Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [C:1](Cl)(Cl)=[S:2].[Cl:5][C:6]1[CH:12]=[C:11]([O:13][CH3:14])[CH:10]=[C:9]([Cl:15])[C:7]=1[NH2:8]>O1CCCC1.C(=O)([O-])O.[Na+]>[Cl:5][C:6]1[CH:12]=[C:11]([O:13][CH3:14])[CH:10]=[C:9]([Cl:15])[C:7]=1[N:8]=[C:1]=[S:2]
Reactant: S=C(Cl)Cl
Reactant: COc1cc(Cl)c(N)c(Cl)c1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: C1CCOC1
Product: COc1cc(Cl)c(N=C=S)c(Cl)c1
Temperature: 25 °C
Reaction time: 1 h
Yield: 90.8 %

Procedure:
Thiophosgene (1.62 mL, 21.8 mmol) was added dropwise to a stirred mixture of 2,6-dichloro-4-methoxyaniline (2.00 g, 10.4 mmol) in tetrahydrofuran (25 mL) and saturated aqueous sodium hydrogen carbonate (25 mL) at 0° C. The mixture was stirred at room temperature for 1 h, and extracted with ethyl acetate. The combined organic layer was washed with brine, dried over anhydrous sodium sulfate, filtered and concentrated in vacuo. The residue was washed with n-hexane to give the title compound as a brown solid (2.21 g, 9.44 mmol, 91%).
Reaction SMILES: [C:1]([NH:9][C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=1[N:16]1[C:24]2[C:19](=[CH:20][C:21]([Cl:25])=[CH:22][CH:23]=2)[CH2:18][CH2:17]1)(=O)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.O=P(Cl)(Cl)Cl>C(Cl)Cl>[ClH:25].[Cl:25][C:21]1[CH:20]=[C:19]2[C:24]3=[C:23]([CH:22]=1)[C:1]([C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1)=[N:9][C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=1[N:16]3[CH2:17][CH2:18]2
Reactant: O=C(Nc1ccccc1N1CCc2cc(Cl)ccc21)c1ccccc1
Solvent: ClCCl
Solvent: O=P(Cl)(Cl)Cl
Product: Cl
Product: Clc1cc2c3c(c1)C(c1ccccc1)=Nc1ccccc1N3CC2
Temperature: 25 °C
Reaction time: 8 h

Procedure:
An ice cold solution of 43.48 g of 1-(2-benzamidophenyl)-5-chloroindoline in 150 ml CH2Cl2 is treated dropwise over 80 minutes with 215 ml POCl3. At the end of the addition, the reaction mixture is permitted to warm to room temperature and the solvent (CH2Cl2) is distilled off at ambient pressure. The resulting POCl3 solution is heated at reflux for 5 hours and then permitted to cool under N2 to room temperature and stand overnight. The POCl3 is distilled off at aspirator pressure. The resulting crude salt is treated cautiously with absolute ethanol and then boiled. The product is filtered, washed with 1:1 ethanol-ether, then with dry ether and is suction dried. Recrystallization from hot ethanol affords 4-chloro-1,2-dihydro-6-phenylindolo[1,7-ab][1,5]benzodiazepine hydrochloride, m.p. 231° C. dec.
Reaction SMILES: [CH3:1][C:2]([N:11]1[CH:15]=[C:14]([NH:16][C:17](=[O:23])[CH:18]([NH2:22])[CH2:19][CH2:20][CH3:21])[N:13]=[CH:12]1)([CH3:10])[CH2:3][N:4]1[CH2:9][CH2:8][O:7][CH2:6][CH2:5]1.[Cl:24][C:25]1[CH:26]=[C:27]2[C:32](=[C:33]([Cl:35])[CH:34]=1)[CH2:31][C:30](=O)[CH2:29][CH2:28]2>>[CH3:1][C:2]([N:11]1[CH:15]=[C:14]([NH:16][C:17](=[O:23])[CH:18]([NH:22][CH:30]2[CH2:29][CH2:28][C:27]3[C:32](=[C:33]([Cl:35])[CH:34]=[C:25]([Cl:24])[CH:26]=3)[CH2:31]2)[CH2:19][CH2:20][CH3:21])[N:13]=[CH:12]1)([CH3:10])[CH2:3][N:4]1[CH2:5][CH2:6][O:7][CH2:8][CH2:9]1
Reactant: CCCC(N)C(=O)Nc1cn(C(C)(C)CN2CCOCC2)cn1
Reactant: O=C1CCc2cc(Cl)cc(Cl)c2C1
Product: CCCC(NC1CCc2cc(Cl)cc(Cl)c2C1)C(=O)Nc1cn(C(C)(C)CN2CCOCC2)cn1

