Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: B([O-])([O-])O[C:3]1[CH:8]=[CH:7][C:6]([O:9][CH2:10][CH2:11][CH2:12][O:13][CH2:14][CH2:15][CH3:16])=[CH:5][CH:4]=1.Br[C:20]1[CH:21]=[CH:22][C:23]2[N:29]([CH:30]=[O:31])[CH2:28][CH2:27][C:26]([C:32]([NH:34][C:35]3[CH:40]=[CH:39][C:38]([CH2:41][N:42]([CH3:49])[CH:43]4[CH2:48][CH2:47][O:46][CH2:45][CH2:44]4)=[CH:37][CH:36]=3)=[O:33])=[CH:25][C:24]=2[CH:50]=1.C(=O)([O-])[O-].[K+].[K+]>C1(C)C=CC=CC=1.C(O)C.O.C(OCC)(=O)C.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>[CH:30]([N:29]1[C:23]2[CH:22]=[CH:21][C:20]([C:3]3[CH:8]=[CH:7][C:6]([O:9][CH2:10][CH2:11][CH2:12][O:13][CH2:14][CH2:15][CH3:16])=[CH:5][CH:4]=3)=[CH:50][C:24]=2[CH:25]=[C:26]([C:32]([NH:34][C:35]2[CH:36]=[CH:37][C:38]([CH2:41][N:42]([CH3:49])[CH:43]3[CH2:48][CH2:47][O:46][CH2:45][CH2:44]3)=[CH:39][CH:40]=2)=[O:33])[CH2:27][CH2:28]1)=[O:31]
Reactant: CN(Cc1ccc(NC(=O)C2=Cc3cc(Br)ccc3N(C=O)CC2)cc1)C1CCOCC1
Reactant: CCCOCCCOc1ccc(OB([O-])[O-])cc1
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: [K+]
Solvent: CCOC(C)=O
Solvent: CCO
Solvent: O
Product: CCCOCCCOc1ccc(-c2ccc3c(c2)C=C(C(=O)Nc2ccc(CN(C)C4CCOCC4)cc2)CCN3C=O)cc1
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 65.7 %

Procedure:
In a mixture of water ethanol toluene (1:1:10, v/v, 18.0 ml) were dissolved 4-(3-propoxy)propoxyphenyl borate (270 mg) and 7-bromo-1-formyl-N-[4-[[N-methyl-N-(tetrahydro-2H-pyran-4-yl)amino]methyl]phenyl]-2,3-dihydro-1H-1-benzazepine-4-carboxamide (377 mg). To the solution was added potassium carbonate (251 mg), and the mixture was stirred under argon atmosphere at room temperature for 30 minutes. To the mixture was added tetrakistriphenylphosphinepalladium (35 mg), and the mixture was heated to reflux under argon atmosphere for 10 hours. The mixture was diluted with ethyl acetate, and washed with water and saturated brine, and the organic layer was dried with anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure, and the residue was purified with silica gel column chromatography (25 g, ethyl acetate→ethyl acetate:ethanol=10:1→ethyl acetate:ethanol:triethylamine=100:10:0.5) and recrystallized from ethanol to give 1-formyl-N-[4-[[N-methyl-N-(tetrahydro-2H-pyran-4-yl)amino]methyl]phenyl]-7-[4-(3-propoxy)propoxyphenyl]-2,3-dihydro-1H-1-benzazepine-4-carboxamide (Compound 22) (304 mg, 66%) as white crystals.
Reaction SMILES: Cl[C:2]1[N:7]=[C:6]([N:8]2[CH2:13][CH2:12][O:11][CH2:10][CH2:9]2)[N:5]=[C:4]([N:14]2[C:18]3[CH:19]=[C:20]([NH:25][C:26](=[O:32])[O:27][C:28]([CH3:31])([CH3:30])[CH3:29])[CH:21]=[C:22]([O:23][CH3:24])[C:17]=3[N:16]=[C:15]2[CH:33]([F:35])[F:34])[N:3]=1.[CH3:36][N:37]([CH3:49])[CH2:38][CH2:39][S:40]([N:43]1[CH2:48][CH2:47][NH:46][CH2:45][CH2:44]1)(=[O:42])=[O:41].CCN(CC)CC>C1COCC1>[F:35][CH:33]([F:34])[C:15]1[N:14]([C:4]2[N:3]=[C:2]([N:46]3[CH2:47][CH2:48][N:43]([S:40]([CH2:39][CH2:38][N:37]([CH3:49])[CH3:36])(=[O:42])=[O:41])[CH2:44][CH2:45]3)[N:7]=[C:6]([N:8]3[CH2:13][CH2:12][O:11][CH2:10][CH2:9]3)[N:5]=2)[C:18]2[CH:19]=[C:20]([NH:25][C:26](=[O:32])[O:27][C:28]([CH3:29])([CH3:30])[CH3:31])[CH:21]=[C:22]([O:23][CH3:24])[C:17]=2[N:16]=1
Reactant: CN(C)CCS(=O)(=O)N1CCNCC1
Reactant: COc1cc(NC(=O)OC(C)(C)C)cc2c1nc(C(F)F)n2-c1nc(Cl)nc(N2CCOCC2)n1
Solvent: CCN(CC)CC
Solvent: C1CCOC1
Product: COc1cc(NC(=O)OC(C)(C)C)cc2c1nc(C(F)F)n2-c1nc(N2CCOCC2)nc(N2CCN(S(=O)(=O)CCN(C)C)CC2)n1
Temperature: 25 °C
Reaction time: 2 h
Yield: 68 %

