16.4 ml) was added dropwise to a tetrahydrofuran (25 ml) solution of 2-(4-propylphenyl)-1,7,8-trifluoronaphthalene (6.5 g) at −65° C., and the reaction solution was stirred for 1 hour. A tetrahydrofuran (25 ml) solution of methyl iodide (3.7 g) was added dropwise to the reaction solution for 30 minutes, and then the reaction temperature was increased to 0° C. Acetic acid (1.85 ml) and 30% hydrogen peroxide (3 ml) were added to the reaction solution, followed by stirring for a while. Water was added to the reaction solution. The organic layer was removed, and the aqueous layer was extracted with ethyl acetate. The organic layers were combined, washed with water and brine, and concentrated. Then, 6-(4-propylphenyl)-3,4,5-trifluoro-2-naphthol was obtained.
Reaction SMILES: Cl[C:2]1[N:7]=[C:6]([C:8]([O:10][CH2:11][CH3:12])=[CH2:9])[CH:5]=[C:4]([CH2:13][O:14][CH2:15][C:16]([F:19])([F:18])[F:17])[N:3]=1.[CH3:20][O:21][C:22]1[CH:23]=[C:24]([CH:26]=[CH:27][C:28]=1[N:29]1[CH:33]=[C:32]([O:34][CH3:35])[N:31]=[CH:30]1)[NH2:25].C1(P(C2CCCCC2)C2C=CC=CC=2C2C=CC=CC=2)CCCCC1.C(=O)([O-])[O-].[Cs+].[Cs+]>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.O1CCOCC1>[CH2:11]([O:10][C:8]([C:6]1[CH:5]=[C:4]([CH2:13][O:14][CH2:15][C:16]([F:19])([F:18])[F:17])[N:3]=[C:2]([NH:25][C:24]2[CH:26]=[CH:27][C:28]([N:29]3[CH:33]=[C:32]([O:34][CH3:35])[N:31]=[CH:30]3)=[C:22]([O:21][CH3:20])[CH:23]=2)[N:7]=1)=[CH2:9])[CH3:12]
Reactant: COc1cn(-c2ccc(N)cc2OC)cn1
Reactant: C=C(OCC)c1cc(COCC(F)(F)F)nc(Cl)n1
Agent: [Pd+2]
Agent: CC(=O)[O-]
Agent: O=C([O-])[O-]
Solvent: C1COCCO1
Product: C=C(OCC)c1cc(COCC(F)(F)F)nc(Nc2ccc(-n3cnc(OC)c3)c(OC)c2)n1
Temperature: 120 °C

Procedure:
2-Chloro-4-(1-ethoxyvinyl)-6-((2,2,2-trifluoroethoxy)methyl)pyrimidine (0.230 g, 0.78 mmol), 3-methoxy-4-(4-methoxy-1H-imidazol-1-yl)aniline, palladium(II) acetate (0.026 g, 0.12 mmol), 2-(dicyclohexylphosphino)biphenyl (0.041 g, 0.12 mmol), cesium carbonate (0.505 g, 1.55 mmol) and dioxane (20 mL) were mixed in a vial. The vial was capped, evacuated and flushed with nitrogen. The mixture was heated by microwave irradiation at 120° C. for 1.5 h. The mixture was filtrated through pad of silica and silica was washed by EtOAc containing 10% of MeOH. The solvents were evaporated and the residue was purified by column chromatography eluting with gradient of MeOH and DCM to give the title compound as a dry film, 0.313 g (84%).
Reaction SMILES: C(O)(=O)C.C(O)=O.[C:8]([O:12][C:13]([N:15]1[CH:19]([CH2:20][O:21][C:22]2[C:26]3[CH:27]=[C:28]([Cl:31])[CH:29]=[CH:30][C:25]=3[O:24][N:23]=2)[CH2:18][O:17]C1(C)C)=[O:14])([CH3:11])([CH3:10])[CH3:9]>O>[C:8]([O:12][C:13]([NH:15][CH:19]([CH2:18][OH:17])[CH2:20][O:21][C:22]1[C:26]2[CH:27]=[C:28]([Cl:31])[CH:29]=[CH:30][C:25]=2[O:24][N:23]=1)=[O:14])([CH3:11])([CH3:10])[CH3:9]
Reactant: CC(C)(C)OC(=O)N1C(COc2noc3ccc(Cl)cc23)COC1(C)C
Solvent: CC(=O)O
Solvent: O=CO
Solvent: O
Product: CC(C)(C)OC(=O)NC(CO)COc1noc2ccc(Cl)cc12
Reaction time: 1 h
Yield: 80.9 %