Procedure:
2-Amino-pentanoic acid [1-(1,1-dimethyl-2-morpholin-4-yl-ethyl)-1H-imidazol-4-yl]-amide was reacted with 6,8-Dichloro-3,4-dihydro-1H-naphthalen-2-one to provide the title compound: C13 NMR (100 MHz, CDCl3) 14.2, 19.5, 25.9, 26.0, 28.5, 29.4, 34.0, 34.6, 36.5, 52.7, 53.4, 55.5, 58.9, 60.9, 67.5, 68.9, 104.6, 126.7, 127.2, 127.3, 131.2, 131.4, 131.8, 137.4, 139.9.
Reaction SMILES: [CH2:1]([O:3][C:4](=[O:18])[C:5]([O:8][C:9]1[CH:14]=[CH:13][C:12]([CH2:15][NH2:16])=[CH:11][C:10]=1[CH3:17])([CH3:7])[CH3:6])[CH3:2].[CH:19]1([C:22]2[C:27]([C:28](O)=[O:29])=[CH:26][N:25]=[C:24]([C:31]3[CH:36]=[CH:35][C:34]([C:37]([F:40])([F:39])[F:38])=[CH:33][CH:32]=3)[N:23]=2)[CH2:21][CH2:20]1>>[CH2:1]([O:3][C:4](=[O:18])[C:5]([O:8][C:9]1[CH:14]=[CH:13][C:12]([CH2:15][NH:16][C:28]([C:27]2[C:22]([CH:19]3[CH2:21][CH2:20]3)=[N:23][C:24]([C:31]3[CH:32]=[CH:33][C:34]([C:37]([F:39])([F:40])[F:38])=[CH:35][CH:36]=3)=[N:25][CH:26]=2)=[O:29])=[CH:11][C:10]=1[CH3:17])([CH3:6])[CH3:7])[CH3:2]
Reactant: O=C(O)c1cnc(-c2ccc(C(F)(F)F)cc2)nc1C1CC1
Reactant: CCOC(=O)C(C)(C)Oc1ccc(CN)cc1C
Product: CCOC(=O)C(C)(C)Oc1ccc(CNC(=O)c2cnc(-c3ccc(C(F)(F)F)cc3)nc2C2CC2)cc1C

Procedure:
In analogy to the procedures described in example 26B] and 26C], 2-(4-aminomethyl-2-methyl-phenoxy)-2-methyl-propionic acid ethyl ester (example 97B]) was reacted with 4-cyclopropyl-2-(4-trifluoromethyl-phenyl)-pyrimidine-5-carboxylic acid (example 53B]) to give 2-[4-({[4-cyclopropyl-2-(4-trifluoromethyl-phenyl)-pyrimidine-5-carbonyl]-amino}-methyl)-2-methyl-phenoxy]-2-methyl-propionic acid ethyl ester, which was subsequently saponified to yield the title compound as light yellow foam.
Reaction SMILES: Br[CH2:2][CH2:3][Cl:4].C(=O)([O-])[O-].[K+].[K+].[C:11]([N:14]1[C:18]2[CH:19]=[CH:20][CH:21]=[CH:22][C:17]=2[NH:16][C:15]1=[O:23])([CH3:13])=[CH2:12]>CN(C)C=O>[Cl:4][CH2:3][CH2:2][N:16]1[C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=2[N:14]([C:11]([CH3:13])=[CH2:12])[C:15]1=[O:23]
Reactant: C=C(C)n1c(=O)[nH]c2ccccc21
Reactant: ClCCBr
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: C=C(C)n1c(=O)n(CCCl)c2ccccc21
Reaction time: 48 h

