Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [N:1]1[C:10]2[C:5](=[CH:6][CH:7]=[C:8]([C:11]([O:13][CH3:14])=[O:12])[CH:9]=2)[CH:4]=[CH:3][CH:2]=1.C(OO)(=[O:17])C>ClCCl.C(=O)(O)[O-].[Na+]>[CH3:14][O:13][C:11]([C:8]1[CH:9]=[C:10]2[C:5]([CH:4]=[CH:3][CH:2]=[N+:1]2[O-:17])=[CH:6][CH:7]=1)=[O:12]
Reactant: COC(=O)c1ccc2cccnc2c1
Reactant: CC(=O)OO
Agent: O=C([O-])O
Agent: [Na+]
Solvent: ClCCl
Product: COC(=O)c1ccc2ccc[n+]([O-])c2c1
Temperature: 25 °C
Reaction time: 8 h
Yield: 90.3 %

Procedure:
To a solution of methyl quinoline-7-carboxylate (17.8 g, 94.87 mmol) in dichloromethane (315 mL) was added peracetic acid (39.9 mL, 190 mmol, 32% in acetic acid). The reaction was stirred at room temperature overnight. Peracetic acid (10 mL, 48 mmol, 32% in acetic acid) was added and the mixture was stirred for 5 h. The reaction mixture was diluted with a saturated solution of aqueous sodium bicarbonate. The aqueous phase was extracted into dichloromethane (2×μL). The extracts were combined, dried over magnesium sulfate, filtered and concentrated under reduced pressure. Purification by flash chromatography (2-15% methanol in dichloromethane) gave the title compound (17.4 g, 90%) as a yellow solid. 1H NMR (400 MHz, CHLOROFORM-d, δ): 9.41 (1H, s), 8.56 (1H, dd, J=6.0, 0.8 Hz), 8.24 (1H, dd, J=8.5, 1.7 Hz), 7.93 (1H, d, J=8.6 Hz), 7.75 (1H, d, J=8.6 Hz), 7.39 (1H, dd, J=8.6, 6.0 Hz), 4.01 (3H, s)
Reaction SMILES: [CH3:1][O:2][C:3]([CH:5]1[CH2:9][CH2:8][C:7](=[O:10])[NH:6]1)=[O:4].[H-].[Na+].Br[CH2:14][C:15]#[N:16]>CC#N>[CH3:1][O:2][C:3]([CH:5]1[CH2:9][CH2:8][C:7](=[O:10])[N:6]1[CH2:14][C:15]#[N:16])=[O:4]
Reactant: COC(=O)C1CCC(=O)N1
Reactant: N#CCBr
Agent: [H-]
Agent: [Na+]
Solvent: CC#N
Product: COC(=O)C1CCC(=O)N1CC#N
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 28.8 %

Procedure:
To a solution of 5-oxo-pyrrolidine-2-carboxylic acid methyl ester (3 g, 21 mmol) in CH3CN (60 ml), 60% NaH (863 mg, 22 mmol) was added at 0° C. After stirring for 30 minutes, a solution of 2-bromoacetonitrile (2.59 g, 21 mmol) in CH3CN (10 ml) was added dropwise. After warming at room temperature, and stirring for 20 hours, the solvent was evaporated under reduced pressure. The residue was partitioned between water and ethyl acetate, the organic layer was washed with brine, dried (Na2SO4) and evaporated. The residue was purified by flash chromatography (from DCM to DCM/MeOH 95/5 respectively) to afford the title compound as a pale yellow oil (1.1 g, 29% yield).
Reaction SMILES: [SH:1][C:2]1[N:11]([CH3:12])[C:10](=[O:13])[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[N:3]=1.[OH-].[Na+].CN(C=O)C.[F:21][C:22]1[CH:37]=[CH:36][C:25]([C:26]([C:28]2[CH:35]=[CH:34][C:31]([CH2:32]Br)=[CH:30][CH:29]=2)=[O:27])=[CH:24][CH:23]=1>C(O)C.O>[F:21][C:22]1[CH:23]=[CH:24][C:25]([C:26]([C:28]2[CH:35]=[CH:34][C:31]([CH2:32][S:1][C:2]3[N:11]([CH3:12])[C:10](=[O:13])[C:9]4[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=4)[N:3]=3)=[CH:30][CH:29]=2)=[O:27])=[CH:36][CH:37]=1
Reactant: O=C(c1ccc(F)cc1)c1ccc(CBr)cc1
Reactant: Cn1c(S)nc2ccccc2c1=O
Agent: [Na+]
Agent: [OH-]
Solvent: CCO
Solvent: O
Solvent: CN(C)C=O
Product: Cn1c(SCc2ccc(C(=O)c3ccc(F)cc3)cc2)nc2ccccc2c1=O
Temperature: 25 °C
Reaction time: 1 h
Yield: 87.9 %

