Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [C:1]([O:5][C:6](=[O:25])[NH:7][CH2:8][C:9]1[C:14]([C:15]2[CH:20]=[CH:19][C:18]([Cl:21])=[CH:17][C:16]=2[Cl:22])=[CH:13][N:12]=[C:11]([NH:23][NH2:24])[CH:10]=1)([CH3:4])([CH3:3])[CH3:2].Br[C:27]#[N:28].CCOC(C)=O>CCO>[C:1]([O:5][C:6](=[O:25])[NH:7][CH2:8][C:9]1[C:14]([C:15]2[CH:20]=[CH:19][C:18]([Cl:21])=[CH:17][C:16]=2[Cl:22])=[CH:13][N:12]2[C:27]([NH2:28])=[N:24][N:23]=[C:11]2[CH:10]=1)([CH3:4])([CH3:2])[CH3:3]
Reactant: CC(C)(C)OC(=O)NCc1cc(NN)ncc1-c1ccc(Cl)cc1Cl
Reactant: N#CBr
Solvent: CCOC(C)=O
Solvent: CCO
Product: CC(C)(C)OC(=O)NCc1cc2nnc(N)n2cc1-c1ccc(Cl)cc1Cl
Temperature: 65 °C
Yield: 51.3 %

Procedure:
A mixture of the crude [5-(2,4-dichloro-phenyl)-2-hydrazino-pyridin-4-ylmethyl]-carbamic acid tert-butyl ester (1.66 g) and BrCN (638 mg, 6.0 mmol) in EtOH (40 mL) was heated at 65° C. and stirred for 2 h30. The reaction mixture was cooled to RT, poured into AcOEt (100 mL) and washed with a 2.0 M aqueous Na2CO3 solution (2×50 mL). The organic layer was dried over Na2SO4, filtered, and evaporated. The residue was purified by Combi-Flash Companion™ (Isco Inc.) column chromatography (SiO2; gradient elution, DCM/MeOH 95:5→4:6) to yield the title compound (908 mg, 2.22 mmol, 74% over 2 steps) as a brownish solid. MS: 408 [M+1]+; HPLC: AtRet=1.62; TLC: RF 0.16 (DCM/MeOH 95:5).
Reaction SMILES: Br[C:2]1[CH:3]=[CH:4][C:5]2[NH:10][CH:9]([CH3:11])[O:8][C:7]([CH3:13])([CH3:12])[C:6]=2[CH:14]=1.[Cl:15][C:16]1[CH:17]=[C:18](B(O)O)[CH:19]=[CH:20][C:21]=1[F:22].C(=O)([O-])[O-].[Na+].[Na+].C(OCC)(=O)C>COCCOC.O.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>[Cl:15][C:16]1[CH:17]=[C:18]([C:2]2[CH:3]=[CH:4][C:5]3[NH:10][CH:9]([CH3:11])[O:8][C:7]([CH3:13])([CH3:12])[C:6]=3[CH:14]=2)[CH:19]=[CH:20][C:21]=1[F:22]
Reactant: OB(O)c1ccc(F)c(Cl)c1
Reactant: CC1Nc2ccc(Br)cc2C(C)(C)O1
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
Solvent: O
Solvent: CCOC(C)=O
Product: CC1Nc2ccc(-c3ccc(F)c(Cl)c3)cc2C(C)(C)O1
Temperature: 85 °C
Reaction time: 0.25 h
Yield: 52.3 %