Procedure:
200 mmol of 1-bromo-2-chloroethane and 55 mmol of potassium carbonate are added to 50 mmol of 1-isopropenyl-2(3H)-benzimidazolone in 150 ml of dimethylformamide. The whole mixture is kept stirring for 48 hours. It is then poured into ice-cold water and extracted with dichloromethane. The organic phases are washed with water, dried and evaporated. The residue is then taken up in ether. The ether phase is washed with 2N potassium hydroxide and then with water, dried and evaporated and leads to the expected product.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([C:12]2[N:16]=[C:15]([C:17]3[CH:24]=[CH:23][C:20]([CH:21]=O)=[CH:19][CH:18]=3)[O:14][N:13]=2)[CH:5]=[CH:6][C:7]=1[O:8][CH:9]([CH3:11])[CH3:10].[CH3:25][C:26]1([CH3:33])[O:30][CH:29]([CH2:31][NH2:32])[CH2:28][O:27]1.C(O)(=O)C.C([BH3-])#N.[Na+]>CO>[Cl:1][C:2]1[CH:3]=[C:4]([C:12]2[N:16]=[C:15]([C:17]3[CH:18]=[CH:19][C:20]([CH2:21][NH:32][CH2:31][CH:29]4[CH2:28][O:27][C:26]([CH3:33])([CH3:25])[O:30]4)=[CH:23][CH:24]=3)[O:14][N:13]=2)[CH:5]=[CH:6][C:7]=1[O:8][CH:9]([CH3:10])[CH3:11]
Reactant: CC(C)Oc1ccc(-c2noc(-c3ccc(C=O)cc3)n2)cc1Cl
Reactant: CC1(C)OCC(CN)O1
Agent: [BH3-]C#N
Agent: [Na+]
Solvent: CC(=O)O
Solvent: CO
Product: CC(C)Oc1ccc(-c2noc(-c3ccc(CNCC4COC(C)(C)O4)cc3)n2)cc1Cl
Temperature: 25 °C
Reaction time: 0.17 h
Yield: 65.3 %

Procedure:
4-(3-(3-chloro-4-isopropoxyphenyl)-1,2,4-oxadiazol-5-yl)benzaldehyde (150 mg, 0.438 mmol), (2,2-dimethyl-1,3-dioxolan-4-yl)methanamine (0.057 mL, 0.438 mmol), methanol (4 mL), and acetic acid (0.125 mL, 2.188 mmol) were loaded into a 25 mL flask equipped with a stirring bar. The mixture was stirred for about 10 minutes at room temperature under nitrogen. Sodium cyanoborohydride (27.5 mg, 0.438 mmol) was added in one portion, and the reaction mixture was stirred at room temperature overnight. Solvent was removed under reduced pressure and crude material was purified by RP-HPLC (A=50 mM ammonium acetate, B=ACN; 40% to 80% B over 30 min at 21.0 mL/min; UV λ=254 nm; Thermo Hyperprep HS C18, 8 μm, 250×21.2 mm column). Fractions containing product were combined, rotovapped and lyophilized to give N-(4-(3-(3-chloro-4-isopropoxyphenyl)-1,2,4-oxadiazol-5-yl)benzyl)-1-(2,2-dimethyl-1,3-dioxolan-4-yl)methanamine (130.9 mg, 64.7%) as a white solid. LCMS (Table 1, Method c) Rt=2.59 min, m/z 458.62 (M+H)+; 1H NMR (400 MHz, DMSO) δ ppm 8.13 (d, 2H), 8.06 (d, 1H), 8.00 (dd, 1H), 7.61 (d, 2H), 7.39 (d, 1H), 4.82 (sept, 1H), 4.15 (p, 1H), 3.99 (dd, 1H), 3.84 (s, 2H), 3.63 (dd, 1H), 2.61 (ddd, 2H), 1.86 (s, 4H), 1.35 (d, 6H) 1.26 (s, 3H).
Reaction SMILES: [CH2:1]=[CH:2][C:3](=[CH2:5])[CH3:4].[C:6]([OH:9])(=[O:8])[CH3:7].[Cl:10]OC(C)(C)C>O>[C:6]([O:9][C:3]([CH3:4])([CH:2]=[CH2:1])[CH2:5][Cl:10])(=[O:8])[CH3:7]
Reactant: CC(C)(C)OCl
Reactant: CC(=O)O
Reactant: C=CC(=C)C
Solvent: O
Product: C=CC(C)(CCl)OC(C)=O
Yield: 73.8 %

Procedure:
82 g (1.2 mol) of Isoprene and 360 g of glacial acetic acid were mixed. With stirring under ice cooling and with keeping an internal temperature at 10°-15° C., 108 g (1.0 mol) of t-butyl hypochlorite were added dropwise therein. The resulting mixture was continuously stirred as it was until the yellow color of said t-butyl hypochlorite disapperared from the reaction liquid. After water (500 ml) was added into the reaction liquid, it was extracted with ether (300 ml×2). After the organic layer was washed with an aqueous solution saturated with sodium hydrogencarbonate, and thereafter with water and dried, it was concentrated under reduced pressure, thereby obtaining an oily residue. This residue was distilled under reduced pressure, whereby 120 g of the title compound were obtained. (Yield: 43%)
Reaction SMILES: [CH3:1][C:2]1[CH:8]=[C:7](C)[C:5]([NH2:6])=[C:4]([N+:10]([O-])=O)[CH:3]=1.[CH2:13](O)C>[Pd]>[NH2:6][C:5]1[CH:7]=[C:8]([CH3:13])[C:2]([CH3:1])=[CH:3][C:4]=1[NH2:10]
Reactant: Cc1cc(C)c(N)c([N+](=O)[O-])c1
Reactant: CCO
Agent: [Pd]
Product: Cc1cc(N)c(N)cc1C
Reaction time: 2 h
Yield: 96 %

