Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: Cl[C:2]1[N:7]2[N:8]=[C:9]([CH3:11])[CH:10]=[C:6]2[N:5]=[C:4]([NH:12][C:13](=[O:24])[C:14]2[CH:19]=[CH:18][C:17]([C:20]([OH:23])([CH3:22])[CH3:21])=[CH:16][CH:15]=2)[CH:3]=1.[NH:25]1[CH2:30][CH2:29][CH:28]([NH:31][C:32](=[O:38])[O:33][C:34]([CH3:37])([CH3:36])[CH3:35])[CH2:27][CH2:26]1.C(N(C(C)C)CC)(C)C>CN1CCCC1=O>[OH:23][C:20]([C:17]1[CH:18]=[CH:19][C:14]([C:13]([NH:12][C:4]2[CH:3]=[C:2]([N:25]3[CH2:26][CH2:27][CH:28]([NH:31][C:32](=[O:38])[O:33][C:34]([CH3:36])([CH3:35])[CH3:37])[CH2:29][CH2:30]3)[N:7]3[N:8]=[C:9]([CH3:11])[CH:10]=[C:6]3[N:5]=2)=[O:24])=[CH:15][CH:16]=1)([CH3:22])[CH3:21]
Reactant: Cc1cc2nc(NC(=O)c3ccc(C(C)(C)O)cc3)cc(Cl)n2n1
Reactant: CC(C)(C)OC(=O)NC1CCNCC1
Solvent: CCN(C(C)C)C(C)C
Solvent: CN1CCCC1=O
Product: Cc1cc2nc(NC(=O)c3ccc(C(C)(C)O)cc3)cc(N3CCC(NC(=O)OC(C)(C)C)CC3)n2n1
Temperature: 100 °C
Yield: 0.1 %

Procedure:
In a 100 mL round-bottomed flask were placed N-(7-chloro-2-methylpyrazolo[1,5-a]pyrimidin-5-yl)-4-(2-hydroxypropan-2-yl)benzamide (2F, 0.5 g, 1.450 mmol) and tert-butyl piperidin-4-ylcarbamate (0.305 g, 1.523 mmol) in N-methyl-2-pyrrolidinone (Volume: 14.50 ml). Diisopropylethylamine (0.253 ml, 1.450 mmol) was added. The reaction was heated overnight at 100° C. The reaction mixture was partitioned between ethyl acetate and brine. The organic was dried MgSO4, filtered and concentrated in vacuo. The compound was chromatographed on silica using 30-50% EtOAc/Hexane silica column to give tert-butyl 1-(5-(4-(2-hydroxypropan-2-yl)benzamido)-2-methylpyrazolo[1,5-a]pyrimidin-7-yl)piperidin-4-ylcarbamate (6A, 0.576 mg, 78%) as a yellow solid. 1H NMR (METHANOL-d4) δ: 7.79-8.02 (m, 2H), 7.60-7.73 (m, 2H), 7.33 (s, 1H), 6.83 (br. s., 1H), 6.13 (s, 1H), 4.39 (d, J=12.6 Hz, 2H), 3.57-3.78 (m, 1H), 3.11-3.23 (m, 2H), 2.43 (s, 3H), 1.73 (d, J=8.8 Hz, 2H), 1.56 (s, 6H), 1.46 (s, 9H); resonances of the three piperidine peaks are obscured by diisopropylethylamine. ESI-MS: m/z 509.0 (M+H)+.
Reaction SMILES: [C:1]([O:5][C:6]([N:8]1[CH2:17][CH2:16][C:15]2[C:10](=[C:11]([C:18](=[O:34])[NH:19][C:20]3([C:29]([O:31]CC)=[O:30])[CH2:28][C:27]4[C:22](=[CH:23][CH:24]=[CH:25][CH:26]=4)[CH2:21]3)[CH:12]=[CH:13][CH:14]=2)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[OH-].[K+].O>CCO>[C:1]([O:5][C:6]([N:8]1[CH2:17][CH2:16][C:15]2[C:10](=[C:11]([C:18](=[O:34])[NH:19][C:20]3([C:29]([OH:31])=[O:30])[CH2:28][C:27]4[C:22](=[CH:23][CH:24]=[CH:25][CH:26]=4)[CH2:21]3)[CH:12]=[CH:13][CH:14]=2)[CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]
Reactant: CCOC(=O)C1(NC(=O)c2cccc3c2CN(C(=O)OC(C)(C)C)CC3)Cc2ccccc2C1
Agent: [K+]
Agent: [OH-]
Solvent: CCO
Solvent: O
Product: CC(C)(C)OC(=O)N1CCc2cccc(C(=O)NC3(C(=O)O)Cc4ccccc4C3)c2C1
Temperature: 25 °C
Reaction time: 3 h
Yield: 60.5 %

