Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [F:1][C:2]([F:12])([F:11])[C:3]1[CH:7]=[C:6]([C:8](Cl)=[O:9])[NH:5][N:4]=1.[H-].[H-].[H-].[H-].[Li+].[Al+3].CO.CCOC(C)=O>C1COCC1>[F:12][C:2]([F:1])([F:11])[C:3]1[CH:7]=[C:6]([CH2:8][OH:9])[NH:5][N:4]=1
Reactant: O=C(Cl)c1cc(C(F)(F)F)n[nH]1
Agent: [Al+3]
Agent: [H-]
Agent: [Li+]
Solvent: CO
Solvent: C1CCOC1
Solvent: CCOC(C)=O
Product: OCc1cc(C(F)(F)F)n[nH]1
Temperature: 25 °C
Reaction time: 48 h

Procedure:
3-(Trifluoromethyl)pyrazole-5-carbonyl chloride (500 mg, 2.52 mmol) was dissolved in THF (10 mL). The reaction mixture was put under a N2 atmosphere and LiAlH4 (191 mg, 5.03 mmol) was added portionwise. The reaction mixture was stirred at RT for 2 days before adding MeOH (10 mL). The reaction mixture was concentrated in vacuo to give a grey solid. EtOAc (20 mL) was added and the crude reaction product stirred at RT for 30 min. The resulting solid was filtered off and the filtrate concentrated in vacuo to give the crude product which was used without further purification in the next step.
Reaction SMILES: [Br:1][C:2]1[C:7]2[N:8]([C:29]3[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=3)[C:9]([C@@H:11]([NH:13][C:14]3[N:22]=[CH:21][N:20]=[C:19]4[C:15]=3[N:16]=[CH:17][N:18]4C3CCCCO3)[CH3:12])=[N:10][C:6]=2[CH:5]=[CH:4][CH:3]=1>Cl>[Br:1][C:2]1[C:7]2[N:8]([C:29]3[CH:30]=[CH:31][CH:32]=[CH:33][CH:34]=3)[C:9]([C@@H:11]([NH:13][C:14]3[N:22]=[CH:21][N:20]=[C:19]4[C:15]=3[N:16]=[CH:17][NH:18]4)[CH3:12])=[N:10][C:6]=2[CH:5]=[CH:4][CH:3]=1
Reactant: C[C@H](Nc1ncnc2c1ncn2C1CCCCO1)c1nc2cccc(Br)c2n1-c1ccccc1
Agent: Cl
Product: C[C@H](Nc1ncnc2[nH]cnc12)c1nc2cccc(Br)c2n1-c1ccccc1
Reaction time: 0.25 h
Yield: 101.7 %

Procedure:
[(S)-1-(7-Bromo-1-phenyl-1H-benzoimidazol-2-yl)ethyl][9-(tetrahydropyran-2-yl)-9H-purin-6-yl]amine (60 mg, 0.12 mmol) was dissolved in HCl (1 mL, 1M in MeOH) and the resulting solution was stirred for 15 min. The solvent was removed in vacuo and the residue was crystallised from hot IPA to give 292 as white crystals (53 mg, 98%). 1H NMR (DMSO-d6, 400 MHz): δ 8.64-8.47 (2H, m), 7.82-7.76 (2H, m), 7.74-7.50 (5H, m), 7.44 (1H, t, J=8.1 Hz), 5.53-5.41 (1H, m), 1.84 (3H, d, J=7.0 Hz). LCMS (Method K): RT 3.69 min; m/z [M+H]+ 434/436
Reaction SMILES: [CH3:1][N:2]([CH3:23])[C:3]([C:5]1[N:6]=[CH:7][C:8]([O:11][C:12]2[CH:13]=[C:14]([CH:19]=[C:20]([OH:22])[CH:21]=2)[C:15]([O:17][CH3:18])=[O:16])=[N:9][CH:10]=1)=[O:4].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[CH3:43][C:44]([O:47][CH2:48][C@H:49](O)[CH3:50])([CH3:46])[CH3:45].CCOC(/N=N/C(OCC)=O)=O>C1COCC1>[CH3:23][N:2]([CH3:1])[C:3]([C:5]1[N:6]=[CH:7][C:8]([O:11][C:12]2[CH:13]=[C:14]([CH:19]=[C:20]([O:22][C@@H:49]([CH3:50])[CH2:48][O:47][C:44]([CH3:46])([CH3:45])[CH3:43])[CH:21]=2)[C:15]([O:17][CH3:18])=[O:16])=[N:9][CH:10]=1)=[O:4]
Reactant: COC(=O)c1cc(O)cc(Oc2cnc(C(=O)N(C)C)cn2)c1
Reactant: C[C@@H](O)COC(C)(C)C
Agent: CCOC(=O)/N=N/C(=O)OCC
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: C1CCOC1
Product: COC(=O)c1cc(Oc2cnc(C(=O)N(C)C)cn2)cc(O[C@@H](C)COC(C)(C)C)c1
Temperature: 0 °C