Procedure:
A mixture of 4,6-dimethyl-2-nitroaniline (1.66 g, 10.0 mmole) and 10% Pd/C (200 mg) in ethanol (35 mL) was hydrogenated for 2 h at room temperature under 25 psi H2. The catalyst was removed by filtration with celite and the solvent was removed by rota-evaporation to give 1.300 g (96%) of 1,2-diamino-4,5-dimethylbenzene as a brown solid. 1H NMR (CDCl3): 6.449 (s, 1H), 6.469 (s, 1H), 3.327 (br, 2H), 3.259 (br, 2H), 2.190 (s, 3H), 2.159 (s, 3H).
Reaction SMILES: CO[C:3](=[O:13])[C:4]1[C:9]([Cl:10])=[CH:8][CH:7]=[CH:6][C:5]=1[CH2:11]Br.[CH3:14][C:15]1[CH:22]=[CH:21][C:18]([CH2:19][NH2:20])=[CH:17][CH:16]=1.C([O-])([O-])=O.[K+].[K+].C(OCC)(=O)C>C1(C)C=CC=CC=1.CCCCCC>[Cl:10][C:9]1[CH:8]=[CH:7][CH:6]=[C:5]2[C:4]=1[C:3](=[O:13])[N:20]([CH2:19][C:18]1[CH:21]=[CH:22][C:15]([CH3:14])=[CH:16][CH:17]=1)[CH2:11]2
Reactant: Cc1ccc(CN)cc1
Reactant: COC(=O)c1c(Cl)cccc1CBr
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CCOC(C)=O
Solvent: Cc1ccccc1
Solvent: CCCCCC
Product: Cc1ccc(CN2Cc3cccc(Cl)c3C2=O)cc1
Temperature: 100 °C
Reaction time: 2 h
Yield: 44.2 %

Procedure:
A mixture of 2-bromomethyl-6-chloro-benzoic acid methyl ester (0.132 g, 0.5 mmol,), 4-methyl benzylamine (0.102 mL, 0.8 mmol), and K2CO3 (0.276 g, 2.0 mmol) in toluene (5 mL) was heated with stirring at 100° C. for 2 h. Workup and silica gel column chromatography using 30% ethyl acetate in hexane afforded 7-chloro-2-(4-methyl-benzyl) 2,3-dihydro-isoindol-1-one (0.06 g, 34%). 1H NMR (300 MHz, CDCl3): δ (ppm) 4.22 (s, 2H), 4.78 (s, 2H), 7.12-7.46 (m, 7H). GC-MS: m/z 271 (M)+.
Reaction SMILES: [CH:1]1([C:4]([C:6]2[CH:11]=[CH:10][C:9](F)=[CH:8][CH:7]=2)=O)[CH2:3][CH2:2]1.[CH2:13]([C:15]1[NH:16][CH:17]=[CH:18][N:19]=1)[CH3:14]>>[CH2:13]([C:15]1[N:19]2[CH2:2][CH2:3][CH:1]=[C:4]([C:6]3[CH:7]=[CH:8][C:9]([N:16]4[CH:17]=[CH:18][N:19]=[C:15]4[CH2:13][CH3:14])=[CH:10][CH:11]=3)[C:18]2=[CH:17][N:16]=1)[CH3:14]
Reactant: O=C(c1ccc(F)cc1)C1CC1
Reactant: CCc1ncc[nH]1
Product: CCc1nccn1-c1ccc(C2=CCCn3c2cnc3CC)cc1