Procedure:
The product (217) (2.46 g, 5.3 mmol) and KOH (2.5 g, 45 mmol) is dissolved in EtOH (20 mL) and water (1 mL) under a water bath. The water bath is removed when the KOH is completely dissolved and the resulting reaction solution is stirred at RT for 3 h. After concentration in vacuo, the residue is dissolved in water (50 mL) and acidified with conc. HCl until no more white precipitate came out of the water. The precipitate is filtered to give a pure product (218) as white solid (1.4 g, 61%).
Reaction SMILES: [C:1]([OH:7])(=[O:6])[CH2:2][C:3](O)=O.[F:8][C:9]1[CH:16]=[C:15]([O:17][CH2:18][C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][N:20]=2)[CH:14]=[CH:13][C:10]=1C=O.N1CCCCC1.Cl>O.N1C=CC=CC=1>[F:8][C:9]1[CH:16]=[C:15]([O:17][CH2:18][C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][N:20]=2)[CH:14]=[CH:13][C:10]=1/[CH:3]=[CH:2]/[C:1]([OH:7])=[O:6]
Reactant: O=Cc1ccc(OCc2ccccn2)cc1F
Reactant: O=C(O)CC(=O)O
Agent: Cl
Solvent: C1CCNCC1
Solvent: O
Solvent: c1ccncc1
Product: O=C(O)/C=C/c1ccc(OCc2ccccn2)cc1F
Temperature: 75 °C
Reaction time: 1.5 h
Yield: 84.6 %

Procedure:
To 1.8 g of malonic acid were added 18 mL of pyridine, 2.0 g of 2-fluoro-4-(2-pyridylmethoxy)benzaldehyde and 0.21 mL of piperidine. The mixture was stirred at 75° C. for 1.5 hours and further stirred at 95° C. for 1 hour. The reaction mixture was cooled with ice, water was added thereto, and 10% hydrochloric acid was added to adjust the pH to 4. The resulting precipitate was separated by filtration to give 2.0 g of the title compound (85% yield).
Reaction SMILES: Cl.[F:2][C:3]1[CH:13]=[CH:12][C:6]([C:7](=[NH:11])OCC)=[CH:5][CH:4]=1.[CH2:14]([O:16][CH:17]([O:20][CH2:21][CH3:22])[CH2:18][NH2:19])[CH3:15]>C(O)C>[CH2:14]([O:16][CH:17]([O:20][CH2:21][CH3:22])[CH2:18][NH:19][C:7](=[NH:11])[C:6]1[CH:5]=[CH:4][C:3]([F:2])=[CH:13][CH:12]=1)[CH3:15]
Reactant: CCOC(CN)OCC
Reactant: CCOC(=N)c1ccc(F)cc1
Agent: Cl
Solvent: CCO
Product: CCOC(CNC(=N)c1ccc(F)cc1)OCC
Reaction time: 8 h

Procedure:
To a solution of ethyl 4-fluorobenzimidate hydrochloride (18.5 g) in ethanol (90 mL) at 0° C. was added aminoacetaldehyde diethyl acetal (14.5 mL) and the resulting solution was kept at 5° C. overnight. The solvent was evaporated, the resulting oil was dissolved in 1N sodium hydroxide (200 mL), and the solution was extracted with dichloromethane. The organic extracts were dried and evaporated to yield N-(2,2-diethoxyethyl)-4-fluorobenzamidine as an oil (21 g); MS: m/z=255(M+1).
Reaction SMILES: [C:1]([NH:9][CH2:10][C:11]([C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1)=O)(=O)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.P12(SP3(SP(SP(S3)(S1)=S)(=S)S2)=S)=[S:20]>>[C:2]1([C:1]2[S:20][C:11]([C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=3)=[CH:10][N:9]=2)[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: O=C(CNC(=O)c1ccccc1)c1ccccc1
Reactant: S=P12SP3(=S)SP(=S)(S1)SP(=S)(S2)S3
Product: c1ccc(-c2cnc(-c3ccccc3)s2)cc1