Procedure:
A mixture of 6-bromo-2,4,4-trimethyl-1,4-dihydro-2H-3,1-benzoxazine (3.0 g, 11.7 mmol), 3-chloro-4-fluorobenzeneboronic acid (3.1 g, 17.6 mmol), tetrakis(triphenylphosphine)palladium (0) (0.67 g, 0.59 mmol), and sodium carbonate (3.72 g, 35.1 mmol) in DME (80 mL) and water (40 mL) was subject to a blanket of nitrogen flow for 15 minutes at 50° C. and then was heated at 85° C. under nitrogen for 1 hour. The reaction was cooled to room temperature and ethyl acetate (200 mL) was added. The organic layer was washed twice with aqueous ammonium chloride (50 mL) and once with brine (50 mL), dried over sodium sulfate and concentrated to a yellow solid. The solid was triturated with ether (25 mL) and hexane (25 mL), collected on a filter, and dried to give 6-(3-chloro-4-fluorophenyl)-2,4,4-trimethyl-1,4-dihydro-2H-3,1-benzoxazine (1.87 g, 35%) as a yellow solid: mp 173-175° C.; 1H-NMR (DMSO-d6) δ 7.79 (dd, 1H, J=6.84, 2.14 Hz), 7.60-7.57 (m, 1H), 7.43-7.39 (m, 2H), 7.29 (dd, 1H, J=8.12, 2.14 Hz), 6.62 (d, 1H, J=8.54 Hz), 6.40 (s, 1H), 4.79 (q, 1H, J=5.55 Hz), 1.53 (s, 3H), 1.48 (s, 3H), 1.28 (d, 3H, J=5.55 Hz); MS (ES) m/z 306/308([M +H]+).
Reaction SMILES: [Cl:1][C:2]1[N:7]=[C:6]([NH:8][C:9]2[CH:14]=[CH:13][CH:12]=[C:11]([I:15])[CH:10]=2)[CH:5]=[CH:4][N:3]=1.[C:16](=O)([O-])[O-].[K+].[K+].CI.O>CN(C)C=O>[Cl:1][C:2]1[N:7]=[C:6]([N:8]([C:9]2[CH:14]=[CH:13][CH:12]=[C:11]([I:15])[CH:10]=2)[CH3:16])[CH:5]=[CH:4][N:3]=1
Reactant: Clc1nccc(Nc2cccc(I)c2)n1
Reactant: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: CI
Solvent: O
Product: CN(c1cccc(I)c1)c1ccnc(Cl)n1
Temperature: 20 °C
Reaction time: 5 h
Yield: 76.3 %

Procedure:
A solution of 2-chloro-N-(3-iodophenyl)pyrimidin-4-amine (1.1 g, 3.3 mmol) and potassium carbonate (0.92 g, 6.6 mmol) in N,N-dimethylformamide (6.6 mL) was treated with methyl iodide (0.52 mL, 8.3 mmol) and stirred at 20° C. for 5 h. The reaction mixture was poured into water (50 mL) and extracted with ethyl acetate (200 mL). The organic layer was separated and washed with brine (50 mL), dried over anhydrous sodium sulfate, filtered, and concentrated to a crude solid. This material was purified by flash column chromatography to give the desired product (0.87 g, 75%) as a tan oil. LCMS for C11H10ClIN3 (M+H)+: m/z=346.0.
Reaction SMILES: [Br:1][CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][C:8]1[CH:13]=[CH:12][C:11]([OH:14])=[C:10](O)[CH:9]=1.[CH2:16](Br)[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1.[C:24](=[O:27])([O-])[O-].[K+].[K+].CN(C)C=O>CC(C)=O>[Br:1][CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][C:8]1[CH:13]=[CH:12][C:11]([O:14][CH2:16][C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)=[C:10]([O:27][CH2:24][C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=2)[CH:9]=1
Reactant: Oc1ccc(CCCCCCBr)cc1O
Reactant: BrCc1ccccc1
Reactant: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: CC(C)=O
Product: BrCCCCCCc1ccc(OCc2ccccc2)c(OCc2ccccc2)c1
Reaction time: 48 h
Yield: 94.1 %