Procedure:
Combine 155 g of (0.94 mol) of cyclopropyl-(4-fluorophenyl)methanone with 300 g (3.1 mol) of 2-ethylimidazole and heat to 175° C. under argon for 18 hr. The title compound is isolated by column chromatography on 1500 g of silica gel using 2% methanol/methylene chloride as solvent.
Reaction SMILES: [Cl-].[Li+].[CH3:3][O:4][C:5]([CH2:7]P(OC)(OC)=O)=[O:6].C1CCN2C(=NCCC2)CC1.[CH3:25][C:26]([C:28]1[CH:33]=[CH:32][CH:31]=[C:30]([O:34][CH2:35][C:36]2[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=2)[CH:29]=1)=O>CC#N.CCOC(C)=O>[C:36]1([CH2:35][O:34][C:30]2[CH:29]=[C:28](/[C:26](/[CH3:25])=[CH:7]/[C:5]([O:4][CH3:3])=[O:6])[CH:33]=[CH:32][CH:31]=2)[CH:37]=[CH:38][CH:39]=[CH:40][CH:41]=1
Reactant: COC(=O)CP(=O)(OC)OC
Reactant: CC(=O)c1cccc(OCc2ccccc2)c1
Agent: [Cl-]
Agent: [Li+]
Solvent: C1CCC2=NCCCN2CC1
Solvent: CCOC(C)=O
Solvent: CC#N
Product: COC(=O)/C=C(\C)c1cccc(OCc2ccccc2)c1
Temperature: 100 °C
Reaction time: 8 h
Yield: 36.2 %

Procedure:
To a suspension of lithium chloride (0.28 g, 6.6 mmol) in MeCN (9 mL), were added trimethyl phosphonoacetate (available from Aldrich) (0.76 mL, 5.3 mmol), DBU (0.79 mL, 5.3 mmol), and 3-benzyloxyacetophenone (available from Aldrich) (1.00 g, 4.4 mmol). The mixture was stirred overnight at reflux (100° C.), cooled to room temperature, diluted with EtOAc, washed with water and brine, dried (MgSO4), and concentrated. The crude product was chromatographed on silica gel (0-10% EtOAc/hexane) to afford 42.1 (0.45 g, 36%) as a colorless oil.
Reaction SMILES: [N:1]1([CH2:5][CH2:6][N:7]2[CH:11]=[C:10]([C:12]3[CH:17]=[CH:16][C:15]([F:18])=[C:14]([CH3:19])[CH:13]=3)[N:9]=[C:8]2[CH:20]2[CH2:25][CH2:24][N:23]([C:26]3[N:31]=[CH:30][N:29]=[C:28]([NH2:32])[C:27]=3Br)[CH2:22][CH2:21]2)[CH2:4][CH2:3][CH2:2]1.[N:34]1[CH:39]=[CH:38][CH:37]=[C:36](B(O)O)[CH:35]=1>>[N:1]1([CH2:5][CH2:6][N:7]2[CH:11]=[C:10]([C:12]3[CH:17]=[CH:16][C:15]([F:18])=[C:14]([CH3:19])[CH:13]=3)[N:9]=[C:8]2[CH:20]2[CH2:25][CH2:24][N:23]([C:26]3[N:31]=[CH:30][N:29]=[C:28]([NH2:32])[C:27]=3[C:36]3[CH:35]=[N:34][CH:39]=[CH:38][CH:37]=3)[CH2:22][CH2:21]2)[CH2:4][CH2:3][CH2:2]1
Reactant: Cc1cc(-c2cn(CCN3CCC3)c(C3CCN(c4ncnc(N)c4Br)CC3)n2)ccc1F
Reactant: OB(O)c1cccnc1
Product: Cc1cc(-c2cn(CCN3CCC3)c(C3CCN(c4ncnc(N)c4-c4cccnc4)CC3)n2)ccc1F

Procedure:
The title compound was prepared according to the procedure described for the preparation of compound “8” by using 6-{4-[1-(2-azetidin-1-yl-ethyl)-4-(4-fluoro-3-methyl-phenyl)-1H-imidazol-2-yl]-piperidin-1-yl}-5-bromo-pyrimidin-4-ylamine and pyridin-3-ylboronic acid as the starting materials. LC-MS (M+H=513, obsd=513).
Reaction SMILES: [NH:1]1[CH2:6][CH2:5][C:4](=[N:7][OH:8])[CH2:3][CH2:2]1.CS(O[CH2:14][CH:15]1[CH2:19][CH2:18][CH2:17][O:16]1)(=O)=O.C(=O)([O-])[O-].[K+].[K+]>C(C(C)=O)C(C)C>[O:16]1[CH2:17][CH2:18][CH2:19][CH:15]1[CH2:14][N:1]1[CH2:6][CH2:5][C:4](=[N:7][OH:8])[CH2:3][CH2:2]1
Reactant: CS(=O)(=O)OCC1CCCO1
Reactant: ON=C1CCNCC1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC(=O)CC(C)C
Product: ON=C1CCN(CC2CCCO2)CC1
Reaction time: 48 h
Yield: 535.9 %