Procedure:
Another sample of 2,5-diphenylthiazole is prepared by reacting alpha-(benzamido) acetophenone with phosphorus pentasulfide according to the procedure given by Gabriel, Berichte 43, 137 (1910); C.A. 4, 928. The overall yield, based on phenacyl bromide, is about 25% and the product melts at 103°-106° C.
Reaction SMILES: [C:1]1([CH3:9])[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[Mg]Cl.[CH3:10][O:11][C:12]([C:14]1[CH2:15][N:16]([C:28]([O:30][C:31]([CH3:34])([CH3:33])[CH3:32])=[O:29])[CH2:17][CH2:18][C:19]=1OS(C(F)(F)F)(=O)=O)=[O:13]>C1COCC1.[Cl-].[Zn+2].[Cl-].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>[CH3:10][O:11][C:12]([C:14]1[CH2:15][N:16]([C:28]([O:30][C:31]([CH3:34])([CH3:33])[CH3:32])=[O:29])[CH2:17][CH2:18][C:19]=1[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][C:1]=1[CH3:9])=[O:13]
Reactant: Cc1ccccc1[Mg]Cl
Reactant: COC(=O)C1=C(OS(=O)(=O)C(F)(F)F)CCN(C(=O)OC(C)(C)C)C1
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: [Cl-]
Agent: [Zn+2]
Solvent: C1CCOC1
Product: COC(=O)C1=C(c2ccccc2C)CCN(C(=O)OC(C)(C)C)C1
Temperature: 25 °C
Reaction time: 6 h

Procedure:
To a 1 M solution of o-tolylmagnesium chloride in THF (6.26 ml, 41.5 mmol) was added dropwise a freshly prepared solution of dried zinc chloride (8.48 g, 62.2 mmol) in dry THF (200 ml) at 0° C. After completed addition the reaction mixture was allowed to slowly warm to room temperature over a period of 1 h. To this mixture were added a solution of 4-trifluoromethanesulfonyloxy-5,6-dihydro-2H-pyridine-1,3-dicarboxylic acid 1-tert-butyl ester 3-methyl ester (10.7 g, 27.5 mmol) in THF (270 ml) and tetrakis(triphenylphosphine)palladium(0) (0.96 g, 0.83 mmol). After stirring for 6 h at room temperature the reaction was quenched with ice. The mixture was diluted with tert-butyl methyl ether and washed with 2 M aqueous sodium carbonate solution. The aqueous layer was extracted with two portions of tert-butyl methyl ether.
Reaction SMILES: [Cl:1][N:2]1[C:7](=[O:8])[N:6](Cl)[C:5](=[O:10])[N:4](Cl)[C:3]1=[O:12].[OH2:13]>>[Cl:1][OH:13].[NH:2]1[C:7](=[O:8])[NH:6][C:5](=[O:10])[NH:4][C:3]1=[O:12]
Reactant: O
Reactant: O=c1n(Cl)c(=O)n(Cl)c(=O)n1Cl
Product: O=c1[nH]c(=O)[nH]c(=O)[nH]1
Product: OCl

Procedure:
In moisture, trichloroisocyanuric acid is slightly soluble (1.5-2 gr/100 gr H2O) and gives off hypochlorous acid, mono and di-chloroisocyanuric acid and isocyanuric acid.
Reaction SMILES: C(N(CC)CC)C.F[C:9]1[CH:17]=[CH:16][C:15]([CH2:18][C:19]2[C:28]3[C:23](=[CH:24][CH:25]=[CH:26][CH:27]=3)[C:22](=[O:29])[NH:21][N:20]=2)=[CH:14][C:10]=1[C:11]([OH:13])=O.Cl.[CH:31]1([O:36][CH:37]2[CH2:42][CH2:41][NH:40][CH2:39][CH2:38]2)[CH2:35][CH2:34][CH2:33][CH2:32]1.F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2C=CC=CC=2N=N1>CC(N(C)C)=O>[CH:31]1([O:36][CH:37]2[CH2:42][CH2:41][N:40]([C:11]([C:10]3[CH:14]=[C:15]([CH:16]=[CH:17][CH:9]=3)[CH2:18][C:19]3[C:28]4[C:23](=[CH:24][CH:25]=[CH:26][CH:27]=4)[C:22](=[O:29])[NH:21][N:20]=3)=[O:13])[CH2:39][CH2:38]2)[CH2:35][CH2:34][CH2:33][CH2:32]1
Reactant: C1CCC(OC2CCNCC2)C1
Reactant: O=C(O)c1cc(Cc2n[nH]c(=O)c3ccccc23)ccc1F
Agent: CN(C)C(On1nnc2ccccc21)=[N+](C)C
Agent: Cl
Agent: F[P-](F)(F)(F)(F)F
Solvent: CC(=O)N(C)C
Solvent: CCN(CC)CC
Product: O=C(c1cccc(Cc2n[nH]c(=O)c3ccccc23)c1)N1CCC(OC2CCCC2)CC1
Temperature: 20 °C
Reaction time: 72 h
Yield: 39.2 %