Procedure:
A mixture of 8.3 g (0.030 mol) of 1-(6-bromohexyl)-3,4-dihydroxybenzene, 18 mL (0.15 mol) of benzyl bromide and 13 g (0.09 mol) of potassium carbonate in 160 mL of acetone-50 mL of dimethylformamide was stirred at reflux for 24 hours. Potassium carbonate (4 g) was added and stirring at reflux was continued for 48 hours. The reaction mixture was cooled, filtered and the filtrate was concentrated at reduced pressure to an oil. Purification by HPLC using 1% ethyl acetate-hexane gave 6.4 g (47% yield) of 1-(6-bromohexyl)-3,4-bis-(phenylmethoxy)benzene. The nmr spectrum was consistent with the structure and the low resolution mass spectrum showed the molecular ion at m/z 452 (C26H29BrO2).
Reaction SMILES: [NH2:1][C:2]1[CH:9]=[CH:8][CH:7]=[CH:6][C:3]=1[CH2:4][OH:5].[C:10]([C:15](=[CH:21]OCC)[C:16]([O:18][CH2:19][CH3:20])=[O:17])(=[O:14])[CH:11]([CH3:13])[CH3:12]>>[C:10]([C:15](=[CH:21][NH:1][C:2]1[CH:9]=[CH:8][CH:7]=[CH:6][C:3]=1[CH2:4][OH:5])[C:16]([O:18][CH2:19][CH3:20])=[O:17])(=[O:14])[CH:11]([CH3:13])[CH3:12]
Reactant: Nc1ccccc1CO
Reactant: CCOC=C(C(=O)OCC)C(=O)C(C)C
Product: CCOC(=O)C(=CNc1ccccc1CO)C(=O)C(C)C
Temperature: 25 °C
Reaction time: 2 h
Yield: 76.5 %

Procedure:
2-aminobenzyl alcohol (12.32 g, 0.1 mol) was dissolved in ethyl 2-isobutyryl-3-ethoxyacrylate (23.57 g, 0.11 mol) stirred for 2 hours at room temperature then warmed briefly to boiling. Cooling and trituration with petroleum ether gave ethyl 2-isobutyryl-3-(2-(hydroxymethyl)phenylamino)acrylate (22.29 g, 77%) as a mixture of E/Z isomers, m.p. 72°-84°.
Reaction SMILES: [Cl-].O[NH3+:3].[C:4](=[O:7])([O-])[OH:5].[Na+].CS(C)=O.[CH3:13][O:14][C:15]1[CH:16]=[C:17]([C:23](=[O:53])[CH2:24][N:25]2[C:30](=[O:31])[C:29]3[CH:32]=[C:33]([CH2:35][CH3:36])[S:34][C:28]=3[N:27]([CH2:37][C:38]3[CH:43]=[CH:42][C:41]([C:44]4[C:45]([C:50]#[N:51])=[CH:46][CH:47]=[CH:48][CH:49]=4)=[CH:40][CH:39]=3)[C:26]2=[O:52])[CH:18]=[CH:19][C:20]=1[O:21][CH3:22]>C(Cl)(Cl)Cl>[CH3:13][O:14][C:15]1[CH:16]=[C:17]([C:23](=[O:53])[CH2:24][N:25]2[C:30](=[O:31])[C:29]3[CH:32]=[C:33]([CH2:35][CH3:36])[S:34][C:28]=3[N:27]([CH2:37][C:38]3[CH:43]=[CH:42][C:41]([C:44]4[CH:49]=[CH:48][CH:47]=[CH:46][C:45]=4[C:50]4[NH:3][C:4](=[O:7])[O:5][N:51]=4)=[CH:40][CH:39]=3)[C:26]2=[O:52])[CH:18]=[CH:19][C:20]=1[O:21][CH3:22]
Reactant: CCc1cc2c(=O)n(CC(=O)c3ccc(OC)c(OC)c3)c(=O)n(Cc3ccc(-c4ccccc4C#N)cc3)c2s1
Reactant: O=C([O-])O
Reactant: [NH3+]O
Agent: [Cl-]
Agent: [Na+]
Solvent: ClC(Cl)Cl
Solvent: CS(C)=O
Product: CCc1cc2c(=O)n(CC(=O)c3ccc(OC)c(OC)c3)c(=O)n(Cc3ccc(-c4ccccc4-c4noc(=O)[nH]4)cc3)c2s1
Temperature: 40 °C
Reaction time: 0.5 h