Procedure:
A mixture of 293 mg (0.57 mmol) of tert-butyl 1-[4-chloro-6-(4-morpholinyl)-1,3,5-triazin-2-yl]-2-(difluoromethyl)-4-methoxy-1H-benzimidazol-6-yl-carbamate (Example 9), 152 mg (0.69 mmol) of N,N-dimethyl-2-(1-piperazinylsulfonyl)ethanamine (Example 83), and 87 mg (0.86 mmol) of Et3N in 20 mL THF was stirred at room temperature for 2 hrs. The solvent was removed under vacuum. After dilution with water, the residue was extracted into CH2Cl2 and dried. Removal of the solvent gave a white solid which was recrystallized from methanol to give 0.27 g, (68% yield) of tert-butyl 2-(difluoromethyl)-1-[4-(4-{[2-(dimethylamino)ethyl]sulfonyl}-1-piperazinyl)-6-(4-morpholinyl)-1,3,5-triazin-2-yl]-4-methoxy-1H-benzimidazol-6-ylcarbamate: mp 200-202° C.; 1H NMR (CDCl3) δ 8.63 (br s, 1H), 7.44 (t, JHF=53.6 Hz, 1H), 6.62 (br s, 1H), 6.36 (d, J=1.6 Hz, 1H), 4.12-3.77 (m, 15H), 3.40 (m, 4H), 3.10 (dd, J=8.2, 6.4 Hz, 2H), 2.77 (dd, J=8.2, 6.4 Hz, 2H), (s, 6H), 1.52 (s, 9H); Anal. Calcd. for C29H42F2N10O6S: C, 50.0; H, 6.1; N, 20.1. Found: C, 50.3; H, 6.15; N, 20.1%.
Reaction SMILES: [N+:1]([C:4]1[C:13]2[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=2)[CH:7]=[CH:6][C:5]=1[C:14]([C:16]1[CH:17]=[C:18]([CH:21]=[CH:22][CH:23]=1)[C:19]#[N:20])=[O:15])([O-])=O.C(O)C.O>C(O)(=O)C.[Fe]>[NH2:1][C:4]1[C:13]2[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=2)[CH:7]=[CH:6][C:5]=1[C:14]([C:16]1[CH:17]=[C:18]([CH:21]=[CH:22][CH:23]=1)[C:19]#[N:20])=[O:15]
Reactant: N#Cc1cccc(C(=O)c2ccc3ccccc3c2[N+](=O)[O-])c1
Agent: [Fe]
Solvent: CCO
Solvent: CC(=O)O
Solvent: O
Product: N#Cc1cccc(C(=O)c2ccc3ccccc3c2N)c1
Temperature: 25 °C
Reaction time: 1 h
Yield: 96.3 %