Procedure:
To a solution of 2-mercapto-3-methyl-4(3H)-quinazolinone (1.0 g) and sodium hydroxide (250 mg) in 50% ethanol (15 ml)-DMF (15 ml) was added 4-(4-fluorobenzoyl)benzyl bromide (1.55 g) and the mixture was stirred at room temperature for 1 hour. This reaction mixtrue was poured in water and the resulting crystals were collected by filtration, rinsed with water and methanol, and recrystallized from methanol to provide the title compound as colorless solid (1.85 g). 1H-NMR (CDCl3) δ: 3.61(3H,s), 4.62(2H,s), 7.15(2H,t,J=8.6Hz), 7.40(1H,dt,J=8.2&1.4Hz), 7.58-7.90(8H,m), 8.23(1H,dd,J=8.0&1.4Hz).
Reaction SMILES: [OH:1][CH:2]1[CH:7]([C:8]2[CH:13]=[CH:12][C:11]([CH2:14][OH:15])=[CH:10][CH:9]=2)[CH2:6][CH2:5][N:4]([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH2:3]1.[C:23]1([C:29]([C:37]2[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=2)([C:31]2[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=2)Cl)[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1.C(N(CC)CC)C>C(Cl)Cl>[OH:1][CH:2]1[CH:7]([C:8]2[CH:9]=[CH:10][C:11]([CH2:14][O:15][C:29]([C:23]3[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=3)([C:37]3[CH:38]=[CH:39][CH:40]=[CH:41][CH:42]=3)[C:31]3[CH:32]=[CH:33][CH:34]=[CH:35][CH:36]=3)=[CH:12][CH:13]=2)[CH2:6][CH2:5][N:4]([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH2:3]1
Reactant: CC(C)(C)OC(=O)N1CCC(c2ccc(CO)cc2)C(O)C1
Reactant: ClC(c1ccccc1)(c1ccccc1)c1ccccc1
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: CC(C)(C)OC(=O)N1CCC(c2ccc(COC(c3ccccc3)(c3ccccc3)c3ccccc3)cc2)C(O)C1
Yield: 73.6 %

Procedure:
A solution of 1.50 g (5.14 mmol) of tert-butyl (3RS,4RS)-3-hydroxy-4-(4-hydroxymethyl-phenyl)-piperidine-1-carboxylate, 1.73 g (6.16 mmol) of triphenylchloromethane and 674 mg (6.68 mmol) of triethylamine in 20 ml of methylene chloride was stirred at room temperature for 5 hours. For the working-up, the reaction mixture was washed with 10 ml of water and 10 ml of saturated sodium hydrogen carbonate solution, the organic phase was dried over sodium sulphate and evaporated under reduced pressure. The crude product was chromatographed on silica gel using a 95:5 mixture of toluene and ethyl acetate as the eluent. There were obtained 2.08 g (77.5% of theory) of tert-butyl (3RS,4RS)-3-hydroxy-4-(4-trityloxymethyl-phenyl)-piperidine-1-carboxylate as a colourless foam; MS: 567 (M+NH4)+.
Reaction SMILES: CS(C)=O.C(Cl)(=O)C(Cl)=O.[C:11]([Si:15]([CH3:33])([CH3:32])[O:16][C@H:17]1[CH2:26][CH2:25][CH2:24][C@@:23]2([CH3:27])[C@H:18]1[CH2:19][CH2:20][CH2:21][C@@H:22]2[C@H:28]([CH3:31])[CH2:29][OH:30])([CH3:14])([CH3:13])[CH3:12].CCN(CC)CC>C(Cl)Cl>[C:11]([Si:15]([CH3:33])([CH3:32])[O:16][C@H:17]1[CH2:26][CH2:25][CH2:24][C@@:23]2([CH3:27])[C@H:18]1[CH2:19][CH2:20][CH2:21][C@@H:22]2[C@H:28]([CH3:31])[CH:29]=[O:30])([CH3:13])([CH3:14])[CH3:12]
Reactant: C[C@H](CO)[C@H]1CCC[C@H]2[C@@H](O[Si](C)(C)C(C)(C)C)CCC[C@]12C
Agent: O=C(Cl)C(=O)Cl
Solvent: ClCCl
Solvent: CCN(CC)CC
Solvent: CS(C)=O
Product: C[C@H](C=O)[C@H]1CCC[C@H]2[C@@H](O[Si](C)(C)C(C)(C)C)CCC[C@]12C
Reaction time: 0.5 h
Yield: 88 %