Procedure:
Triethylamine (0.298 ml, 2.14 mmol) was added in one portion to 3-((4-oxo-3,4-dihydrophthalazin-1-yl)methyl)benzoic acid (1b) (200 mg, 0.71 mmol), 4-(cyclopentyloxy)piperidine hydrochloride (121 mg, 0.71 mmol) and O-benzotriazol-1-yl-N,N,N′,N′-tetra-methyluronium hexafluorophosphate (352 mg, 0.93 mmol) in DMA (2 ml) at 20° C. under air. The resulting mixture was stirred at 20° C. for 3 days. The crude product was purified by preparative HPLC (Waters XBridge Prep C18 OBD column, 5μ silica, 19 mm diameter, 100 mm length), using decreasingly polar mixtures of water (containing 1% NH3) and MeCN as eluents. Fractions containing the desired compound were evaporated to dryness to afford the desired material as a white solid (120 mg, 39% yield); 1H NMR (400.132 MHz, DMSO) δ 1.22-1.86 (11H, m), 3.00-3.20 (2H, m), 3.25-3.43 (2H, m), 3.52-3.56 (1H, m), 3.91-4.05 (2H, m), 4.35 (2H, s), 7.20 (1H, d), 7.31 (1H, s), 7.34-7.40 (2H, m), 7.80-7.89 (2H, m), 7.96 (1H, d), 8.26 (1H, d), 12.57 (1H, s); m/z (LC-MS, ESI+), RT=2.18 (M+H 432.1)
Reaction SMILES: C([O:4][CH:5]([CH3:23])[C:6]([NH:8][C:9]1[CH:14]=[CH:13][C:12]([C:15]2[CH:16]([CH3:22])[NH:17][C:18](=[O:21])[NH:19][N:20]=2)=[CH:11][CH:10]=1)=[O:7])(=O)C.[OH-].[Na+].O>CO>[C:6]([NH:8][C:9]1[CH:10]=[CH:11][C:12]([C:15]2[CH:16]([CH3:22])[NH:17][C:18](=[O:21])[NH:19][N:20]=2)=[CH:13][CH:14]=1)(=[O:7])[CH:5]([CH3:23])[OH:4]
Reactant: CC(=O)OC(C)C(=O)Nc1ccc(C2=NNC(=O)NC2C)cc1
Agent: [Na+]
Agent: [OH-]
Solvent: O
Solvent: CO
Product: CC(O)C(=O)Nc1ccc(C2=NNC(=O)NC2C)cc1
Reaction time: 0.25 h
Yield: 74.8 %

Procedure:
To a stirred solution of 6-[4-(2-acetoxypropionylamino)phenyl]-5-methyl-4,5-dihydro-1,2,4-triazin-3(2H)-one (0.94 g) in methanol (6 ml) was added dropwise 1N sodium hydroxide (3 ml) under ice cooling. The mixture was stirred for 15 minutes after adding water. The resulting precipitates were collected by filtration, washed with water and dried to give 0.61 g of 6-(4-lactoylaminophenyl)-5-methyl-4,5-dihydro-1,2,4-triazin-3(2H)-one.
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]([F:11])([F:10])[F:9])=[CH:4][C:3]=1[NH:12][C:13]([C:15]1[CH:16]=[CH:17][C:18]([CH3:25])=[C:19]([CH:24]=1)[C:20]([O:22]C)=[O:21])=[O:14].C1COCC1.[OH-].[Li+]>O>[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]([F:11])([F:10])[F:9])=[CH:4][C:3]=1[NH:12][C:13]([C:15]1[CH:16]=[CH:17][C:18]([CH3:25])=[C:19]([CH:24]=1)[C:20]([OH:22])=[O:21])=[O:14]
Reactant: COC(=O)c1cc(C(=O)Nc2cc(C(F)(F)F)ccc2F)ccc1C
Agent: [Li+]
Agent: [OH-]
Solvent: C1CCOC1
Solvent: O
Product: Cc1ccc(C(=O)Nc2cc(C(F)(F)F)ccc2F)cc1C(=O)O
Temperature: 25 °C