Procedure:
3-(1-nitro-2-naphthoyl)benzonitrile (6.22 g, 20.6 mmol) was dissolved at 65° C. in acetic acid (150 mL), ethanol (150 mL) and water (15 mL). After cooled to room temperature, to the solution was added iron powder (6.67 g, 119 mmol). To the mixture was stirred at 65° C. for 1 hour, and cooled to room temperature. The resultant mixture was added silica gel (100 g), filtered, and the residue was washed with ethyl acetate. The filtrate and washings were combined, washed with a saturated aqueous sodium bicarbonate solution and saturated brine. The organic layer was dried over anhydrous sodium sulfate. The solvent was removed under reduced pressure, and the residue was purified by silica gel column chromatography (chloroform), to give the titled compound as a yellow crystal (5.40 g, yield 96%).
Reaction SMILES: [Br-:1].[Br-].[Br-].C([N+](CCCC)(CCCC)CCCC)CCC.C([N+](CCCC)(CCCC)CCCC)CCC.C([N+](CCCC)(CCCC)CCCC)CCC.[CH:55]([C:58]1[CH:63]=[CH:62][CH:61]=[C:60]([CH:64]([CH3:66])[CH3:65])[C:59]=1[NH2:67])([CH3:57])[CH3:56].S([O-])([O-])(=O)=S.[Na+].[Na+]>O1CCCC1>[Br:1][C:62]1[CH:63]=[C:58]([CH:55]([CH3:57])[CH3:56])[C:59]([NH2:67])=[C:60]([CH:64]([CH3:66])[CH3:65])[CH:61]=1
Reactant: CC(C)c1cccc(C(C)C)c1N
Reactant: [Br-]
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: O=S([O-])([O-])=S
Agent: [Na+]
Solvent: C1CCOC1
Product: CC(C)c1cc(Br)cc(C(C)C)c1N
Reaction time: 2 h
Yield: 94.6 %

Procedure:
40.8 g (85 mmol) of tetra-n-butylammonium tribromide are added, at 0° C. and portionwise, to a solution of 15 g (85 mmol) of 2,6-diisopropylphenyl-amine in 200 ml of tetrahydrofuran. The medium is stirred for 2 h. It is then poured into a saturated aqueous solution of sodium thiosulphate and extracted with ethyl acetate. The organic phases are combined and washed with water. They are dried over sodium sulphate. The residue is purified by silica gel chromatography (80/20 heptane/ethyl acetate). 20.6 g of 4-bromo-2,6-diisopropylphenylamine are obtained in the form of a yellow oil (yield=95%).
Reaction SMILES: [CH:1]1([C:4]2[CH:9]=[CH:8][C:7]([S:10](Cl)(=[O:12])=[O:11])=[CH:6][CH:5]=2)[CH2:3][CH2:2]1.[F-:14].[K+]>CC(C)=O.O.CCOC(C)=O>[CH:1]1([C:4]2[CH:9]=[CH:8][C:7]([S:10]([F:14])(=[O:12])=[O:11])=[CH:6][CH:5]=2)[CH2:3][CH2:2]1
Reactant: [F-]
Reactant: O=S(=O)(Cl)c1ccc(C2CC2)cc1
Agent: [K+]
Solvent: CC(C)=O
Solvent: CCOC(C)=O
Solvent: O
Product: O=S(=O)(F)c1ccc(C2CC2)cc1
Temperature: 25 °C
Reaction time: 8 h
Yield: 79.7 %

Procedure:
Crude compound 45 (13.3 g) was dissolved in 200 mL of acetone and 60 mL of water. Potassium fluoride (7.12 g, 122 mmol) was added and the reaction mixture was stirred overnight at rt. The reaction mixture was diluted with EtOAc and washed with water. The organic layer was dried with Na2SO4, filtered, and concentrated to dryness to give 9.80 g (97%) of crude p-cyclopropyl benzenesulfonyl fluoride (Compound 46).
Reaction SMILES: C1(/C=C/C2C=CC=CC=2)C=CC=CC=1.C[N+]1([O-])CC[O:19]CC1.[CH3:23][CH2:24][C@H:25]1[C@@H:30]2[CH2:31][C@H:32]([C@@H:33](OC(C3C=CC(Cl)=CC=3)=O)[C:34]3C=CN=[C:40]4[C:35]=3[CH:36]=[C:37]([O:44]C)[CH:38]=[CH:39]4)N(CC2)C1.S(S([O-])=O)([O-])(=O)=O.[Na+].[Na+].S([O-])([O-])(=O)=O.[Na+].[Na+]>C(Cl)Cl.[Os](=O)(=O)(=O)=O.CCOCC.O>[C:35]1([CH:34]=[CH:33][C:32]2[CH:23]=[CH:24][CH:25]=[CH:30][CH:31]=2)[CH:40]=[CH:39][CH:38]=[C:37]([OH:44])[C:36]=1[OH:19]
Reactant: C[N+]1([O-])CCOCC1
Reactant: CC[C@@H]1CN2CC[C@H]1C[C@@H]2[C@@H](OC(=O)c1ccc(Cl)cc1)c1ccnc2ccc(OC)cc12
Agent: O=[Os](=O)(=O)=O
Agent: C(=C/c1ccccc1)\c1ccccc1
Agent: O=S(=O)([O-])[O-]
Solvent: ClCCl
Solvent: CCOCC
Solvent: O
Product: Oc1cccc(C=Cc2ccccc2)c1O
Temperature: 25 °C
Reaction time: 1 h