Procedure:
Swern reagent was prepared at -60° C. by adding slowly DMSO (0.899 ml, 11.5 mmol, dissolved in 2 ml of CH2Cl2) to oxalylchloride (0.503 ml, 5.85 mmol) in 10 ml of CH2Cl2. 15 Minutes later, (S)-2-[(1R,4aR,5S,8aR)-5-(tert-Butyl-dimethyl-silanyloxy)-8a-methyl-decahydro-naphthalen-1-yl]-propan-1-ol (1.81 g, 5.31 mmol), dissolved in 7 ml of CH2Cl2, was slowly added. After 1/2 h, NEt3 (5.18 ml, 37.2 mmol) was added and the temperature allowed to reach -25° C. The reaction was quenched by pouring onto crashed ice/NH4Cl, extracted twice with ether, washed with water and brine, dried over sodium sulfate and evaporated to dryness. Flash chromatography (SiO2, hexane/AcOEt=97/3) yielded 1.583 g of (S)-2-[(1R,4aR,5S,8aR)-5-(tert-Butyl-dimethyl-silanyloxy)-8a-methyl-decahydro-naphthalen-1-yl]-propionaldehyde as isomerically pure, colorless oil.
Reaction SMILES: Br[C:2]1[C:11]2[O:10][CH2:9][CH:8]([C:12]3[CH:17]=[CH:16][CH:15]=[CH:14][N:13]=3)[N:7]3[C:18](=[O:20])[NH:19][C:5]([C:6]=23)=[CH:4][CH:3]=1.[C:21]([O:29][CH2:30][C:31]1[O:35][N:34]=[C:33]([CH3:36])[C:32]=1B(O)O)(=[O:28])[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1.ClCCl>O1CCOCC1.O.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[C:21]([O:29][CH2:30][C:31]1[O:35][N:34]=[C:33]([CH3:36])[C:32]=1[C:2]1[C:11]2[O:10][CH2:9][CH:8]([C:12]3[CH:17]=[CH:16][CH:15]=[CH:14][N:13]=3)[N:7]3[C:18](=[O:20])[NH:19][C:5]([C:6]=23)=[CH:4][CH:3]=1)(=[O:28])[C:22]1[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=1
Reactant: O=c1[nH]c2ccc(Br)c3c2n1C(c1ccccn1)CO3
Reactant: Cc1noc(COC(=O)c2ccccc2)c1B(O)O
Agent: Cl[Pd]Cl
Agent: [Fe+2]
Agent: c1ccc(P(c2ccccc2)[c-]2cccc2)cc1
Solvent: O
Solvent: C1COCCO1
Solvent: ClCCl
Product: Cc1noc(COC(=O)c2ccccc2)c1-c1ccc2[nH]c(=O)n3c2c1OCC3c1ccccn1
Temperature: 80 °C
Yield: 60.7 %