Procedure:
A solution of methyl 5-((2-fluoro-5-(trifluoromethyl)phenyl)carbamoyl)-2-methylbenzoate 35 (0.904 g, 2.5 mmol), THF (20 mL), lithium hydroxide (0.18 g, 7.6 mmol), and water (5 mL) was heated at 55° C. for 24 hours and then cooled to room temperature. The aqueous layer was separated, cooled in an ice-water bath, and acidified with 6 M HCl (aq) to pH 1. This solution was extracted with ethyl acetate (3×10 mL), and the combined organic phases were dried over anhydrous sodium sulfate, filtered, and concentrated to afford 5-((2-fluoro-5-(trifluoromethyl)phenyl)carbamoyl)-2-methylbenzoic acid 36. MS m/z found 342 [MH+]; calc. for C16H11F4NO3=341.26.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([OH:9])[CH:5]=[CH:6][C:7]=1[Cl:8].Cl[CH2:11][C:12]1[CH:17]=[C:16]([N+:18]([O-:20])=[O:19])[CH:15]=[C:14]([N+:21]([O-:23])=[O:22])[CH:13]=1>C(O)CCC>[Cl:1][C:2]1[CH:3]=[C:4]([CH:5]=[CH:6][C:7]=1[Cl:8])[O:9][CH2:11][C:12]1[CH:13]=[C:14]([N+:21]([O-:23])=[O:22])[CH:15]=[C:16]([N+:18]([O-:20])=[O:19])[CH:17]=1
Reactant: Oc1ccc(Cl)c(Cl)c1
Reactant: O=[N+]([O-])c1cc(CCl)cc([N+](=O)[O-])c1
Solvent: CCCCO
Product: O=[N+]([O-])c1cc(COc2ccc(Cl)c(Cl)c2)cc([N+](=O)[O-])c1

Procedure:
0.5 mmole 3,4-Dichloro-phenol and 1 mmole KI were added to a solution of 0.5 mmole 1-Chloromethyl-3,5-dinitrobenzene in 2.5 ml 1-Butanol. The mixture was stirred under reflux overnight. After evaporation the 1-Butanol, the residue was washed with 2×10 ml 1 N HCl and 2×10 ml EtOAc, and dried. 1H NMR (DMSO-d6, 400 MHz) 5.44 (s, 2H); 7.14 (d, 1H); 7.43 (s, 1H); 7.58 (d, 1H); 8.73 (s, 2H); 8.81 (s, 1H);
Reaction SMILES: CCCC[N+](CCCC)(CCCC)CCCC.[F-].[N:19]([CH2:22][C@@H:23]([C:32]1[CH:41]=[CH:40][C:39]([O:42][CH2:43][C:44]2[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=2)=[C:38]2[C:33]=1[CH:34]=[CH:35][C:36](=[O:50])[NH:37]2)[O:24][Si](C(C)(C)C)(C)C)=[N+:20]=[N-:21]>C1COCC1>[N:19]([CH2:22][C@@H:23]([C:32]1[CH:41]=[CH:40][C:39]([O:42][CH2:43][C:44]2[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=2)=[C:38]2[C:33]=1[CH:34]=[CH:35][C:36](=[O:50])[NH:37]2)[OH:24])=[N+:20]=[N-:21]
Reactant: CC(C)(C)[Si](C)(C)O[C@@H](CN=[N+]=[N-])c1ccc(OCc2ccccc2)c2[nH]c(=O)ccc12
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: [F-]
Solvent: C1CCOC1
Product: [N-]=[N+]=NC[C@H](O)c1ccc(OCc2ccccc2)c2[nH]c(=O)ccc12
Yield: 91.9 %

Procedure:
TBAF (1.0 M in THF, 0.443 mL, 0.443 mmol) was added to a stirring solution of Intermediate 1 (200 mg, 0.443 mmol) in THF (4 mL) at rt. The resulting mixture was stirred over night then concentrated. Chromatography (1:3, Hexanes/EtOAc) afforded the title compound (137 mg, 92%) as an off-white solid. ES/MS calcd. for C18H17N4O3+ 337.1. found m/z=337.2 (M+H)+.
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]([NH2:9])[C:5]([Cl:8])=[N:6][CH:7]=1.C(N(C(C)C)CC)(C)C.CO[C:21]1[CH:22]=[C:23]([CH:27]=[CH:28][CH:29]=1)[C:24](Cl)=[O:25].[C:30](OCC)(=[O:32])C>ClCCl>[Br:1][C:2]1[CH:3]=[C:4]([NH:9][C:24](=[O:25])[C:23]2[CH:22]=[CH:21][C:29]([O:32][CH3:30])=[CH:28][CH:27]=2)[C:5]([Cl:8])=[N:6][CH:7]=1
Reactant: Nc1cc(Br)cnc1Cl
Reactant: COc1cccc(C(=O)Cl)c1
Reactant: CCOC(C)=O
Solvent: ClCCl
Solvent: CCN(C(C)C)C(C)C
Product: COc1ccc(C(=O)Nc2cc(Br)cnc2Cl)cc1
Yield: 92 %