Procedure:
A mixture of hydroxylammonium chloride (1.23 g), sodium hydrogencarbonate (1.86 g) and dimethyl sulfoxide (15 ml) was stirred at 40° C. for 30 min, 4′-{[3-[2-(3,4-dimethoxyphenyl)-2-oxoethyl]-6-ethyl-2,4-dioxo-3,4-dihydrothieno[2,3-d]pyrimidin-1(2H)-yl]methyl}biphenyl-2-carbonitrile (1.25 g) was added, and the mixture was stirred at 90° C. for 16 hr. The reaction mixture was diluted with chloroform, washed successively with water and saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography and dissolved in methylene chloride (20 mL), N,N′-carbonyldiimidazole (0.36 g) and then 1,8-diazabicyclo[5.4.0]undec-7-ene (0.3 mL) were added, and the mixture was stirred at room temperature for 2 hr. The reaction mixture was diluted with chloroform, washed successively with saturated aqueous potassium hydrogensulfate solution and saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure. The obtained residue was purified by preparative HPLC, and the title compound was obtained as colorless crystals from a fraction with a shorter retention time (0.42 g, 31%).
Reaction SMILES: C1C(=O)N([Br:8])C(=O)C1.CC(N=NC(C#N)(C)C)(C#N)C.[F:21][C:22]1[CH:31]=[CH:30][C:25]([C:26]([O:28][CH3:29])=[O:27])=[CH:24][C:23]=1[CH3:32]>CCOC(C)=O>[Br:8][CH2:32][C:23]1[CH:24]=[C:25]([CH:30]=[CH:31][C:22]=1[F:21])[C:26]([O:28][CH3:29])=[O:27]
Reactant: COC(=O)c1ccc(F)c(C)c1
Reactant: O=C1CCC(=O)N1Br
Agent: CC(C)(C#N)N=NC(C)(C)C#N
Solvent: CCOC(C)=O
Product: COC(=O)c1ccc(F)c(CBr)c1
Temperature: 80 °C
Reaction time: 20 h

Procedure:
NBS (14.60 g) and AIBN (2.89 g) were added to a solution of the product from step (i) (9.85 g) in EtOAc (200 mL). The resulting mixture was stirred at 80° C. for 20 h. After cooling the mixture was washed with sat. sodium thiosulphate, brine, dried, filtered and the solvent removed. The crude product was purified using chromatography, to give the subtitle compound, 5.30 g.
Reaction SMILES: [CH3:1][C:2](/[CH:4]=[N:5]/[OH:6])=O.Cl.[F:8][C:9]1[CH:14]=[CH:13][C:12]([NH:15][NH2:16])=[CH:11][CH:10]=1>C(OCC)C.O.O.O.O.O.O.S([O-])([O-])(=O)=O.[Cu+2]>[F:8][C:9]1[CH:14]=[CH:13][C:12]([N:15]2[N:16]=[C:2]([CH3:1])[CH:4]=[N+:5]2[O-:6])=[CH:11][CH:10]=1
Reactant: NNc1ccc(F)cc1
Reactant: CC(=O)/C=N/O
Agent: [Cu+2]
Agent: Cl
Agent: O=S(=O)([O-])[O-]
Solvent: CCOCC
Solvent: O
Product: Cc1c[n+]([O-])n(-c2ccc(F)cc2)n1
Temperature: 23 °C
Reaction time: 16 h
Yield: 94.9 %

Procedure:
To a stirred solution of anti-pyruvic aldehyde 1-oxime (3.4 g, 39 mmol) in diethyl ether (75 mL) was added 4-fluorophenylhydrazine hydrochloride (5.85 g, 36 mmol). The reaction mixture was stirred at 23° C. for 16 h, and then concentrated under reduced pressure. The crude residue was dissolved in pyridine (120 mL). A solution of copper(II) sulfate pentahydrate (18 g, 72 mmol) in water (55 mL) was added dropwise over 4 min. The resulting mixture was stirred at reflux for 2 h. The mixture was concentrated under reduced pressure to remove excess pyridine. To the mixture was added 1.0 M aqueous hydrochloric acid. The mixture was extracted with ethyl acetate and the organic layer was separated and washed with 1.0 M aqueous hydrochloric acid until a clear amber organic layer was obtained. The organic layer was dried (MgSO4), filtered, and evaporated under reduced pressure to afford the title compound (6.6 g) as a colorless solid. The title compound was used directly in the next step without further purification.
Reaction SMILES: Br[C:2]1[CH:3]=[C:4]([C:8]2[N:12]=[C:11]([C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][N:14]=3)[O:10][N:9]=2)[CH:5]=[N:6][CH:7]=1.B1([C:25]2[CH:30]=[CH:29][CH:28]=[N:27][CH:26]=2)OCCCO1.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>[N:14]1[CH:15]=[CH:16][CH:17]=[CH:18][C:13]=1[C:11]1[O:10][N:9]=[C:8]([C:4]2[CH:5]=[N:6][CH:7]=[C:2]([C:25]3[CH:26]=[N:27][CH:28]=[CH:29][CH:30]=3)[CH:3]=2)[N:12]=1
Reactant: Brc1cncc(-c2noc(-c3ccccn3)n2)c1
Reactant: c1cncc(B2OCCCO2)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: c1ccc(-c2nc(-c3cncc(-c4cccnc4)c3)no2)nc1