Procedure:
To a mixed solution of 19 ml of acetic acid and 19 ml of formic acid is added 3.84 g of 3-[(3-tert-butoxycarbonyl-2,2-dimethyloxazolidin-4-yl)methoxy]-5-chloro-1,2-benzoisoxazole at 20°-25° C., and they are subjected to reaction at the same temperature for one hour. Subsequently, the reaction mixture is poured into 190 ml of water and they are stirred at the same temperature for one hour. The crystals precipitated are collected by filtration, to obtain 2.78 g of 3-(2-tert-butoxycarbonylamino-3-hydroxypropoxy)-5-chloro-1,2-benzoisoxazole.
Reaction SMILES: C([S@]([NH:7][C@@H:8]([C:10]1[CH:15]=[CH:14][C:13]([NH:16][S:17]([CH3:20])(=[O:19])=[O:18])=[C:12]([CH3:21])[CH:11]=1)[CH3:9])=O)(C)(C)C.[ClH:22]>O1CCOCC1>[ClH:22].[NH2:7][C@@H:8]([C:10]1[CH:15]=[CH:14][C:13]([NH:16][S:17]([CH3:20])(=[O:19])=[O:18])=[C:12]([CH3:21])[CH:11]=1)[CH3:9]
Reactant: Cc1cc([C@@H](C)N[S@](=O)C(C)(C)C)ccc1NS(C)(=O)=O
Agent: Cl
Solvent: C1COCCO1
Product: Cc1cc([C@@H](C)N)ccc1NS(C)(=O)=O
Temperature: 25 °C
Reaction time: 0.5 h

Procedure:
To N-[4-((1R)-1-{[(R)-tert-butylsulfinyl]amino}ethyl)-2-methylphenyl]methanesulfonamide (530 mg,1.60 mmol) was added 10% methanolic hydrogen chloride (5.0 ml) and dioxane (5.0 ml). The solution was stirred at ambient temperature for 30 minutes and then concentrated under reduced pressure. Diethyl ether was added to precipitate amine hydrochloride. The precipitate was then filtered, washed with diethyl ether and collected to furnish 450 mg (quant.) of the title compound as a white solid.
Reaction SMILES: Cl[C:2]1[CH:11]=[CH:10][C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[N:3]=1.[F:12][C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=1B(O)O.C([O-])([O-])=O.[K+].[K+]>COCCOC.O.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.[Pd]>[F:12][C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=1[C:2]1[CH:11]=[CH:10][C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[N:3]=1
Reactant: Clc1ccc2ccccc2n1
Reactant: OB(O)c1ccccc1F
Agent: [Pd]
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: COCCOC
Solvent: O
Product: Fc1ccccc1-c1ccc2ccccc2n1
Yield: 95.6 %

Procedure:
2-Chloroquinoline (4.9 g, 30 mmol), 2-fluorophenylboronic acid (5.0 g, 36 mmol) and K2CO3 (12 g) were dissolved in the solvent mixture of 50 mL ethylene glycol dimethyl ether and 75 mL water. To the stirred solution was added 1.7 g tetrakis(triphenylphosphine)palladium(O) and the mixture refluxed under N2 for 20 hours. The reaction mixture was cooled and the water extracted with methylene chloride three times. The combined organic phase was washed with portions of brine. The organic layer was then dried with anhydrous sodium sulfate, filtered, and evaporated of solvent. The crude material was purified on a silica gel column to give 2-(2-fluorophenyl)quinoline (6.4 g, 96% yield).
Reaction SMILES: [OH-].[NH4+].C(=O)(OCC)[O:4][C:5]1[CH:10]=[C:9]([N+:11]([O-:13])=[O:12])[CH:8]=[C:7]([F:14])[C:6]=1[F:15]>CCOC(C)=O>[F:15][C:6]1[C:7]([F:14])=[CH:8][C:9]([N+:11]([O-:13])=[O:12])=[CH:10][C:5]=1[OH:4]
Reactant: CCOC(=O)Oc1cc([N+](=O)[O-])cc(F)c1F
Agent: [NH4+]
Agent: [OH-]
Solvent: CCOC(C)=O
Product: O=[N+]([O-])c1cc(O)c(F)c(F)c1
Yield: 0.1 %