Procedure:
5-Bromo-2-chloropyridin-3-amine (1.5 g, 7.23 mmol) was dissolved in dichloromethane (30 ml). Diisopropylethylamine (1.52 ml, 8.67 mmol) first and then a solution of 3-methoxybenzoyl chloride (1.08 ml, 7.95 mmol) in dichloromethane (20 ml) were added. After 1 h at room temperature the reaction mixture was diluted with ethyl acetate and washed with water and brine, dried over sodium sulphate, filtered and evaporated under reduced pressure to give 2.8 g (92% yield) of the title compound. Purity 81%.
Reaction SMILES: [OH:1][C:2]1[C:11]2[C:6](=[CH:7][C:8]([CH2:12][C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=3)=[CH:9][N:10]=2)[NH:5][C:4](=[O:19])[C:3]=1[C:20](OCC)=[O:21].[CH2:25]([NH2:31])[C:26]1[O:30][CH:29]=[CH:28][CH:27]=1>>[O:30]1[CH:29]=[CH:28][CH:27]=[C:26]1[CH2:25][NH:31][C:20]([C:3]1[C:4](=[O:19])[NH:5][C:6]2[C:11]([C:2]=1[OH:1])=[N:10][CH:9]=[C:8]([CH2:12][C:13]1[CH:14]=[CH:15][CH:16]=[CH:17][CH:18]=1)[CH:7]=2)=[O:21]
Reactant: NCc1ccco1
Reactant: CCOC(=O)c1c(O)c2ncc(Cc3ccccc3)cc2[nH]c1=O
Product: O=C(NCc1ccco1)c1c(O)c2ncc(Cc3ccccc3)cc2[nH]c1=O

Procedure:
This compound was prepared from ethyl 4-hydroxy-2-oxo-7-(phenylmethyl)-1,2-dihydro-1,5-naphthyridine-3-carboxylate and furfurylamine employing methods similar to those described in Example 2 and was obtained as a white solid; 1H NMR (d6-DMSO) δ 12.13 (1H, br), 11.12 (1H, br), 10.15 (1H, br), 8.20 (1H, br s), 7.57 (1H, s), 7.31-7.20 (6H, m), 6.38 (1H, s), 6.27 (1H, br s), 4.48 (2H, br), 4.01 (2H, br s); HRMS calcd for C21H17N3O4+H+: 376.1297. Found: 376.1286.
Reaction SMILES: [Cl:1][C:2]1[C:32]([C:33]([F:36])([F:35])[F:34])=[CH:31][CH:30]=[CH:29][C:3]=1[CH2:4][N:5]([CH2:20][CH:21]([OH:28])[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1)[CH2:6][CH2:7][CH2:8][O:9][C:10]1[CH:11]=[C:12]([CH2:16][C:17]([OH:19])=[O:18])[CH:13]=[CH:14][CH:15]=1.[C:37](O)(=[O:39])[CH3:38].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.CC(OC(/N=N/C(OC(C)C)=O)=O)C>C1(C)C=CC=CC=1>[Cl:1][C:2]1[C:32]([C:33]([F:34])([F:35])[F:36])=[CH:31][CH:30]=[CH:29][C:3]=1[CH2:4][N:5]([CH2:20][CH:21]([O:28][C:37](=[O:39])[CH3:38])[C:22]1[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=1)[CH2:6][CH2:7][CH2:8][O:9][C:10]1[CH:11]=[C:12]([CH2:16][C:17]([OH:19])=[O:18])[CH:13]=[CH:14][CH:15]=1
Reactant: O=C(O)Cc1cccc(OCCCN(Cc2cccc(C(F)(F)F)c2Cl)CC(O)c2ccccc2)c1
Reactant: CC(=O)O
Agent: CC(C)OC(=O)/N=N/C(=O)OC(C)C
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: Cc1ccccc1
Product: CC(=O)OC(CN(CCCOc1cccc(CC(=O)O)c1)Cc1cccc(C(F)(F)F)c1Cl)c1ccccc1
Temperature: 0 °C
Yield: 75 %