Procedure:
A mixture of piperid-4-one oxime (46 g; 0.04 moles), 2-tetrahydrofurylmethyl methanesulphonate (79.3 g; 0.44 moles) and anhydrous potassium carbonate (56.5 g; 0.40 moles) in methyl isobutyl ketone (625 ml), was boiled under reflux with stirring for 48 hours. After cooling, the reaction mixture was washed with brine, dried (Na2SO4), and the solvent removed in vacuo. The residue was crystallised from diisopropyl ether to give 1-(2-tetrahydrofurylmethyl)-piperid-4-one oxime (42.5 g), m.p. 104°-106°.
Reaction SMILES: C[Al](C)C.[CH3:5][O:6][C:7]1[CH:12]=[C:11]([CH3:13])[N:10]=[C:9]([NH:14][C:15]([NH:17][S:18]([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][C:22]=2[C:27](OC)=[O:28])(=[O:20])=[O:19])=[O:16])[N:8]=1>C1(C)C=CC=CC=1>[CH3:5][O:6][C:7]1[CH:12]=[C:11]([CH3:13])[N:10]=[C:9]([NH:14][C:15]([NH:17][S:18]([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][C:22]=2[C:27]([S:18][CH2:21][CH2:22][CH2:23][CH3:24])=[O:28])(=[O:19])=[O:20])=[O:16])[N:8]=1
Reactant: COC(=O)c1ccccc1S(=O)(=O)NC(=O)Nc1nc(C)cc(OC)n1
Agent: C[Al](C)C
Solvent: Cc1ccccc1
Product: CCCCSC(=O)c1ccccc1S(=O)(=O)NC(=O)Nc1nc(C)cc(OC)n1
Temperature: 80 °C
Yield: 109.6 %

Procedure:
Trimethylaluminum (1.5 ml) (2 M) was charged via syringe to 5.0 ml dry toluene under nitrogen atmosphere and 0.54 g (0.006 mole) N-butanethiol in 2.0 ml toluene was added dropwise. N-[(4-methoxy-6-methylpyrimidin-2-yl)aminocarbonyl]-2-methoxycarbonylbenzenesulfonamide (0.95 g) was added portionwise and the mixture warmed to 80° C. for 3 hr. After cooling to room temperature, the mixture was quenched with 25 ml of 10% HCl. Methylene chloride was added, separated, dried over magnesium sulfate, filtered and evaporated to give a crude oil. Trituration with hexanes gave 0.6 g white solid, m.p. 115°-120° C., showing infrared absorption peaks at 1725, 1680, 1600, 1560 cm-1 consistent for N-[(4-methoxy-6-methylpyrimidin-2-yl)aminocarbonyl]-2-(N-butylthio)carbonylbenzenesulfonamide.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([CH:10]=CC2C=CC=CC=2)[C:5](=[O:9])[N:6]([CH3:8])[N:7]=1.CC1C=CC=C(C)N=1.I([O-])(=O)(=O)=[O:27].[Na+]>O1CCOCC1.O.[Os](=O)(=O)(=O)=O>[Cl:1][C:2]1[CH:3]=[C:4]([CH:10]=[O:27])[C:5](=[O:9])[N:6]([CH3:8])[N:7]=1
Reactant: [O-][I+3]([O-])([O-])[O-]
Reactant: Cn1nc(Cl)cc(C=Cc2ccccc2)c1=O
Agent: O=[Os](=O)(=O)=O
Agent: [Na+]
Solvent: Cc1cccc(C)n1
Solvent: O
Solvent: C1COCCO1
Product: Cn1nc(Cl)cc(C=O)c1=O
Temperature: 25 °C
Reaction time: 3 h
Yield: 47.7 %

Procedure:
A mixture of 6-chloro-2-methyl-4-styrylpyridazin-3(2H)-one (6 g, 24.32 mmol, Preparation #29), 4% aqueous osmium(VIII) oxide (0.1 mL, 1.216 mmol, Alfa-Aeser), 2,6-dimethylpyridine (5.21 g, 48.6 mmol, Aldrich) and sodium periodate (20.81 g, 97 mmol, Spectrochem) in aqueous dioxane (75%, 80 mL) was stirred at RT for about 3 h. The reaction mixture was diluted with water and the product extracted with EtOAc (5×60 mL). The combined organic layers were dried over sodium sulphate and evaporated under reduced pressure. The residue obtained was purified by silica gel (60-120) column chromatography by eluting with 30-50% EtOAc in hexane to afford 6-chloro-2-methyl-3-oxo-2,3-dihydropyridazine-4-carbaldehyde 2 g (47.7%) as pale yellow solid; 1H NMR (400 MHz, CDCl3) δ 10.359 (s, 1H), 7.658 (s, 1H), 3.846 (s, 3H); MS m/z: 170.9 (M−H)−
Reaction SMILES: [CH3:1][CH:2]([O:5][CH2:6][C:7]([O:9][CH3:10])=[O:8])[C:3]#[CH:4].C[OH:12]>C([O-])(=O)C.[Hg+2].C([O-])(=O)C>[CH3:1][CH:2]([O:5][CH2:6][C:7]([O:9][CH3:10])=[O:8])[C:3](=[O:12])[CH3:4]
Reactant: C#CC(C)OCC(=O)OC
Reactant: CO
Agent: CC(=O)[O-]
Agent: [Hg+2]
Product: COC(=O)COC(C)C(C)=O