Procedure:
To a 3 L, 3-necked, round-bottomed flask equipped with a mechanical stirrer and two glass stoppers at room temperature were added E-1,2-diphenylethene (Trans-stilbene) (180.25 g, 1.0 mol, 1.0 eq), 4-methylmorpholine N-oxide (260 mL of a 60% by wt. aqueous solution (1.5 mol, 1.5 eq) dihydroquinidine 4-chlorobenzoate (23.25 g, 0.05 mol, 0.05 eq) 375 mL acetone and 7.5 mL H2O. The solution was 0.1M in alkaloid M in olefin, and the solvent was 25% water/75% acetone (v/v). The flask was immersed in a 0° C. cooling bath and stirred for 1 h. Osmium tetroxide (1.0 g, 4.0 mmol., 4.0×10-3 eq) was added in one portion producing a milky brown-yellow suspension. The reaction mixture was then stirred at 0° C. for 24 h and monitored by silica TLC (3:1 CH2Cl2 :Et2O v/v). At this point, sodium metabisulfite (285 g, 1.5 mol) was added, the mixture was diluted with 500 mL of CH2Cl2, warmed to room temperature, and stirred at room temperature for 1 h. Anhydrous sodium sulfate (50 g) was added and the mixture was stirred at room temperature overnight. The suspension was filtered through a 20 cm Buchner funnel, the filtrand was rinsed thoroughly with acetone (3×250 mL), and the filtrate was concentrated to a brown paste on a rotary evaporator with slight heating (bath temperature 30°-40° C.). The paste was dissolved in 3.5 L of EtOAc, transferred to a 6 L separatory funnel, and washed sequentially with H2O (2×500 mL), and brine (1×500 mL). The initial aqueous washes were kept separate from the subsequent acid washes which were retained for alkaloid recovery. The organic layer was dried (Na2SO4), and concentrated to give the crude diol in quantitative yield (222.7 g, 1.04 mol, 104%). The ee of the crude product was determined by 1H NMR analysis of the derived bis-Mosher ester to be 90%. One recrystallization from hot 95% acueous ethanol (3 mL/g) afforded 172-180 g (80-84%) of enantiomerically pure stilbene diol as a white solid, mp 145.5°-146.5° C.,
Reaction SMILES: C(N(CC)CC)C.[OH:8][C:9]1[CH:16]=[CH:15][C:12]([CH:13]=[O:14])=[CH:11][CH:10]=1.Cl[Si:18]([CH3:21])([CH3:20])[CH3:19]>CCOCC>[CH3:19][Si:18]([CH3:21])([CH3:20])[O:8][C:9]1[CH:16]=[CH:15][C:12]([CH:13]=[O:14])=[CH:11][CH:10]=1
Reactant: C[Si](C)(C)Cl
Reactant: O=Cc1ccc(O)cc1
Solvent: CCN(CC)CC
Solvent: CCOCC
Product: C[Si](C)(C)Oc1ccc(C=O)cc1
Reaction time: 0.25 h