Procedure:
A solution of 7-bromo-4-pyridin-2-yl-4,5-dihydroimidazo[1,5,4-de][1,4]benzoxazin-2(1H)-one (687 mg, 2.07 mmol) and {5-[(benzoyloxy)methyl]-3-methylisoxazol-4-yl}boronic acid (1.08 g, 4.14 mmol) in 1,4-dioxane (15.7 mL) and water (4 mL) was degassed with nitrogen. The reaction mixture was treated with [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II), complex with dichloromethane (1:1) (253 mg, 0.310 mmol), degassed with nitrogen, and heated in a sealed tube at 80° C. for 30 min, at which time the reaction mixture was treated with {5-[(benzoyloxy)methyl]-3-methylisoxazol-4-yl}boronic acid (1.08 g, 4.14 mmol) and [1,1′-bis(diphenylphosphino)ferrocene]-dichloropalladium(II), complex with dichloromethane (1:1) (10 mg, 12.2 mol), degassed with nitrogen and heated at 80° C. for a further 30 min. The reaction mixture was then diluted with ethyl acetate and water. The organic layer was separated and washed with brine, dried over magnesium sulfate, filtered, and concentrated to give the crude product. Purification by flash column chromatography (30% ethyl acetate/hexanes to 100% ethyl acetate [the ethyl acetate contained 5% methanol]) gave the desired product (0.589 g, 58%) as a racemic mixture. LCMS calculated for C26H21N4O5 (M+H)+: m/z=469.1. found: 469.1.
Reaction SMILES: [F:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]([OH:8])=O)=[CH:4][CH:3]=1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CN1CCOCC1.[CH3:42][O:43][C:44]1[C:45]2[N:58]=[C:57]([NH2:59])[S:56][C:46]=2[C:47]([N:50]2[CH2:55][CH2:54][O:53][CH2:52][CH2:51]2)=[N:48][CH:49]=1>C1COCC1>[F:1][C:2]1[CH:3]=[CH:4][C:5]([C:6]([NH:59][C:57]2[S:56][C:46]3[C:47]([N:50]4[CH2:55][CH2:54][O:53][CH2:52][CH2:51]4)=[N:48][CH:49]=[C:44]([O:43][CH3:42])[C:45]=3[N:58]=2)=[O:8])=[CH:9][CH:10]=1
Reactant: COc1cnc(N2CCOCC2)c2sc(N)nc12
Reactant: O=C(O)c1ccc(F)cc1
Agent: CN(C)C(On1nnc2cccnc21)=[N+](C)C
Agent: F[P-](F)(F)(F)(F)F
Solvent: CN1CCOCC1
Solvent: C1CCOC1
Product: COc1cnc(N2CCOCC2)c2sc(NC(=O)c3ccc(F)cc3)nc12
Reaction time: 8 h
Yield: 57 %

Procedure:
To a stirred solution of 79 mg (0.56 mmol) 4-fluoro-benzoic acid in 4 ml THF were added 225 mg (0.59 mmol) HATU and 0.12 ml (1.13 mmol) N-methylmorpholine and stirring continued at 30° C. for 8 h. 75 mg (0.28 mmol) 7-methoxy-4-morpholin-4-yl-thiazolo[5,4-c]pyridin-2-ylamine was then added and stirring continued at 35° C. for 48 h. The reaction mixture was then partitioned between tetrahydrofuran and saturated brine. The organic phases was dried over sodium sulfate and concentrated in vacuo. Flash chromatography (ethyl acetate/heptane) followed by trituration in ether afforded 62 mg (56%) 4-fluoro-N-(7-methoxy-4-morpholin-4-yl-thiazolo[5,4-c]pyridin-2-yl)-benzamide as a white crystalline solid. ES-MS m/e (%): 389 (M+H+, 100).
Reaction SMILES: [CH:1]1([N:6]2[C:10]3=[N:11][C:12](S(C)(=O)=O)=[N:13][C:14](=[O:15])[C:9]3=[C:8]([CH2:20][CH3:21])[NH:7]2)[CH2:5][CH2:4][CH2:3][CH2:2]1.[C:22]1([OH:28])[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1.[H-].[Na+]>O>[CH:1]1([N:6]2[C:10]3=[N:11][C:12]([O:28][C:22]4[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=4)=[N:13][C:14](=[O:15])[C:9]3=[C:8]([CH2:20][CH3:21])[NH:7]2)[CH2:5][CH2:4][CH2:3][CH2:2]1
Reactant: CCc1[nH]n(C2CCCC2)c2nc(S(C)(=O)=O)nc(=O)c1-2
Reactant: Oc1ccccc1
Agent: [H-]
Agent: [Na+]
Solvent: O
Product: CCc1[nH]n(C2CCCC2)c2nc(Oc3ccccc3)nc(=O)c1-2
Yield: 67.4 %