Procedure:
The product from Example 84A (20 g, 0.14 mol) in methanol (700 mL) was treated with mercury(II) acetate (4.6 g, 0.014 mol), heated to reflux for 1 hour, concentrated to approximately 100 mL total volume, treated with 1M HCl (100 mL) and extracted with dichloromethane (3×, 100 mL). The extractions were combined, dried (MgSO4), filtered and concentrated to provide the title compound.
Reaction SMILES: [C:1]([O:4][C:5]1[CH:22]=[CH:21][C:20]2[C@@H:19]3[C@H:10]([C@H:11]4[C@@:15]([CH2:17][CH2:18]3)([CH3:16])[C@@H:14]([OH:23])[CH2:13][CH2:12]4)[CH2:9][CH2:8][C:7]=2[CH:6]=1)(=[O:3])[CH3:2].[C:24](Cl)(=[O:31])[C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1.CO>N1C=CC=CC=1.O>[C:1]([O:4][C:5]1[CH:22]=[CH:21][C:20]2[C@@H:19]3[C@H:10]([C@H:11]4[C@@:15]([CH2:17][CH2:18]3)([CH3:16])[C@@H:14]([O:23][C:24](=[O:31])[C:25]3[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=3)[CH2:13][CH2:12]4)[CH2:9][CH2:8][C:7]=2[CH:6]=1)(=[O:3])[CH3:2]
Reactant: O=C(Cl)c1ccccc1
Reactant: CC(=O)Oc1ccc2c(c1)CC[C@@H]1[C@@H]2CC[C@]2(C)[C@@H](O)CC[C@@H]12
Solvent: CO
Solvent: O
Solvent: c1ccncc1
Product: CC(=O)Oc1ccc2c(c1)CC[C@@H]1[C@@H]2CC[C@]2(C)[C@@H](OC(=O)c3ccccc3)CC[C@@H]12
Yield: 100 %

Procedure:
3-Acetoxy-oestra-1,3,5(10)-trien-17β-ol (500 mg., 1.6 mmole) in pyridine (2 ml.) was treated with benzoyl chloride (1.0 ml.) at room temperature for 16 hr. The stirred mixture was then slowly diluted with water (10 ml.), followed by methanol (5 ml.). The crystalline precipitate was filtered off, washed with water and dried to give the title compound (665 mg., 100%), m.p. 148.5°-150.5°.
Reaction SMILES: P([O:5][C@@H:6]1[C@@H:10]([CH2:11][OH:12])[O:9][C@@H:8]([N:13]2[C:23]3[N:22]=[C:20]([NH2:21])[NH:19][C:17](=[O:18])[C:16]=3[N:15]=[CH:14]2)[C@@H:7]1[OH:24])(O)(O)=O.P(O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C2N=C(N)NC(=O)C=2N=C1)(O)(O)=O.[C@@H]1(N2C3N=C(N)NC(=O)C=3N=C2)O[C@H](CO)[C@@H](O)[C@H]1O.[C:69](Cl)([C:82]1[CH:87]=[CH:86][CH:85]=[CH:84][CH:83]=1)([C:76]1[CH:81]=[CH:80][CH:79]=[CH:78][CH:77]=1)[C:70]1[CH:75]=[CH:74][CH:73]=[CH:72][CH:71]=1>N1C=CC=CC=1>[C:69]([CH:11]([OH:12])[C@H:10]1[O:9][C@@H:8]([N:13]2[C:23]3[N:22]=[C:20]([NH2:21])[NH:19][C:17](=[O:18])[C:16]=3[N:15]=[CH:14]2)[C@H:7]([OH:24])[C@@H:6]1[OH:5])([C:70]1[CH:75]=[CH:74][CH:73]=[CH:72][CH:71]=1)([C:82]1[CH:83]=[CH:84][CH:85]=[CH:86][CH:87]=1)[C:76]1[CH:77]=[CH:78][CH:79]=[CH:80][CH:81]=1
Reactant: ClC(c1ccccc1)(c1ccccc1)c1ccccc1
Reactant: Nc1nc2c(ncn2[C@@H]2O[C@H](CO)[C@@H](OP(=O)(O)O)[C@H]2O)c(=O)[nH]1
Agent: Nc1nc2c(ncn2[C@@H]2O[C@H](CO)[C@@H](O)[C@H]2O)c(=O)[nH]1
Agent: Nc1nc2c(ncn2[C@@H]2O[C@H](CO)[C@@H](O)[C@H]2OP(=O)(O)O)c(=O)[nH]1
Solvent: c1ccncc1
Product: Nc1nc2c(ncn2[C@@H]2O[C@H](C(O)C(c3ccccc3)(c3ccccc3)c3ccccc3)[C@@H](O)[C@H]2O)c(=O)[nH]1