Procedure:
Step M (3): Aqueous ammonium hydroxide (5 mL) was added to a solution of 2,3-difluoro-5-nitrophenyl ethyl carbonate (250 mg, 1.0 mol) in EtOAc (4 mL). The reaction mixture was quenched with 1 N HCl. The mixture was diluted with water and extracted with EtOAc. The organic layer was washed with brine, dried over sodium sulfate, filtered, and concentrated in vacuo to afford 2,3-difluoro-5-nitrophenol (150 mg, 85% yield).
Reaction SMILES: [NH2:1][C:2]1[N:7]=[C:6]([NH2:8])[C:5]([N:9]=[O:10])=[C:4]([NH2:11])[N:3]=1.[CH:12]([O-])=[O:13].[NH4+].C(O)=O>O.[Pd]>[OH2:10].[NH2:1][C:2]1[N:7]=[C:6]([NH2:8])[C:5]([NH:9][CH:12]=[O:13])=[C:4]([NH2:11])[N:3]=1
Reactant: Nc1nc(N)c(N=O)c(N)n1
Reactant: O=C[O-]
Agent: [Pd]
Agent: [NH4+]
Solvent: O
Solvent: O=CO
Product: Nc1nc(N)c(NC=O)c(N)n1

Procedure:
A suspension of 7.9 g (0.05 mol) of 2,4,6-triamino-5-nitrosopyrimidine in 50 ml of water was mixed with 3.25 g (0.05 mol) of ammonium formate, 13.9 g (0.3 mol) of formic acid and 0.5 g of the palladium catalyst according to Example 1. This mixture was heated for 4 hours to 100° C. After cooling, the catalyst was filtered off, the filtrate concentrated to about 25 ml and neutralised with about 10 ml of 25% aqueous sodium hydroxide solution to pH 7.5. A crystal slurry thereby resulted which was filtered off with suction. In this way, there were obtained 8.1 g (87% of theory) of pale beige crystals of 2,4,6-triamino-5-formylaminopyrimidine hydrate.
Reaction SMILES: [C:1]([OH:12])(=[O:11])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9]C.[C:13](O)(=[O:25])[CH2:14]CCCCCCCCCC.C(O)(=O)CCCCCCCCCCCCC.C(O)CO>ClCCl>[C:1]([O:12][CH2:14][CH2:13][OH:25])(=[O:11])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH3:9]
Reactant: CCCCCCCCCC(=O)O
Reactant: CCCCCCCCCCCC(=O)O
Agent: CCCCCCCCCCCCCC(=O)O
Solvent: ClCCl
Solvent: OCCO
Product: CCCCCCCCC(=O)OCCO
Reaction time: 216 h