Procedure:
Triethylamine (42 ml) is added dropwise to a stirred solution of 4-hydroxybenzaldehyde (33.5 g) and chlorotrimethylsilane (42 ml) in ether (300 ml). After 15 min, the mixture is filtered through diatomaceous earth and the filtrate is concentrated and distilled in vacuo, providing 4-(trimethylsiloxy)benzaldehyde as a colorless oil (43 g). This material is reacted with methoxymethyl triphenylphosphonium chloride and potassium tert-butoxide in THF, using the procedure described in Example 1 (A) above, to provide 1-(2-methoxyethenyl)-4-(trimethylsiloxy)benzene (35%) as a colorless oil after distillation in vacuo, as a mixture of (E) and (Z) isomers. This material (3.0 g) is dissolved in methanol (30 ml) containing methanesulfonic acid (0.4 ml), and the solution is refluxed for 3 hr. Sodium bicarbonate (8 ml of 1.0N solution) is added, and the mixture is concentrated in vacuo. The residue is taken up in ethyl acetate, dried, and concentrated to provide 4-[(2,2-dimethoxy)ethyl]phenol as a pale red oil (2.4 g).
Reaction SMILES: [C:1]([O:5][C:6]([C:8]1[CH:9]=[CH:10][C:11]([CH:14]=[CH:15][C:16]([O:18]CC)=[O:17])=[N:12][CH:13]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[OH-].[Na+]>C(O)C>[C:1]([O:5][C:6]([C:8]1[CH:9]=[CH:10][C:11]([CH:14]=[CH:15][C:16]([OH:18])=[O:17])=[N:12][CH:13]=1)=[O:7])([CH3:4])([CH3:2])[CH3:3]
Reactant: CCOC(=O)C=Cc1ccc(C(=O)OC(C)(C)C)cn1
Agent: [Na+]
Agent: [OH-]
Solvent: CCO
Product: CC(C)(C)OC(=O)c1ccc(C=CC(=O)O)nc1
Temperature: 25 °C
Reaction time: 5 h
Yield: 57.9 %

Procedure:
A mixture of 2.5 g of ethyl 3-(5-t-butoxycarbonyl-2-pyridyl)acrylate, 12 ml of 1N sodium hydroxide solution, and 6 ml of ethanol is stirred at room temperature for 5 hours. The ethanol is distilled off below 40° C. under reduced pressure, and the aqueous solution is adjusted to pH 4.5 with 10% hydrochloric acid. The resulting precipitate is collected and washed with cold water to give 1.3 g of the title compound.
Reaction SMILES: [CH3:1][N:2]1[C:7](Cl)=[C:6]([C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)[N:5]=[C:4]([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)[C:3]1=[O:21].COCCOC.[Li+].[N:29]1[CH:34]=[CH:33][C:32](B([O-])[O-])=[CH:31][CH:30]=1.[Li+].C(=O)([O-])[O-].[Na+].[Na+]>O>[CH3:1][N:2]1[C:7]([C:32]2[CH:33]=[CH:34][N:29]=[CH:30][CH:31]=2)=[C:6]([C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)[N:5]=[C:4]([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)[C:3]1=[O:21]
Reactant: [O-]B([O-])c1ccncc1
Reactant: Cn1c(Cl)c(-c2ccccc2)nc(-c2ccccc2)c1=O
Agent: O=C([O-])[O-]
Agent: [Li+]
Agent: [Na+]
Solvent: O
Solvent: COCCOC
Product: Cn1c(-c2ccncc2)c(-c2ccccc2)nc(-c2ccccc2)c1=O