Procedure:
A mixture of 1-cyclopentyl-3-ethyl-6-(methylsulfonyl)pyrazolo[3,4-d]pyrimidin-4-one (3 g, 9.6 mmol), phenol (6 g, 64 mmol) and NaH (0.5 g, 12.8 mmol, 60% dispersion in mineral oil) was heated at 170°-175° C. for 5 hours. The reaction mixture was poured into water (50 mL) and extracted with CHCl3 (100 mL). The CHCl3 layer was concentrated in vacuo and the residue was purified by column chromatography on silica gel eluting with 10% ether/hexane to afford 2.1 g (68%) of 1-cyclopentyl-3-ethyl-6-(phenyloxy)pyrazolo[3,4-d]pyrimidin-4-one, as a white solid, m.p. 175°-177° C.
Reaction SMILES: [CH3:1][O:2][C:3](=[O:20])[CH2:4][C:5]1[CH:10]=[CH:9][CH:8]=[C:7]([NH:11][C:12]([C:14]2[O:15][C:16](Br)=[CH:17][CH:18]=2)=[O:13])[CH:6]=1.[Cl:21][C:22]1[CH:27]=[C:26]([Cl:28])[CH:25]=[CH:24][C:23]=1B(O)O>>[CH3:1][O:2][C:3](=[O:20])[CH2:4][C:5]1[CH:10]=[CH:9][CH:8]=[C:7]([NH:11][C:12]([C:14]2[O:15][C:16]([C:25]3[CH:24]=[CH:23][C:22]([Cl:21])=[CH:27][C:26]=3[Cl:28])=[CH:17][CH:18]=2)=[O:13])[CH:6]=1
Reactant: OB(O)c1ccc(Cl)cc1Cl
Reactant: COC(=O)Cc1cccc(NC(=O)c2ccc(Br)o2)c1
Product: COC(=O)Cc1cccc(NC(=O)c2ccc(-c3ccc(Cl)cc3Cl)o2)c1

Procedure:
Methyl ester (16) (100 mg, 0.30 mmol) was coupled to 2,4-dichloro-phenylboronic acid (61 mg, 0.33 mmol) using Method E. The crude compound was purified by column chromatography, eluting in 17% EtOAc in heptane to give the title compound. Yield: 37 mg, 31%; LC/MS tr 1.76 min; MS(ES+) m/z 404, 406 (M+H)
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]=[C:7]([C:12]1[CH:17]=[CH:16][C:15]([F:18])=[CH:14][CH:13]=1)[N:6]=[C:5]2[C:19](O)=[O:20].Cl.[CH3:23][O:24][C:25]1[CH:26]=[C:27]2[C:32](=[CH:33][CH:34]=1)[CH2:31][NH:30][CH2:29][CH2:28]2>>[F:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]=[C:7]([C:12]1[CH:13]=[CH:14][C:15]([F:18])=[CH:16][CH:17]=1)[N:6]=[C:5]2[C:19]([N:30]1[CH2:29][CH2:28][C:27]2[C:32](=[CH:33][CH:34]=[C:25]([O:24][CH3:23])[CH:26]=2)[CH2:31]1)=[O:20]
Reactant: O=C(O)c1nc(-c2ccc(F)cc2)nc2ccc(F)cc12
Reactant: COc1ccc2c(c1)CCNC2
Agent: Cl
Product: COc1ccc2c(c1)CCN(C(=O)c1nc(-c3ccc(F)cc3)nc3ccc(F)cc13)C2
Yield: 50.6 %

Procedure:
Reaction of 6-fluoro-2-(4-fluorophenyl)quinazoline-4-carboxylic acid with 6-methoxy-1,2,3,4-tetrahydroisoquinoline hydrochloride gave compound 99 (50.6% yield). 1H NMR (400 MHz, DMSO-d6) δ 2.80 and 3.03 (2t, 2H), 3.54 and 4.02 (2t, 2H), 3.72 and 3.74 (2s, 3H), 4.47 and 4.92 (2s, 2H), 6.65-7.27 (m, 3H), 7.40-7.48 (m, 1H), 7.62-7.82 (m, 2H), 8.05-8.10 (m, 1H), 8.20-8.39 (m, 3H); MS (ESI) m/z 432 ([M+H]+).
Reaction SMILES: [CH2:1]([C:3](=[CH:6][CH2:7][C:8]1[C:9]([O:21][CH2:22][CH2:23][Si:24]([CH3:27])([CH3:26])[CH3:25])=[C:10]2[C:14](=[C:15]([CH3:19])[C:16]=1[O:17][CH3:18])[CH2:13][O:12][C:11]2=[O:20])[CH:4]=[O:5])[CH3:2].[Li+].[BH4-]>CO.C1COCC1>[OH:5][CH2:4][C:3]([CH2:1][CH3:2])=[CH:6][CH2:7][C:8]1[C:9]([O:21][CH2:22][CH2:23][Si:24]([CH3:25])([CH3:27])[CH3:26])=[C:10]2[C:14]([CH2:13][O:12][C:11]2=[O:20])=[C:15]([CH3:19])[C:16]=1[O:17][CH3:18]
Reactant: CCC(C=O)=CCc1c(OC)c(C)c2c(c1OCC[Si](C)(C)C)C(=O)OC2
Agent: [BH4-]
Agent: [Li+]
Solvent: C1CCOC1
Solvent: CO
Product: CCC(=CCc1c(OC)c(C)c2c(c1OCC[Si](C)(C)C)C(=O)OC2)CO
Temperature: 25 °C
Reaction time: 0.67 h
Yield: 73.2 %