Procedure:
To methyl 3-[5-(dimethylcarbamoyl)pyrazin-2-yl]oxy-5-hydroxy-benzoate (10 g, 32 mmol) was added triphenylphosphine (10.3 g, 39.4 mmol), THF (100 mL) and (2R)-1-[(2-methylpropan-2-yl)oxy]propan-2-ol (CAS no. 136656-73-0) (5.21 g, 39.4 mmol). The resulting slurry was cooled to 0° C. and diethylazodicarboxylate (50% w/v in toluene, 13.7 mL, 39.4 mmol) was charged dropwise keeping the temperature below 10° C. After 2 hours the solvent was evaporated under reduced pressure and taken up with ethyl acetate (23 mL). A solid crashed out which was filtered and the mother liquors were evaporated under reduced pressure, taken up into ethyl acetate (23 mL) and isohexane (53 mL) and the resulting solid filtered, the mother liquors were evaporated under reduced pressure and the resulting residue was purified by flash chromatography eluting with 80% ethyl acetate/ 20% isohexane to afford the product (13.5 g).
Reaction SMILES: O1CCOCC1.[CH2:7]=[CH:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH3:14].CN(C)P(N(C)C)(N(C)C)=O.[C:26]1([NH:32]O)[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1>C1(C)C=CC=CC=1>[C:26]1([NH:32][CH2:7]/[CH:8]=[CH:9]/[CH2:10][CH2:11][CH2:12][CH2:13][CH3:14])[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1
Reactant: ONc1ccccc1
Reactant: C=CCCCCCC
Solvent: Cc1ccccc1
Solvent: CN(C)P(=O)(N(C)C)N(C)C
Solvent: C1COCCO1
Product: CCCCC/C=C/CNc1ccccc1
Yield: 95 %

Procedure:
A stirred mixture containing dioxane (12 mL), 3 mL of 1-octene, 1 g of 4A Molecular Sieves, and 0.051 g (0.11 mmol) of (2,6-dipicolinato)MoO2 (hexamethyl phosphoramide) is heated at reflux (ca. 100° C.) under a nitrogen atomosphere while a toluene solution (50 mL) of N-phenyl hydroxylamine (1.26 g, 11.6 mmol) is added dropwise over a 24 hr period. After heating an additional 6-12 hr, the mixture was allowed to cool and the volatiles were removed by evaporation at reduced pressure and the residue chromatographed over silica gel. Elution with pentane afforded phenyl trans-2-octenyl amine (>95% one isomer by NMR, GC/MS) in 20-30% yield based on the hydroxylamine. Later fractions contained aniline, azobenzene and azoxybenzene.
Reaction SMILES: [CH3:1][CH:2]1[C:6](=[O:7])[CH2:5][CH2:4][C:3]1=[O:8].[OH-].[K+].I[CH3:12]>O1CCOCC1.O>[CH3:1][C:2]1([CH3:12])[C:6](=[O:7])[CH2:5][CH2:4][C:3]1=[O:8]
Reactant: CC1C(=O)CCC1=O
Reactant: CI
Agent: [K+]
Agent: [OH-]
Solvent: O
Solvent: C1COCCO1
Product: CC1(C)C(=O)CCC1=O
Temperature: 25 °C
Reaction time: 8 h
Yield: 67.7 %