Procedure:
To a solution of 1-methyl-3,5-diphenyl-6-chloro-1H-pyrazin-2-one (0.5 g) in 3:1 ethylene glycol dimethylether:water (30 cm3), under nitrogen, was added sequentially 4-pyridyl boronic acid lithium salt (0.42 g), sodium carbonate (0.72 g) and tetrakis-triphenylphosphine palladium (0.07 g). The reaction was heated at reflux, under nitrogen, overnight. The solvents were evaporated and the residue partitioned between water and 5% methanol/dichloromethane. The organic phase was separated, dried over magnesium sulphate and evaporated in vacuo. The residue was subjected to silica gel chromatography using 2% methanol/dichloromethane as eluant. The product was treated with hydrogen chloride in methanol and recrystallised from ethyl acetate/diethyl ether to afford1-methyl-3,5-diphenyl-6-(4-pyridyl)-1H-pyrazin-2-one hydrochloride(0.2 g; 32%) as yellow crystals. Found C, 70.50; H, 4.90; N, 11.20% C22H17N3O.HCl requires C, 70.30; H, 4.83; N, 11.18%.m/e (ES+) 340 (M+H)+.
Reaction SMILES: Cl.[NH2:2][C@@H:3]1[C:9](=[O:10])[N:8]([CH2:11][C:12]2[CH:17]=[CH:16][C:15]([CH:18]([CH3:20])[CH3:19])=[CH:14][CH:13]=2)[C:7]2[CH:21]=[CH:22][CH:23]=[CH:24][C:6]=2[O:5][CH2:4]1.[CH2:25]([O:27][C:28](=[O:51])[C@H:29](OS(C1C=CC([N+]([O-])=O)=CC=1)(=O)=O)[CH2:30][CH2:31][CH:32]1[CH2:37][CH2:36][CH2:35][CH2:34][CH2:33]1)[CH3:26].CN1CCOCC1.CN(C)C=O>CCCCCC.C(OCC)(=O)C>[CH2:25]([O:27][C:28]([C@@H:29]([NH:2][C@@H:3]1[C:9](=[O:10])[N:8]([CH2:11][C:12]2[CH:17]=[CH:16][C:15]([CH:18]([CH3:20])[CH3:19])=[CH:14][CH:13]=2)[C:7]2[CH:21]=[CH:22][CH:23]=[CH:24][C:6]=2[O:5][CH2:4]1)[CH2:30][CH2:31][CH:32]1[CH2:33][CH2:34][CH2:35][CH2:36][CH2:37]1)=[O:51])[CH3:26]
Reactant: CC(C)c1ccc(CN2C(=O)[C@@H](N)COc3ccccc32)cc1
Reactant: CCOC(=O)[C@@H](CCC1CCCCC1)OS(=O)(=O)c1ccc([N+](=O)[O-])cc1
Agent: Cl
Solvent: CCOC(C)=O
Solvent: CN(C)C=O
Solvent: CN1CCOCC1
Product: CCOC(=O)[C@H](CCC1CCCCC1)N[C@H]1COc2ccccc2N(Cc2ccc(C(C)C)cc2)C1=O

Procedure:
1.5 g of (S)-3-amino-4-oxo-5-(p-isopropylbenzyl)-2,3,4,5-tetrahydro-1,5-benzoxazepine hydrochloride, 2.93 g of (R)-alpha-[[(4-nitrophenyl)sulfonyl]oxy]-4-cyclohexylbutyric acid ethyl ester (Helv. Chim. Acta 71 (2), 337, 1988), 1.85 ml of N-methylmorpholine and 2 ml of dimethylformamide are heated at 75° C. for 3 days. The reaction mixture is concentrated and separated by means of flash chromatography (230 g of silica gel, eluant hexane/ethyl acetate 4:1). The product is obtained in the form of a colourless resin. Rf value (eluant hexane/ethyl acetate 4:1): 0.36.
Reaction SMILES: [N:1]1([CH2:6][CH2:7][NH:8][C:9]2[N:14]=[C:13]([C@@H:15]([NH:25][C:26](=[O:44])[CH2:27][N:28]3[C:36]4[C:35]([F:38])([F:37])[CH2:34][CH2:33][C:32]([F:40])([F:39])[C:31]=4[C:30]([CH:41]([F:43])[F:42])=[N:29]3)[CH2:16][C:17]3[CH:22]=[C:21]([F:23])[CH:20]=[C:19]([F:24])[CH:18]=3)[C:12]([C:45]3[CH:46]=[CH:47][C:48]([F:54])=[C:49]([CH:53]=3)[C:50]([NH2:52])=[O:51])=[CH:11][N:10]=2)[CH:5]=[CH:4]N=N1.N1(CCN)CC[CH2:57][CH2:56]1.BrC1C([C@@H](NC(=O)OC(C)(C)C)CC2C=C(F)C=C(F)C=2)=NC(S(C)(=O)=O)=NC=1>>[F:42][CH:41]([F:43])[C:30]1[C:31]2[C:32]([F:39])([F:40])[CH2:33][CH2:34][C:35]([F:38])([F:37])[C:36]=2[N:28]([CH2:27][C:26]([NH:25][C@H:15]([C:13]2[C:12]([C:45]3[CH:46]=[CH:47][C:48]([F:54])=[C:49]([CH:53]=3)[C:50]([NH2:52])=[O:51])=[CH:11][N:10]=[C:9]([NH:8][CH2:7][CH2:6][N:1]3[CH2:57][CH2:56][CH2:4][CH2:5]3)[N:14]=2)[CH2:16][C:17]2[CH:18]=[C:19]([F:24])[CH:20]=[C:21]([F:23])[CH:22]=2)=[O:44])[N:29]=1
Reactant: NCCN1CCCC1
Reactant: NC(=O)c1cc(-c2cnc(NCCn3ccnn3)nc2[C@H](Cc2cc(F)cc(F)c2)NC(=O)Cn2nc(C(F)F)c3c2C(F)(F)CCC3(F)F)ccc1F
Agent: CC(C)(C)OC(=O)N[C@@H](Cc1cc(F)cc(F)c1)c1nc(S(C)(=O)=O)ncc1Br
Product: NC(=O)c1cc(-c2cnc(NCCN3CCCC3)nc2[C@H](Cc2cc(F)cc(F)c2)NC(=O)Cn2nc(C(F)F)c3c2C(F)(F)CCC3(F)F)ccc1F