Procedure:
A solution of 2-ethyl-4-[6-methoxy-7-methyl-3-oxo-4-(2-trimethylsilanyl-ethoxy)-1,3-dihydro-isobenzofuran-5-yl]-but-2-enal (1.3 g, 3.30 mmol) in methanol (10 mL) and THF (10 mL) was cooled to 0° C. A solution of CeCl3 (8.25 mL, 0.4M, MeOH: H2O, 9:1) was added, followed by LiBH4 (1.66 mL, 3.30 mmol of a 2M solution in THF). The ice bath was removed and the reaction mixture was allowed to warm to room temperature. The reaction mixture was stirred for an additional 40 minutes whereupon TLC indicated complete consumption of starting aldehyde. The reaction was worked up by addition of aqueous 1N HCl and the product was extracted with EtOAc. The organic layer was washed with saturated aqueous sodium bicarbonate solution and brine. The organic layer was concentrated under reduced pressure and the residue was purified by silica gel chromatography to provide 948 mg (73%) of the product as colorless oil. 1H NMR (300 MHz, CDCl3) δ 0.00 (s, 9H), 1.07 (t, 3H), 1.20 (dd, 2H, J=7, 8 Hz), 2.13 (s, 3H), 2.38-2.50 (m, 2H), 3.77 (s, 3H), 3.99 (s, 2H), 4.27 (dd, 2H, J=7, 8 Hz), 5.08 (s, 2H), 5.34 (t, J=7.2 Hz, 1H) ppm.
Reaction SMILES: C1(C2[C:5](=CC=CC=2)[CH:4]([O:11][C:12](=[O:35])[CH2:13][CH2:14][CH2:15][CH2:16][CH:17]2[S:34][C@H:20]3[CH2:21][C@@H:22]([OH:33])[C@H:23](/[CH:24]=[CH:25]/[C@@H:26]([OH:32])[CH2:27][CH2:28][CH2:29][CH2:30][CH3:31])[C@H:19]3[CH2:18]2)O1)=O.[OH:36]C1C2C(=CC=CC=2)C(=O)O1>>[OH:36][CH2:5][CH2:4][O:11][C:12](=[O:35])[CH2:13][CH2:14][CH2:15][CH2:16][CH:17]1[S:34][C@H:20]2[CH2:21][C@@H:22]([OH:33])[C@H:23](/[CH:24]=[CH:25]/[C@@H:26]([OH:32])[CH2:27][CH2:28][CH2:29][CH2:30][CH3:31])[C@H:19]2[CH2:18]1
Reactant: CCCCC[C@H](O)/C=C/[C@@H]1[C@H]2CC(CCCCC(=O)OC3OC(=O)c4ccccc43)S[C@H]2C[C@H]1O
Reactant: O=C1OC(O)c2ccccc21
Product: CCCCC[C@H](O)/C=C/[C@@H]1[C@H]2CC(CCCCC(=O)OCCO)S[C@H]2C[C@H]1O

Procedure:
(13E)-(6RS,9α,11α,15S)-6,9-Epithio-11,15-dihydroxyprost-13-enoic acid phthalid-3-yl ester from 3-hydroxyphthalide.
Reaction SMILES: [NH2:1][C:2]1[CH:9]=[CH:8][CH:7]=[C:6](F)[C:3]=1[C:4]#[N:5].[CH3:11][O-:12].[Na+]>CN(C)C=O.CO.C(OCC)(=O)C>[NH2:1][C:2]1[CH:9]=[CH:8][CH:7]=[C:6]([O:12][CH3:11])[C:3]=1[C:4]#[N:5]
Reactant: N#Cc1c(N)cccc1F
Reactant: C[O-]
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: CCOC(C)=O
Solvent: CO
Product: COc1cccc(N)c1C#N