Procedure:
A mixture of 3-(5-bromo-pyrid-3-yl)-5-(2-pyridyl)-1,2,4-oxadiazole 30.3 mg, 0.1 mmol), pyridine-3-boronic acid 1,3-propanediol cyclic ester (32.5 mg, 0.2 mmol), and tetrakis(triphenylphosphine)palladium(0) (Pd(PPh3)4, 15 mg, 0.013 mmol), in a solution of ethylene glycol dimethyl ether (1 mL) and 2M sodium carbonate (1 mL) was heated in a sealed vial at 100° C. for 1 hour. The reaction was cooled, diluted with dichloromethane, washed with water and saturated brine, filtered, and concentrated. Silica gel chromatography using 50% ethyl acetate in hexane and 100% ethyl acetate afforded 13 mg (43.2%) 5-(2-pyridyl)-3-[5-(3-pyridyl)-pyrid-3-yl]-1.,2,4-oxadiazole. 1H-NMR (CDCl3), δ (ppm): 9.49 (d, 1H), 9.01 (d, 1H), 8.93 (dd, 2H), 8.72 (t, 2H), 8.35 (d, 2H), 8.00 (dt, 1H), 7.59 (m, 1H), 7.47 (dd, 1H).
Reaction SMILES: [C:1]([C:6](=[CH:12][NH:13][C:14]1[CH:19]=[CH:18][C:17]([CH2:20][OH:21])=[CH:16][CH:15]=1)[C:7]([O:9][CH2:10][CH3:11])=[O:8])(=[O:5])[CH2:2][CH2:3][CH3:4].N1C=CC=CC=1.[C:28](Cl)(=[O:35])[C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1>C(Cl)(Cl)Cl>[C:1]([C:6](=[CH:12][NH:13][C:14]1[CH:15]=[CH:16][C:17]([CH2:20][O:21][C:28](=[O:35])[C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=2)=[CH:18][CH:19]=1)[C:7]([O:9][CH2:10][CH3:11])=[O:8])(=[O:5])[CH2:2][CH2:3][CH3:4]
Reactant: CCCC(=O)C(=CNc1ccc(CO)cc1)C(=O)OCC
Reactant: O=C(Cl)c1ccccc1
Solvent: ClC(Cl)Cl
Solvent: c1ccncc1
Product: CCCC(=O)C(=CNc1ccc(COC(=O)c2ccccc2)cc1)C(=O)OCC
Temperature: 25 °C
Reaction time: 8 h
Yield: 91.9 %

Procedure:
A solution of ethyl 2-butyryl-3-(4-hydroxymethylphenylamino)acrylate (49.5 g, 0.17 mol) and pyridine (50 ml) in chloroform (250 ml) was stirred at 0°-5° (ice-bath). Benzoyl chloride (22 ml, 0.19 mol) in chloroform (250 ml) was added dropwise keeping the reaction temperature below 10° C. Cooling was removed and the mixture was stirred overnight at room temperature. The mixture was washed with 2 M HCl, sodium hydrogen carbonate solution and brine, dried (anhyd. MgSO4), filtered and evaporated to an oil which crystallized on standing. The product was slurried with petroleum ether, filtered off and washed with petroleum ether to give ethyl 2-butyryl-3-(4-benzoyloxymethylphenylamino)acrylate as white crystals (61.8 g, 92%), m.p. 73° C.-5° C.
Reaction SMILES: [I:1][CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9]I.[N:11]1[C:20]2[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=2)[CH:14]=[CH:13][CH:12]=1>>[I-:1].[I-:1].[CH2:2]([N+:11]1[C:20]2[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=2)[CH:14]=[CH:13][CH:12]=1)[CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][N+:11]1[C:20]2[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=2)[CH:14]=[CH:13][CH:12]=1
Reactant: ICCCCCCCCI
Reactant: c1ccc2ncccc2c1
Product: [I-]
Product: c1ccc2c(c1)ccc[n+]2CCCCCCCC[n+]1cccc2ccccc21
Temperature: 65 °C
Yield: 89 %