Procedure:
The title compound (27) was prepared according to the method presented for the synthesis of compound 23F of Example 23 starting with 2-(pyrrolidin-1-yl)ethanamine and 23B. 1H NMR (400 MHz, CD3OD) δ 8.67 (d, J=7.8 Hz, 1H), 8.05 (s, 1H), 7.41-7.23 (m, 2H), 7.13 (dd, J=10.7, 8.5 Hz, 1H), 6.95-6.48 (m, 2H), 6.35 (d, J=6.2 Hz, 2H), 5.15 (m, 1H), 4.95 (q, J=16.7 Hz, 2H), 3.74 (m, 4H), 3.43 (m, 2H), 3.11 (m, 2H), 3.00-2.88 (m, 2H), 2.70-2.28 (m, 4H), 2.13-1.89 (m, 4H). MS (m/z) 769.29 [M+H]+.
Reaction SMILES: [CH2:1]([OH:6])[CH2:2][CH:3]([OH:5])[CH3:4].[F:7][C:8]1[C:13]([S:14](Cl)(=[O:16])=[O:15])=[C:12]([F:18])[C:11]([F:19])=[C:10]([F:20])[C:9]=1[F:21].C([O-])(O)=O.[Na+].C(OCC)(=O)C>C(Cl)Cl>[F:7][C:8]1[C:9]([F:21])=[C:10]([F:20])[C:11]([F:19])=[C:12]([F:18])[C:13]=1[S:14]([O:6][CH2:1][CH2:2][CH:3]([OH:5])[CH3:4])(=[O:16])=[O:15]
Reactant: CC(O)CCO
Reactant: O=S(=O)(Cl)c1c(F)c(F)c(F)c(F)c1F
Agent: O=C([O-])O
Agent: [Na+]
Solvent: ClCCl
Solvent: CCOC(C)=O
Product: CC(O)CCOS(=O)(=O)c1c(F)c(F)c(F)c(F)c1F
Temperature: 25 °C
Reaction time: 6 h
Yield: 40.6 %

Procedure:
To a solution of 1,3-butane diol (0.9 g, 10 mmol) and TEA (0.61 g, 6 mmol) in CH2Cl2 (4 mL) at 0° C. was added pentafluorobenzenesulfonyl chloride (0.53 g, 2 mmol) dissolved in CH2Cl2 (4 mL). The solution was stirred for 6 h over which time the solution slowly warmed to rt. Saturated aqueous NaHCO3 (25 mL) was added to the solution and the mixture was stirred at rt for 30 min. The organics were extracted with CH2Cl2 (50 mL) and washed with 0.5 M HCl (3×20 mL), saturated aqueous NaHCO3 (1×20 mL) and saturated aqueous NaCl (1×20 mL). The organics were dried over Na2SO4 and concentrated to give a crude mixture. Silica gel chromatography with ethyl acetate in hexanes yielded the desired product (0.26 g, 40%). 1H NMR (400 MHz CDCl3) δ 4.62 (m, 2H), 4.13 (m, 1H), 2.11 (m, 1H), 1.94 (m, 1H), 1.40 (d, 3H, J=6.2 Hz). Anal. Calcd. For C10H9F5O4S: C, 37.51; H, 2.83. Found: C, 37.70; H, 2.93.
Reaction SMILES: O1CCCCC1[O:7][C@@H:8]([CH2:38][CH2:39][CH2:40][CH2:41][CH3:42])[CH2:9][CH2:10][CH2:11][C:12]([CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH2:32][C:33]([O:35][CH2:36][CH3:37])=[O:34])([C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14].O1CCCC1.Cl>O.CCOCC>[OH:7][C@@H:8]([CH2:38][CH2:39][CH2:40][CH2:41][CH3:42])[CH2:9][CH2:10][CH2:11][C:12]([CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH2:32][C:33]([O:35][CH2:36][CH3:37])=[O:34])([C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[C:13]([O:15][C:16]([CH3:18])([CH3:19])[CH3:17])=[O:14]
Reactant: CCCCC[C@@H](CCCC(CCCCCCC(=O)OCC)(C(=O)OC(C)(C)C)C(=O)OC(C)(C)C)OC1CCCCO1
Agent: Cl
Solvent: CCOCC
Solvent: O
Solvent: C1CCOC1
Product: CCCCC[C@H](O)CCCC(CCCCCCC(=O)OCC)(C(=O)OC(C)(C)C)C(=O)OC(C)(C)C
Reaction time: 6 h