Procedure:
Decanoic acid (C10 acid), dodecanoic acid (C12 acid), and tetradecanoic acid (C14 acid)--each of 100 mmol of C10, C12 and C14 acids were dissolved in 50 ml dichloromethane, and 300 mmol of ethylene glycol were added to the solutions. Several drops of H2 SO4 were added to the mixture. The reaction mixtures were stored at room temperature for 9 days. Isolation of the esters were carried out using the same procedure as that to isolate ethylene glycol monopelargonate.
Reaction SMILES: N1C2[C:4](=[CH:5]C=CC=2)[C:3]([C:10]2[N:11]=[C:12]3[C:18]([C:19](=[O:24])[C:20]([CH3:23])([CH3:22])[CH3:21])=[CH:17][N:16](COCC[Si](C)(C)C)[C:13]3=[N:14][CH:15]=2)=C1.C(=O)([O-])[O-].[Cs+].[Cs+].[H-].[Na+].[H][H]>C(#N)C.C1(C)C=CC=CC=1.CC(C)=O>[CH3:22][C:20]([CH3:21])([CH3:23])[C:19]([C:18]1[C:12]2[C:13](=[N:14][CH:15]=[C:10]([C:3]3[CH:3]=[CH:10][N:11]=[C:5]([N:16]4[CH2:17][CH2:18][CH2:12][CH2:13]4)[CH:4]=3)[N:11]=2)[NH:16][CH:17]=1)=[O:24]
Reactant: CC(C)(C)C(=O)c1cn(COCC[Si](C)(C)C)c2ncc(-c3c[nH]c4ccccc34)nc12
Reactant: [H][H]
Agent: O=C([O-])[O-]
Agent: [Cs+]
Agent: [H-]
Solvent: CC#N
Solvent: CC(C)=O
Solvent: Cc1ccccc1
Product: CC(C)(C)C(=O)c1c[nH]c2ncc(-c3ccnc(N4CCCC4)c3)nc12
Temperature: 80 °C
Reaction time: 8 h
Yield: 35.9 %

Procedure:
Step 2—A mixture of 1-[2-(1H-indol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazin-7-yl]-2,2-dimethyl-propan-1-one (0.2 g, 0.446 mmol), 1 (0.23 g, 0.892 mmol), and cesium carbonate (0.29 g, 0.892 mmol) in 4 mL of acetonitrile was stirred at 80° C. overnight. TLC (hexanes/EtOAc 7/3) showed little conversion, so NaH 60% dispersion in oil (0.067 g, 1.672 mmol) was added and the after hydrogen evolution had stopped the reaction mixture was stirred at 130° C. under microwave irradiation for two hours before being cooled to RT. The reaction mixture was partitioned between EtOAc and saturated aqueous ammonium chloride, the aqueous layer was back extracted twice with EtOAc. Combined organic layers were dried over Na2SO4, filtered and evaporated. The residue was purified by SiO2 chromatography (hexanes/EtOAc 0-20% EtOAc) and then a second time (toluene/acetone 0-10% acetone) to give 0.028 g of 2 (10% yield)
Reaction SMILES: C1(S([N:10]2[C:18]3[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=3)[CH:12]=[C:11]2[C:19]2[CH2:20][CH2:21][N:22]([CH2:25][C:26]3[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=3)[CH2:23][CH:24]=2)(=O)=O)C=CC=CC=1>C(O)C>[CH2:25]([N:22]1[CH2:23][CH:24]=[C:19]([C:11]2[NH:10][C:18]3[C:13]([CH:12]=2)=[CH:14][CH:15]=[CH:16][CH:17]=3)[CH2:20][CH2:21]1)[C:26]1[CH:27]=[CH:28][CH:29]=[CH:30][CH:31]=1
Reactant: O=S(=O)(c1ccccc1)n1c(C2=CCN(Cc3ccccc3)CC2)cc2ccccc21
Solvent: CCO
Product: C1=C(c2cc3ccccc3[nH]2)CCN(Cc2ccccc2)C1
Temperature: 25 °C
Yield: 72.3 %

Procedure:
A solution of 1.05 gm (2.5 mMol) 1-phenylsulfonyl-2-(1-benzyl-1,2,3,6-tetrahydropyridin-4-yl)-1H-indole in 60 mL ethanol containing 15 mL 2N sodium hydroxide was heated at reflux for 18 hours. The reaction mixture was cooled to room temperature and concentrated under reduced pressure. The residue was partitioned between ethyl acetate and 2N sodium hydroxide. The phases were separated and the organic phase was washed with saturated aqueous sodium chloride, dried over sodium sulfate and concentrated under reduced pressure. The residue was subjected to silica gel chromatography, eluting with dichloromethane containing 2% methanol. Fractions shown to contain product were combined and concentrated under reduced pressure to provide 0.521 gm (74%) of the desired compound as a light tan solid.
Reaction SMILES: [H-].[Al+3].[Li+].[H-].[H-].[H-].[CH2:7]([N:9]1[C:13]([NH:14][C:15]([C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)([C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)[C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)=[C:12]([C:34]#[N:35])[CH:11]=[N:10]1)[CH3:8].[F-].[Na+].O>O1CCCC1>[NH2:35][CH2:34][C:12]1[CH:11]=[N:10][N:9]([CH2:7][CH3:8])[C:13]=1[NH:14][C:15]([C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1)([C:28]1[CH:29]=[CH:30][CH:31]=[CH:32][CH:33]=1)[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1
Reactant: CCn1ncc(C#N)c1NC(c1ccccc1)(c1ccccc1)c1ccccc1
Agent: [Al+3]
Agent: [F-]
Agent: [H-]
Solvent: O
Solvent: C1CCOC1
Product: CCn1ncc(CN)c1NC(c1ccccc1)(c1ccccc1)c1ccccc1
Yield: 44.9 %