Procedure:
A solution of 2-(3-{3-[[2-chloro-3-(trifluoromethyl)benzyl](2-hydroxy-2-phenyl-ethyl)amino]propoxy}-phenyl)acetic acid (Example 15 b) in anhydrous toluene (5 ml) was treated with acetic acid (3 mg). Polymer bound triphenylphosphine (30 mg, 3 mmol/g) was then added, and the mixture reacted for 15 min. The reaction mixture was then cooled to 0° C. and diisopropylazodicarboxylate(10 mg, 0.05 mmol) was added dropwise. After stirring at RT overnight the crude mixture was filtered and the solid washed with 10 ml toluene. After concentration of the filtrate in vacuo, the crude product was purified by HPLC to give the title compound as an oil (20 mg, 75%). MS (ESI) 563.8 (M+H)+.
Reaction SMILES: [C:1]([O:5][C:6](=[O:34])[NH:7][C@H:8]1[CH2:12][CH2:11][C@H:10]([N:13]2[C:24]3[C:16](=[CH:17][N:18]=[C:19]4[C:23]=3[CH:22]=[CH:21][N:20]4S(C3C=CC=CC=3)(=O)=O)[N:15]=[N:14]2)[CH2:9]1)([CH3:4])([CH3:3])[CH3:2].[OH-].[Na+].CO.C1COCC1>C(Cl)Cl>[C:1]([O:5][C:6](=[O:34])[NH:7][C@H:8]1[CH2:12][CH2:11][C@H:10]([N:13]2[C:24]3[C:16](=[CH:17][N:18]=[C:19]4[C:23]=3[CH:22]=[CH:21][NH:20]4)[N:15]=[N:14]2)[CH2:9]1)([CH3:4])([CH3:2])[CH3:3]
Reactant: CC(C)(C)OC(=O)N[C@H]1CC[C@H](n2nnc3cnc4c(ccn4S(=O)(=O)c4ccccc4)c32)C1
Agent: [Na+]
Agent: [OH-]
Solvent: C1CCOC1
Solvent: CO
Solvent: ClCCl
Product: CC(C)(C)OC(=O)N[C@H]1CC[C@H](n2nnc3cnc4[nH]ccc4c32)C1
Temperature: 25 °C
Reaction time: 0.75 h
Yield: 63.6 %

Procedure:
A mixture of racemic trans [3-(6-benzenesulfonyl-6H-1,2,3,5,6-pentaaza-as-indacen-1-yl)-cyclopentyl]-carbamic acid tert-butyl ester (2.00 g, 4.14 mmol), aqueous sodium hydroxide solution (10.4 mL, 20.7 mmol, 2M), methanol (30 mL) and THF (50 mL) was stirred at ambient temperature for 45 minutes. DCM was added and the solution washed (water and brine) and concentrated to dryness. Purification by column chromatography on silica gel (gradient: DCM to ethyl acetate) afforded 902 mg (64%) of racemic trans [3-(6H-1,2,3,5,6-pentaaza-as-indacen-1-yl)-cyclopentyl]-carbamic acid tert-butyl ester as an off white solid. LCMS (Method B, ESI): RT=3.21 min, m+H=343.3; 1H NMR (400 MHz, DMSO) δ: 12.34 (s, 1H), 8.99 (s, 1H), 7.60 (d, 1H), 7.18 (d, 1H), 7.03 (d, 1H), 5.64 (m, 1H), 4.23 (m, 1H), 2.47 (m, 2H, partially obscured by DMSO), 2.20 (m, 3H), 1.70 (m, 1H), 1.40 (s, 9H).
Reaction SMILES: C1C=C(Cl)C=C(C(OO)=[O:9])C=1.[Cl:12][C:13]1[CH:18]=[CH:17][N:16]=[CH:15][C:14]=1[F:19]>C(Cl)Cl>[Cl:12][C:13]1[CH:18]=[CH:17][N+:16]([O-:9])=[CH:15][C:14]=1[F:19]
Reactant: Fc1cnccc1Cl
Reactant: O=C(OO)c1cccc(Cl)c1
Solvent: ClCCl
Product: [O-][n+]1ccc(Cl)c(F)c1
Temperature: 25 °C
Reaction time: 60 h