Procedure:
1,8-Diiodooctane (mmol) was added to a solution (30 mL) of dry quinoline, and the solution heated for 24 hours at 65° C. The resulting precipitate was filtered, and the product washed five times with dry diethyl ether. The resulting yellow solid was isolated in an 89% yield. 1H NMR (300 MHz, DMSO-D6) δ 9.53 (1H, d, C2-H), 9.29 (1H, d, C3-H), 8.61 (1H, d, C8-H), 8.50 (1H, d, C4-H), 8.29 (1H, t, C7-H), 8.18 (1H, t, C5-H), 8.07 (1H, d, C6-H), 5.09 (2H, t, C′1-CH2), 1.96 (2H, m, C′2-CH2), 1.25 (4H, m, C′3&4-CH2); 13C NMR (75 MHz, DMSO-D6) δ 149.5, 147.4, 137.4, 135.6, 130.7, 129.9, 129.7, 122.1, 118.9, 57.3, 29.5, 28.5, 25.7.
Reaction SMILES: [N:1]([C@H:4]1[CH2:8][CH2:7][C@H:6]([O:9][Si:10]([C:13]([CH3:16])([CH3:15])[CH3:14])([CH3:12])[CH3:11])[CH2:5]1)=[N+]=[N-].[H][H].C(N(CC)CC)C.Cl[C:27]1[C:32]([C:33]([O:35][CH2:36][CH3:37])=[O:34])=[CH:31][N:30]=[C:29]([S:38][CH3:39])[N:28]=1>C(O)C.[Pt]=O>[CH2:36]([O:35][C:33]([C:32]1[C:31]([NH:1][C@H:4]2[CH2:8][CH2:7][C@H:6]([O:9][Si:10]([C:13]([CH3:16])([CH3:15])[CH3:14])([CH3:12])[CH3:11])[CH2:5]2)=[N:30][C:29]([S:38][CH3:39])=[N:28][CH:27]=1)=[O:34])[CH3:37]
Reactant: CC(C)(C)[Si](C)(C)O[C@H]1CC[C@H](N=[N+]=[N-])C1
Reactant: [H][H]
Reactant: CCOC(=O)c1cnc(SC)nc1Cl
Agent: O=[Pt]
Solvent: CCN(CC)CC
Solvent: CCO
Product: CCOC(=O)c1cnc(SC)nc1N[C@H]1CC[C@H](O[Si](C)(C)C(C)(C)C)C1