Procedure:
Guanosine 3'-monophosphate (3'-GMP), a compound of formula (I) in which Y is H2PO3 and X and Z are hydrogen atoms, and guanosine 2'-monophosphate (2'-GMP), a compound of formula (I) in which X is H2PO3 and Z and Y are hydrogen atoms, can be obtained in the following manner in accordance with the method of Brown and Todd [D. M. Brown and A. R. Todd, J. Chem. Soc., 44 (1952)]. Specifically, guanosine and trityl chloride are reacted in anhydrous pyridine at 60° C. for 3 days to obtain 5'-tritylguanosine as a result of selective tritylation of the 5'-position. The resulting 5'-tritylguanosine is dissolved in pyridine, and while cooling the solution at -20° C., diphenylphosphoryl chloride was added to obtain a mixture of a trityl derivative of 2'-monophosphate of guanosine and 3'-monophosphate of guanosine. The mixture is dissolved in 80% acetic acid, and the solution is heated under reflux to remove the trityl group to obtain a mixture of 2'-GMP and 3'-GMP. The mixture is charged onto a column of Dowex 1® (formic acid type). The column is eluted with 0.1N formic acid to obtain guanosine 2'-monophosphate as an eluate, and with 1N formic acid to obtain guanosine 3'-monophosphate as an eluate. These eluates are each concentrated, lyophilized and recrystallized from water to separate the desired 2'-GMP and 3'-GMP.
Reaction SMILES: [CH3:1][C:2]1([CH3:25])[C:6]([C:7]2[CH:8]=[C:9]([CH:14]=[CH:15][C:16]=2OS(C(F)(F)F)(=O)=O)[C:10]([O:12][CH3:13])=[O:11])=[CH:5][CH2:4][CH2:3]1.C(=O)([O-])[O-].[K+].[K+].[F:32][C:33]1[C:34](B(O)O)=[CH:35][C:36]([O:39][CH3:40])=[N:37][CH:38]=1>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>[CH3:1][C:2]1([CH3:25])[C:6]([C:7]2[CH:8]=[C:9]([CH:14]=[CH:15][C:16]=2[C:34]2[C:33]([F:32])=[CH:38][N:37]=[C:36]([O:39][CH3:40])[CH:35]=2)[C:10]([O:12][CH3:13])=[O:11])=[CH:5][CH2:4][CH2:3]1
Reactant: COc1cc(B(O)O)c(F)cn1
Reactant: COC(=O)c1ccc(OS(=O)(=O)C(F)(F)F)c(C2=CCCC2(C)C)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: [K+]
Product: COC(=O)c1ccc(-c2cc(OC)ncc2F)c(C2=CCCC2(C)C)c1
Temperature: 87 °C
Reaction time: 8 h
Yield: 78 %

Procedure:
To a flask with methyl 3-(5,5-dimethylcyclopent-1-enyl)-4-(trifluoromethylsulfonyloxy)benzoate C.6 (404 mg, 1068 μmol) was added Pd(PPh3)4 (123 mg, 107 μmol), potassium carbonate (443 mg, 3203 μmol), 5-fluoro-2-methoxypyridin-4-ylboronic acid L.1 (456 mg, 2669 μmol, commercially available from Asymchem). The mixture was then degassed, and DMF (3 mL) was added. The reaction was stirred overnight at 87° C. and worked up with EtOAc and water. Silica gel chromatography (0-50% EtOAc/Hexanes) afforded methyl 3-(5,5-dimethylcyclopent-1-enyl)-4-(5-fluoro-2-methoxypyridin-4-yl)benzoate L.2 295 mg (78%).