Procedure:
MCPBA (28.1 g) was added to a solution of 4-chloro-3-fluoro-pyridine (10.0 g) in DCM (150 ml) and the reaction mixture stirred for 60 h at RT. The reaction mixture was quenched with 10% aq. Na2S2O3 and the basicity of the aq. phase adjusted with aq. sat. Na2CO3 to pH 9. The aq. phase was extracted with EA (6×), and the combined org. phase was dried over MgSO4 and evaporated to dryness. The desired compound (8.4 g) was used in the next step without further purification.
Reaction SMILES: [C:1](Cl)(=[O:8])[C:2]1[CH:7]=CC=CC=1.[C:10](Cl)(=[O:13])[CH2:11][CH3:12].[C:15]1([CH:21]([OH:32])[CH:22](C)[CH:23]([C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)[OH:24])[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1.C1(C(O)CC(C2C=CC=CC=2)O)C=CC=CC=1>>[C:10]([O:32][CH:21]([C:15]1[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=1)[CH2:22][CH:23]([C:25]1[CH:26]=[CH:27][CH:28]=[CH:29][CH:30]=1)[O:24][C:1](=[O:8])[CH2:2][CH3:7])(=[O:13])[CH2:11][CH3:12]
Reactant: CCC(=O)Cl
Reactant: CC(C(O)c1ccccc1)C(O)c1ccccc1
Reactant: O=C(Cl)c1ccccc1
Agent: OC(CC(O)c1ccccc1)c1ccccc1
Product: CCC(=O)OC(CC(OC(=O)CC)c1ccccc1)c1ccccc1

Procedure:
Synthetic procedure was identical with that described in synthetic example 42(3), except that benzoyl chloride was replaced by propionyl chloride, and 1,3-diphenyl-2-methyl-1,3-propandiol was replaced by 1,3-diphenyl-1,3-propandiol. 1HNMR: δ (ppm) 7.13-7.36(10H, ArH), 5.76(2H, CH), 2.5(4H, CH2), 2.11(2H, CH2), 1.1(6H, CH3)
Reaction SMILES: [C:1]([C:4]1[C:12]2[C:7](=[CH:8][C:9]([O:13][CH3:14])=[CH:10][CH:11]=2)[N:6]([C:15]2[C:24]3[C:19](=[CH:20][CH:21]=[CH:22][CH:23]=3)[N:18]=[CH:17][CH:16]=2)[CH:5]=1)(O)=[O:2].S(Cl)([Cl:27])=O>CN(C)C=O>[Cl:27][C:1]([C:4]1[C:12]2[C:7](=[CH:8][C:9]([O:13][CH3:14])=[CH:10][CH:11]=2)[N:6]([C:15]2[C:24]3[C:19](=[CH:20][CH:21]=[CH:22][CH:23]=3)[N:18]=[CH:17][CH:16]=2)[CH:5]=1)=[O:2]
Reactant: O=S(Cl)Cl
Reactant: COc1ccc2c(C(=O)O)cn(-c3ccnc4ccccc34)c2c1
Solvent: CN(C)C=O
Product: COc1ccc2c(C(=O)Cl)cn(-c3ccnc4ccccc34)c2c1

Procedure:
30 cm3 of sulphinyl chloride and one drop of dimethylformamide are added, at a temperature in the region of 22° C. and under an argon atmosphere, to 2.4 g (7.52 mmol) of 3-carboxy-6-methoxy-1-(quinol-4-yl)-1H-indole. After stirring at reflux for 16 hours, the reaction mixture is concentrated to dryness under reduced pressure (2.7 kPa) to give 2.5 g of 3-chlorocarbonyl-6-methoxy-1-(quinol-4-yl)-1H-indole in the form of a yellow solid which is used directly in the following step.
Reaction SMILES: [C:1]1([N:7]2[C:11]([C:12]3[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=3)=[C:10]([C:18](OCC)=[O:19])[CH:9]=[N:8]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[H-].C([Al+]CC(C)C)C(C)C.Cl>O1CCCC1>[C:1]1([N:7]2[C:11]([C:12]3[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=3)=[C:10]([CH2:18][OH:19])[CH:9]=[N:8]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: CCOC(=O)c1cnn(-c2ccccc2)c1-c1ccccc1
Agent: CC(C)C[Al+]CC(C)C
Agent: Cl
Agent: [H-]
Solvent: C1CCOC1
Product: OCc1cnn(-c2ccccc2)c1-c1ccccc1
Temperature: 25 °C
Reaction time: 1 h
Yield: 98.8 %

Procedure:
To a mixture of ethyl 1,5-diphenyl-1H-pyrazole-4-carboxylate (14.9 g) and tetrahydrofuran (250 ml) was added dropwise diisobutylaluminum hydride (1 mol/l toluene solution, 120 ml) under ice-cooling. The reaction mixture was stirred at room temperature for 1 hr. and poured into a 1N aqueous hydrochloric acid solution. The mixture was extracted with ethyl acetate. The ethyl acetate layer was washed successively with a 1N aqueous hydrochloric acid solution and saturated brine, dried over anhydrous magnesium sulfate, and concentrated to give (1,5-diphenyl-1H-pyrazol-4-yl)methanol (12.6 g, 99%) as colorless crystals. Recrystallization thereof from ethyl acetate-hexane gave colorless prism crystals. melting point: 147-148° C.