Procedure:
To a solution of (+)-(1S,3S)-(3-azido-cyclopentyloxy)-tert-butyl-dimethyl-silane (580 mg, 2.40 mmol) (from Example 29c supra) in ethanol (30 mL) was added platinum oxide (55 mg, 0.24 mmol) (Aldrich). The mixture was hydrogenated under 1 atmosphere of hydrogen overnight. The reaction mixture was then filtered, the solids were washed with tetrahydrofuran (approximately 30 mL) and the combined filtrate was concentrated to a residue that was dissolved in dioxane (50 mL). To this solution was added triethylamine (970 μL, 705 mg, 6.96 mmol) (Aldrich) and ethyl 4-chloro-2-methylthio-5-pyrimidinecarboxylate (594 mg, 2.55 mmol) (Aldrich) and the mixture was heated at reflux for 45 minutes then cooled and partitioned between ethyl acetate and water. The organic layer was collected, dried over sodium sulfate, filtered and concentrated to a residue that was purified by chromatography on a silica gel column with a 0–20% ethyl acetate in hexanes gradient to give (−)-(1S,3S)-4-[3-(tert-butyl-dimethyl-silanyloxy)-cyclopentylamino]-2-methylsulfanyl-pyrimidine-5-carboxylic acid ethyl ester as a colorless viscous oil. (Yield 910 mg, 95%).
Reaction SMILES: Cl[CH2:2][C:3]1[CH:8]=[CH:7][N:6]=[C:5]2[N:9]([S:26]([C:29]3[CH:34]=[CH:33][C:32]([CH3:35])=[CH:31][CH:30]=3)(=[O:28])=[O:27])[C:10]([C:12]3[C:16]4=[N:17][C:18]([O:23][CH3:24])=[C:19]([O:21][CH3:22])[CH:20]=[C:15]4[N:14]([CH3:25])[CH:13]=3)=[CH:11][C:4]=12.[C:36]1([OH:42])[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=1.C(=O)([O-])[O-].[K+].[K+]>C(#N)C.O.ClCCl>[CH3:24][O:23][C:18]1[N:17]=[C:16]2[C:12]([C:10]3[N:9]([S:26]([C:29]4[CH:30]=[CH:31][C:32]([CH3:35])=[CH:33][CH:34]=4)(=[O:27])=[O:28])[C:5]4=[N:6][CH:7]=[CH:8][C:3]([CH2:2][O:42][C:36]5[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=5)=[C:4]4[CH:11]=3)=[CH:13][N:14]([CH3:25])[C:15]2=[CH:20][C:19]=1[O:21][CH3:22]
Reactant: COc1cc2c(nc1OC)c(-c1cc3c(CCl)ccnc3n1S(=O)(=O)c1ccc(C)cc1)cn2C
Reactant: Oc1ccccc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: ClCCl
Solvent: O
Solvent: CC#N
Product: COc1cc2c(nc1OC)c(-c1cc3c(COc4ccccc4)ccnc3n1S(=O)(=O)c1ccc(C)cc1)cn2C
Temperature: 80 °C

Procedure:
To a solution of 0.3 g of 3-[4-chloromethyl-1-(toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyridin-2-yl]-5,6-dimethoxy-1-methyl-1H-pyrrolo[3,2-b]pyridine in 30 cm3 of acetonitrile, at a temperature in the region of 20° C., are added 0.066 cm3 of phenol and 0.486 g of potassium carbonate. The reaction medium is heated at 80° C. for 18 hours. After cooling, the reaction medium is filtered through a sinter funnel and the filtrate is concentrated under reduced pressure. The residue obtained is taken up in 5 cm3 of water and 10 cm3 of dichloromethane. After separation of the phases by settling, the organic phase is dried over magnesium sulfate, filtered and then concentrated under reduced pressure. After purification by flash column chromatography (SiO2, dichloromethane/ethyl acetate 97.5/2.5 by volume as eluents), 0.140 g of 5,6-dimethoxy-1-methyl-3-[4-phenoxymethyl-1-(toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyridin-2-yl]-1H-pyrrolo[3,2-b]pyridine is obtained with the following characteristics:
Reaction SMILES: [Cl:1][C:2]1[C:7]([N+:8]([O-:10])=[O:9])=[CH:6][CH:5]=[C:4]([Cl:11])[C:3]=1[S:12](Cl)(=[O:14])=[O:13].[NH:16]1[CH2:20][CH2:19][CH2:18][CH2:17]1.C([N:23](CC)CC)C>>[N:16]1([C:6]2[CH:5]=[C:4]([Cl:11])[C:3]([S:12]([NH2:23])(=[O:14])=[O:13])=[C:2]([Cl:1])[C:7]=2[N+:8]([O-:10])=[O:9])[CH2:20][CH2:19][CH2:18][CH2:17]1
Reactant: CCN(CC)CC
Reactant: O=[N+]([O-])c1ccc(Cl)c(S(=O)(=O)Cl)c1Cl
Reactant: C1CCNC1
Product: NS(=O)(=O)c1c(Cl)cc(N2CCCC2)c([N+](=O)[O-])c1Cl
Yield: 65.6 %