Procedure:
To a suspension of lithium aluminum hydride (3.01 g) in tetrahydrofuran (150 ml) was added 1-ethyl-5-(tritylamino)-1H-pyrazole-4-carbonitrile (7.5 g) at room temperature. The mixture was refluxed for 55 hours. After cooling on an ice bath, sodium fluoride (13.3 g) and water (6 ml) were added to the reaction mixture. The insoluble materials were removed by filtration. The filtrate was evaporated to give 4-aminomethyl-1-ethyl-5-tritylaminopyrazole (3.4 g).
Reaction SMILES: [F:1][C:2]([F:7])([F:6])[C:3]([OH:5])=[O:4].[NH2:8][CH2:9][C:10]1[C:23]([O:24][CH3:25])=[CH:22][CH:21]=[C:20]2[C:11]=1[O:12][C:13]1[C:14]([CH2:30][C:31]([O:33]CC3C=CC=CC=3)=[O:32])=[C:15]([O:28][CH3:29])[CH:16]=[CH:17][C:18]=1[C:19]2([CH3:27])[CH3:26]>CO.[Pd]>[F:1][C:2]([F:7])([F:6])[C:3]([OH:5])=[O:4].[NH2:8][CH2:9][C:10]1[C:23]([O:24][CH3:25])=[CH:22][CH:21]=[C:20]2[C:11]=1[O:12][C:13]1[C:14]([CH2:30][C:31]([OH:33])=[O:32])=[C:15]([O:28][CH3:29])[CH:16]=[CH:17][C:18]=1[C:19]2([CH3:27])[CH3:26]
Reactant: COc1ccc2c(c1CN)Oc1c(ccc(OC)c1CC(=O)OCc1ccccc1)C2(C)C
Agent: [Pd]
Solvent: O=C(O)C(F)(F)F
Solvent: CO
Product: COc1ccc2c(c1CN)Oc1c(ccc(OC)c1CC(=O)O)C2(C)C
Yield: 95.3 %

Procedure:
A solution of 2 g (3.56 mmol) of benzyl 5-aminomethyl-3,6-dimethoxy-9,9-dimethylxanthene-4-acetate trifluoroacetate in 70 ml of methanol was stirred at room temperature under hydrogen in the presence of 200 mg of palladium/charcoal (10%). After 30 minutes the catalyst was filtered off and the filtrate was concentrated. The residue was washed with ether and dried, whereby 1.6 g of 5-aminomethyl-3,6-dimethoxy-9,9-dimethylxanthene-4-acetic acid trifluoroacetate of m.p. 178°-184° (dec.) were obtained; IR 1680, 1630, 1608, 1496 cm-1 absorbed.
Reaction SMILES: [NH2:1][C:2]1[N:7]=[C:6]([C:8]2[C:17]3[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=3)[C:11]([F:18])=[CH:10][CH:9]=2)[CH:5]=[C:4]([CH:19]([CH3:21])[CH3:20])[N:3]=1.[Br:22]Br.C(=O)(O)[O-].[Na+]>C(Cl)(Cl)(Cl)Cl.[Fe]>[NH2:1][C:2]1[N:7]=[C:6]([C:8]2[C:17]3[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=3)[C:11]([F:18])=[CH:10][CH:9]=2)[C:5]([Br:22])=[C:4]([CH:19]([CH3:21])[CH3:20])[N:3]=1
Reactant: CC(C)c1cc(-c2ccc(F)c3ccccc23)nc(N)n1
Reactant: BrBr
Agent: [Fe]
Agent: O=C([O-])O
Agent: [Na+]
Solvent: ClC(Cl)(Cl)Cl
Product: CC(C)c1nc(N)nc(-c2ccc(F)c3ccccc23)c1Br
Temperature: 25 °C
Reaction time: 1 h
Yield: 56.2 %