Procedure:
Di-tert.-butyl 2-[4(S)-(2-tetrahydropyranyloxy)nonyl]-2-(6-ethoxycarbonylhexyl)malonate (47.8 g., 0.08 mole) is added to a mixture of tetrahydrofuran (300 ml.) and 6N hydrochloric acid (15 ml.). The resulting solution is allowed to stand at room temperature for 6 hours. The solution is then diluted with 1.5 liters of water. The oily product is taken up in ether, washed with four portions of water, and with brine and dried over sodium sulfate. Distillation of the ether in vacuo leaves the title compound as a residual oil weighing 39.5 g.
Reaction SMILES: [CH2:1]([O:8][C:9]([C:11]1[NH:12][C:13]([CH:16]=[O:17])=[CH:14][CH:15]=1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH2:18](OC(C1NC(C(O)=O)=CC=1)=O)C1C=CC=CC=1.C(=O)([O-])[O-].[Cs+].[Cs+].CI>CN(C=O)C.O>[CH:16]([C:13]1[N:12]([CH3:18])[C:11]([C:9]([O:8][CH2:1][C:2]2[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=2)=[O:10])=[CH:15][CH:14]=1)=[O:17]
Reactant: O=Cc1ccc(C(=O)OCc2ccccc2)[nH]1
Reactant: O=C(O)c1ccc(C(=O)OCc2ccccc2)[nH]1
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: O
Solvent: CI
Solvent: CN(C)C=O
Product: Cn1c(C=O)ccc1C(=O)OCc1ccccc1
Temperature: 25 °C
Reaction time: 2 h

Procedure:
To a stirred solution of 5-formyl-1H-pyrrole-2-carboxylic acid benzyl ester (from the preparation of Intermediate 18) (400 mg, 1.75 mmol) in DMF (10 mL) is added cesium carbonate (853 mg, 2.62 mmol) and MeI (297 mg, 2.09 mmol). The mixture is stirred at room temperature for 2 hours then water is added and the mixture is extracted with ethyl acetate (3×). The combined organic layers are washed with water and brine then is dried over magnesium sulfate. The solvent is removed under reduced pressure to give benzyl 5-formyl-1-methyl-1H-pyrrole-2-carboxylate; HPLC Retention time 1.26 minutes (condition C): MS 244.3 (M+1).
Reaction SMILES: [NH2:1][C:2]1[N:7]=[C:6]([NH2:8])[C:5]([C:9]2[CH:14]=[C:13]([N+]([O-])=O)[CH:12]=[CH:11][C:10]=2[Cl:18])=[C:4]([CH3:19])[N:3]=1.N([O-])=O.[Na+].[CH3:24][SH:25]>[Cu]>[NH2:1][C:2]1[N:7]=[C:6]([NH2:8])[C:5]([C:9]2[CH:14]=[C:13]([S:25][CH3:24])[CH:12]=[CH:11][C:10]=2[Cl:18])=[C:4]([CH3:19])[N:3]=1
Reactant: Cc1nc(N)nc(N)c1-c1cc([N+](=O)[O-])ccc1Cl
Reactant: CS
Agent: [Cu]
Agent: O=N[O-]
Agent: [Na+]
Product: CSc1ccc(Cl)c(-c2c(C)nc(N)nc2N)c1

Procedure:
This compound was prepared in a similar manner to the compound of Example 54 by reaction of the diazonium salt with methanethiol in the presence of copper powder, mp. 194°-198° C.