Procedure:
Following the general procedure for sulfonamide formation outlined in example 15, 2,6-dichloro-3-nitrobenzenesulfonyl chloride (151 g, 5.2 mmol), pyrrolidine (435 μL, 5.2 mmol) and triethylamine(1.1 mL, 7.8 mmol) were reacted to form the desired product (1.16 g, 68%). LC-MS m/z 325(M+).
Reaction SMILES: [C:1]([C:6]1[CH:7]=[N:8][C:9]2[C:14]([C:15]=1[NH:16][C:17]1[CH:22]=[CH:21][C:20]([OH:23])=[CH:19][C:18]=1[CH3:24])=[CH:13][CH:12]=[CH:11][C:10]=2[O:25][CH3:26])(=[O:5])[CH2:2][CH2:3][CH3:4].[C:27](OC(=O)C)(=[O:29])[CH3:28]>N1C=CC=CC=1>[C:1]([C:6]1[CH:7]=[N:8][C:9]2[C:14]([C:15]=1[NH:16][C:17]1[CH:22]=[CH:21][C:20]([O:23][C:27](=[O:29])[CH3:28])=[CH:19][C:18]=1[CH3:24])=[CH:13][CH:12]=[CH:11][C:10]=2[O:25][CH3:26])(=[O:5])[CH2:2][CH2:3][CH3:4]
Reactant: CC(=O)OC(C)=O
Reactant: CCCC(=O)c1cnc2c(OC)cccc2c1Nc1ccc(O)cc1C
Solvent: c1ccncc1
Product: CCCC(=O)c1cnc2c(OC)cccc2c1Nc1ccc(OC(C)=O)cc1C
Temperature: 25 °C
Reaction time: 18 h
Yield: 79 %

Procedure:
3-Butyryl-4-(4-hydroxy-2-methylphenylamino)-8-methoxyquinoline (1.75 g, 5 mmol) was dissolved in a mixture of acetic anhydride (10 ml) and pyridine (10 ml), stirred for 18 hours at room temperature, then the solvent evaporated, the product dissolved in dichloromethane and washed with aqueous sodium bicarbonate. Dryinq, evaporation, and recrystallisation from ethyl acetate/petroleum ether gave 3-butyryl-4-(4-acetoxy-2-methylphenylamino)-8-methoxyquinoline (1.55 g, 79%), m.p. 167°-169°.
Reaction SMILES: C(#N)C.[C:4]([O:8][C:9]([NH:11][C@@H:12]1[C:21]2[C:16](=[CH:17][C:18]([C:22]([OH:24])=O)=[CH:19][CH:20]=2)[S:15][CH2:14][CH2:13]1)=[O:10])([CH3:7])([CH3:6])[CH3:5].[NH2:25][C:26]1[CH:31]=[CH:30][N:29]=[CH:28][CH:27]=1.[I-].ClC1C=CC=C[N+]=1C>O.C(N(CC)CC)C>[C:4]([O:8][C:9]([NH:11][C@@H:12]1[C:21]2[C:16](=[CH:17][C:18]([C:22]([NH:25][C:26]3[CH:31]=[CH:30][N:29]=[CH:28][CH:27]=3)=[O:24])=[CH:19][CH:20]=2)[S:15][CH2:14][CH2:13]1)=[O:10])([CH3:5])([CH3:6])[CH3:7]
Reactant: CC(C)(C)OC(=O)N[C@H]1CCSc2cc(C(=O)O)ccc21
Reactant: Nc1ccncc1
Agent: C[n+]1ccccc1Cl
Agent: [I-]
Solvent: CCN(CC)CC
Solvent: CC#N
Solvent: O
Product: CC(C)(C)OC(=O)N[C@H]1CCSc2cc(C(=O)Nc3ccncc3)ccc21
Temperature: 25 °C
Reaction time: 8 h
Yield: 67.8 %

Procedure:
To an acetonitrile (75 ml) solution of (S)-4-(tert-butoxycarbonylamino)thiochromane-7-carboxylic acid (1.00 g) and 4-aminopyridine (335 mg) were added triethylamine (1.35 ml) and 2-chloro-1-methylpyridinium iodide (991 mg), and the mixture was stirred at room temperature overnight. Water was added to the reaction mixture and extracted with ethyl acetate. The obtained organic layer was washed with water and saturated brine and dried over anhydrous magnesium sulfate. The solvent of this solution was evaporated and purified by silica gel column chromatography (chloroform-methanol) to give the objective (S)-4-(tert-butoxycarbonylamino)-N-(4-pyridyl)thiochromane-7-carboxamide (845 mg) as pale yellow crystals.