Procedure:
A solution of 70 g (0.5 mol) of 2-amino-6-fluorobenzonitrile (prepared, e.g. according to U.S. Pat. No. 4,504,660) in 250 ml of N,N-dimethylformamide was prepared, and a solution of 30.6 g (0.55 mol) of sodium methoxide in 70 ml of methanol was added dropwise at room temperature while stirring. The mixture was then refluxed for 5 hours with stirring. The completion of the reaction was monitored by TLC. An additional 25 g of sodium methoxide in 35 ml methanol were added and the reaction mixture was refluxed for an additional 4 hours while stirring. The reaction mixture was concentrated under reduced pressure. The resulting residue was triturated with water, filtered off with suction and the solids obtained were dissolved in ethyl acetate. The resulting solution was concentrated in vacuo. The obtained residue was triturated with petroleum ether and filtered off with suction. Yield: 48 g (63% of theory) of a brownish solid having a melting point of 143-146° C.
Reaction SMILES: [CH2:1]([Br:10])[C:2]([C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1)=[O:3].C[Si](C)(C)[N:13]1[CH:17]=[N:16][C:15]([S:18][Si](C)(C)C)=[N:14]1.CO>C(#N)C.CN(C)P(=O)(N(C)C)N(C)C>[BrH:10].[CH2:1]([S:18][C:15]1[N:16]=[CH:17][NH:13][N:14]=1)[C:2]([C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1)=[O:3]
Reactant: O=C(CBr)c1ccccc1
Reactant: C[Si](C)(C)Sc1ncn([Si](C)(C)C)n1
Solvent: CN(C)P(=O)(N(C)C)N(C)C
Solvent: CC#N
Solvent: CO
Product: Br
Product: O=C(CSc1nc[nH]n1)c1ccccc1
Temperature: 25 °C
Reaction time: 0.25 h
Yield: 79.4 %

Procedure:
1.62 g (8.1 mmoles) of phenacyl bromide were added to a solution of 1.90 g (7.76 mmoles) of 1-trimethylsilyl-3-trimethylsilylthio-1H-1,2,4-triazole in 10 ml of acetonitrile and 1.55 ml of hexamethylphosphoric triamide and the reaction was complete after stirring for 15 minutes at room temperature. The precipitate formed after the addition of 4 ml of methanol was filtered off and was washed with diethyl ether and with hexane to obtain a yield of 1.85 g (79.5%) of 3-phenacylthio-1H-1,2,4-triazole hydrobromide melting at 201.5°-202° C. (dec.). A second crop of 0.3 g (13%) melting at 191°-192° C. (dec.)) was isolated from the mother liquor. 0.90 g of this salt was taken up in 10 ml of water which was layered with 20 ml of ethyl acetate. The pH was adjusted to 9 with 1N potassium hydroxide and the free base was extracted from the water layer with ethylacetate to obtain 0.66 g (100% yield) of 3-phenacylthio-1H-1,2,4-triazole melting at 119°-120° C. Crystallization from ethyl acetate raised the melting point to 120°-121° C.
Reaction SMILES: [N:1]1[CH:6]=[CH:5][C:4]([CH2:7][C:8]2([CH2:23][C:24]3[CH:29]=[CH:28][N:27]=[CH:26][CH:25]=3)[C:16]3[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=3)[C:10]([C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=3)=[CH:9]2)=[CH:3][CH:2]=1.S(=O)(O)[O-:31].[Na+].[OH2:35]>N1C=CC=CC=1.[Os](=O)(=O)(=O)=O>[N:1]1[CH:2]=[CH:3][C:4]([CH2:7][C:8]2([CH2:23][C:24]3[CH:25]=[CH:26][N:27]=[CH:28][CH:29]=3)[C:16]3[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=3)[C:10]([C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=3)([OH:35])[CH:9]2[OH:31])=[CH:5][CH:6]=1
Reactant: C1=C(c2ccccc2)c2ccccc2C1(Cc1ccncc1)Cc1ccncc1
Reactant: O
Reactant: O=S([O-])O
Agent: O=[Os](=O)(=O)=O
Agent: [Na+]
Solvent: c1ccncc1
Product: OC1C(Cc2ccncc2)(Cc2ccncc2)c2ccccc2C1(O)c1ccccc1
Temperature: 25 °C