Procedure:
To a solution of 2-amino-4-(4-fluoronaphth-1-yl)-6-isopropylpyrimidine (free base, 0.100 g) in carbon tetrachloride (10 mL) was added iron powder (0.002 g) and bromine (0.074 g) at room temperature. The reaction mixture was stirred at room temperature for 1 hour, after which time it was poured into sodium bicarbonate solution (saturated, 30 mL). The layers were separated and the aqueous layer was extracted three times with methylene chloride (3×10 mL). The combined organic layers were evaporated to dryness. The residue was purified by preparative thin layer chromatography, eluting with hexane/ethyl acetate, and recrystallized from ether/hexane to give 2-amino-5-bromo-4-(4-fluoronaphth-1-yl)-6-isopropylpyrimidine (0.072 g), m.p. 176-180° C.
Reaction SMILES: O.[CH:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1>>[CH:2]1[C:7]2[C:6](=[CH:7][CH:2]=[CH:3][CH:4]=2)[CH:5]=[CH:4][CH:3]=1
Reactant: c1ccccc1
Solvent: O
Product: c1ccc2ccccc2c1

Procedure:
wherein m is 0 or 1; --[Ar1 ]-- represents an arylene group (for example, a phenylene group, a naphthylene group, etc.); --[Ph1 ] represents a phenyl group having a water soluble group or a hydrophilic group (as the water soluble group, for example, --SO3M, --COOM, etc., wherein M represents a cation such as an alkali metal ion, an ammonium ion, etc., or a hydrogen atom, and as the hydrophilic group, for example, an amido group, etc.); --[Ar2 ] represents a hydroxynaphthyl group having a water soluble group or a hydrophilic group (as the water soluble group, for example --SO3M, --COOM, etc., wherein M represents a cation such as an alkali metal ion, an ammonium ion, etc., or a hydrogen atom, and as the hydrophilic group, for example, an amido group, etc.), and includes, for example, the following: ##STR8## --[Het] represents an aromatic heterocyclic group, preferably an aromatic heterocyclic group having a water soluble group such as --SO3M or --COOM, wherein M represents a cation such as an alkali metal ion, an ammonium ion, etc., or a hydrogen atom, even more preferably a 5- or 6-membered nitrogen containing aromatic heterocyclic group, and includes, for example, the following: ##STR9## wherein Z represents the non-metallic atomic group necessary to form a fused aromatic ring, e.g., benzene or naphthalene; M represents a cation such as an alkali metal ion, an ammonium ion, etc., or a hydrogen atom; R'1 represents an alkyl group having 1 to 7 carbon atoms, a hydrogen atom, a phenyl group, or a naphthyl group; and R"1 represents an amino group, an alkyl group having 1 to 5 carbon atoms, an acylamino group, most preferably where the acyl moiety contains 1 to 10 carbon atoms, a sulfonamido group, a ureido group, an alkoxycarbonyl group, most preferably where the alkoxy moiety contains from 2 to 10 carbon atoms, a substituted group thereof (which applies to all of the above groups), or a carboxy group; an azomethine dye residue such as those represented by the following formulae: ##STR10## wherein m is 0 or 1; M represents a cation such as an alkali metal cation, an ammonium ion, etc., or a hydrogen atom; and R'2, R'3, R'4 and R'5 each represents an aliphatic hydrocarbon group, for example, an alkyl group having 1 to 5 carbon atoms; a xanthene type dye residue such as those represented by the following formula: ##STR11## wherein m is 0 or 1; an azine type dye residue such as those represented by the following formula: ##STR12## wherein m is 0 or 1; an indoaniline type dye residue such as those represented by the following formulae: ##STR13## wherein R'6, R'7, R'8, R'9, R'10, and R'11 each represents an aliphatic hydrocarbon group, for example, an alkyl group having 1 to 5 carbon atoms;