Procedure:
To a solution of 1,1-Bis(4-pyridinylmethyl)-3-phenyl-1H-indene (1.0 g, 2.7 mmol) in dry pyridine (10 ml) was added osmium tetroxide (1.0 g, 3.9 mmol, dissolved in ether). The mixture was stirred at room temperature and monitored by TLC. After completion of the reaction, sodium bisulfite (2.0 g), water (20 ml), and pyridine (5 ml) was added. The mixture was stirred for 1 h, and extracted three times with chloroform: isopropanol (4:1). The combined extracts were washed with brine, dried over magnesium sulfate, and evaporated to give 3,3-bis(4-pyridinylmethyl)-2,3-dihydro-1-phenyl-1H-indene-1,2-diol as a yellow solid, 1.15 g.
Reaction SMILES: CCCCCC.C([Li])CCC.Br[C:13]1[CH:14]=[C:15]([F:19])[CH:16]=[CH:17][CH:18]=1.[C:20]1([C:26]2[C:31]([C:32]3[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=3)=[N:30][CH:29]=[CH:28][N:27]=2)[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1>O.O1CCCC1>[F:19][C:15]1[CH:14]=[C:13]([C:29]2[N:30]=[C:31]([C:32]3[CH:33]=[CH:34][CH:35]=[CH:36][CH:37]=3)[C:26]([C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=3)=[N:27][CH:28]=2)[CH:18]=[CH:17][CH:16]=1
Reactant: c1ccc(-c2nccnc2-c2ccccc2)cc1
Reactant: Fc1cccc(Br)c1
Agent: [Li]CCCC
Solvent: O
Solvent: CCCCCC
Solvent: C1CCOC1
Product: Fc1cccc(-c2cnc(-c3ccccc3)c(-c3ccccc3)n2)c1
Reaction time: 0.5 h
Yield: 8 %

Procedure:
First, 7.5 mL (1.58 mol/L) of hexane solution of n-butyllithium was added dropwise to a mixed solution of 1.49 g of 3-bromofluorobenzene and 11 mL of tetrahydrofuran at −78° C. under an atmosphere of nitrogen, and stirred for 30 minutes, keeping the temperature at −78° C. The obtained solution was added dropwise to a mixed solution, which was cooled with ice, of 2.45 g of 2,3-diphenylpyrazine and 20 mL of tetrahydrofuran, and stirred for 1 hour at room temperature. Water was added to this mixture and an organic layer was extracted using ethyl acetate as an extraction solvent. The obtained organic layer was washed with water and dried with anhydrous magnesium sulfate. After drying, the solution was filtrated. The solvent of the solution was distilled off and the residue obtained by distillation was purified by silica gel column chromatography using dichloromethane as a developing solvent. In this way, Hdppr-3FP (an orange powder, yield: 8%), which was a target substance was obtained. A synthetic scheme of Step 1 is shown by a following (c-2).
Reaction SMILES: [CH:1]1([C:4]2[N:9]3[N:10]=[CH:11][C:12]([C:13]#[CH:14])=[C:8]3[N:7]=[C:6]([C:15]3[CH:20]=[CH:19][C:18]([Cl:21])=[C:17]([Cl:22])[CH:16]=3)[CH:5]=2)[CH2:3][CH2:2]1.Br[C:24]1[CH:29]=[CH:28][C:27]([S:30]([NH2:33])(=[O:32])=[O:31])=[CH:26][CH:25]=1>>[CH:1]1([C:4]2[N:9]3[N:10]=[CH:11][C:12]([C:13]#[C:14][C:25]4[CH:26]=[C:27]([S:30]([NH2:33])(=[O:32])=[O:31])[CH:28]=[CH:29][CH:24]=4)=[C:8]3[N:7]=[C:6]([C:15]3[CH:20]=[CH:19][C:18]([Cl:21])=[C:17]([Cl:22])[CH:16]=3)[CH:5]=2)[CH2:3][CH2:2]1
Reactant: C#Cc1cnn2c(C3CC3)cc(-c3ccc(Cl)c(Cl)c3)nc12
Reactant: NS(=O)(=O)c1ccc(Br)cc1
Product: NS(=O)(=O)c1cccc(C#Cc2cnn3c(C4CC4)cc(-c4ccc(Cl)c(Cl)c4)nc23)c1

Procedure:
The title compound was prepared from 7-cyclopropyl-5-(3,4-dichloro-phenyl)-3-ethynyl-pyrazolo[1,5-a]pyrimidine (example C.8) (82 mg, 0.25 mmol) and 4-bromo-benzenesulfonamide (59 mg, 0.25 mmol) according to general procedure II. Obtained as a yellow solid (37 mg, 30%). MS (ISP) 483.5 [(M+H)+]; mp 200-202° C.