Procedure:
A mixture of 2-methylcyclopentane-1,3-dione (49.98 g, 446 mmol), potassium hydroxide (25.5 g, 455 mmol) and iodomethane (30.1 mL, 481 mmol) in dioxane (390 mL) and water (130 mL) was heated to reflux for 5 h. A biphasic mixture of potassium hydroxide (10.4 g), iodomethane (12.5 mL), water (26 mL) and dioxane (78 mL) was added. The mixture was heated at reflux for 3 additional hours and then stirred at ambient temperature overnight. Another portion of a biphasic mixture of potassium hydroxide (10.4 g), iodomethane (12.5 mL), water (26 mL) and dioxane (78 mL) was added. The mixture was heated at reflux for 3 h, cooled to room temperature and extracted with ether (600 mL, then 2×400 mL). The combined extracts were concentrated using a rotavap while keeping the bath temperature at or below room temperature to prevent loss of volatile product. The residue was treated with 10% hydrochloric acid (250 mL) and placed in a 120° C. oil bath until it started to boil (˜15 min). The mixture was cooled with an ice-water bath, diluted with water (250 mL) and treated with careful addition of sodium carbonate until carbon dioxide release stopped. The pH of the solution was 8-9. The mixture was extracted with dichloromethane (4×200 mL). The combined extracts were dried (MgSO4), filtered and concentrated while keeping water bath at or below room temperature. The residue was further dried under vacuum briefly to remove residual solvent to give 2,2-dimethylcyclopentane-1,3-dione as tan solid (38.1 g, 68% yield). 1H NMR (400 MHz, chloroform-d) δ ppm 2.81 (4H, s), 1.16 (6H, s); LC retention time: 0.990 min (analytical HPLC Method F).
Reaction SMILES: C([Li])CCC.Br[C:7]1[O:8][CH:9]=[CH:10][C:11]=1[Br:12].[CH2:13]1[O:15][CH2:14]1.[Cl-].[NH4+]>C(OCC)C>[Br:12][C:11]1[CH:10]=[CH:9][O:8][C:7]=1[CH2:13][CH2:14][OH:15]
Reactant: Brc1ccoc1Br
Reactant: C1CO1
Agent: [Cl-]
Agent: [Li]CCCC
Agent: [NH4+]
Solvent: CCOCC
Product: OCCc1occc1Br
Temperature: 25 °C
Reaction time: 0.25 h

Procedure:
n-Butyllithium (2.5M in hexanes, 12.9 mL) was added to a solution of 2,3-dibromofuran (6.63 g) in diethyl ether (40 mL) at −78° C. under nitrogen and the mixture was stirred for 15 minutes. A solution of ethylene oxide (15 mL) in diethyl ether (40 mL) was then added. The reaction mixture was stirred for a further 10 minutes then warmed to room temperature and stirred for 30 minutes. Saturated aqueous ammonium chloride was added and the organic layer was separated, dried (MgSO4) and filtered. The filtrate was evaporated to dryness and the residue was purified by chromatography on silica, eluting with a mixture of ethyl acetate and cyclohexane with a gradient of 5-25% to give 2-(3-bromofuran-2-yl)-ethanol (3.81 g) as a yellow oil.
Reaction SMILES: [CH2:1]([C:3]([OH:33])([CH2:31][CH3:32])[CH2:4][CH2:5][CH2:6][CH:7]([C:9]1[CH:10]=[C:11]([CH:28]=[CH:29][CH:30]=1)[O:12][CH2:13][C:14]1[CH:15]=[C:16]([C:24](OC)=[O:25])[C:17](=[CH:22][CH:23]=1)[C:18](OC)=[O:19])[CH3:8])[CH3:2].[BH4-].[Li+].[Cl-].[NH4+]>C1COCC1>[OH:25][CH2:24][C:16]1[CH:15]=[C:14]([CH:23]=[CH:22][C:17]=1[CH2:18][OH:19])[CH2:13][O:12][C:11]1[CH:10]=[C:9]([CH:7]([CH3:8])[CH2:6][CH2:5][CH2:4][C:3]([CH2:1][CH3:2])([OH:33])[CH2:31][CH3:32])[CH:30]=[CH:29][CH:28]=1
Reactant: CCC(O)(CC)CCCC(C)c1cccc(OCc2ccc(C(=O)OC)c(C(=O)OC)c2)c1
Agent: [BH4-]
Agent: [Cl-]
Agent: [Li+]
Solvent: C1CCOC1
Product: CCC(O)(CC)CCCC(C)c1cccc(OCc2ccc(CO)c(CO)c2)c1

Procedure:
220 mg (0.48 mmol) of dimethyl 4-[3-(5-ethyl-5-hydroxy-1-methylheptyl)phenoxymethyl]phthalate are dissolved in 15 ml of anhydrous THF. 42 mg (1.9 mmol) of lithium borohydride are then added and the reaction medium is heated under reflux for 12 hours. After cooling, treating with a saturated ammonium chloride solution and extracting with ethyl acetate, the organic phase is dried and concentrated under reduced pressure. The residue is then purified by chromatography on a silica column. A colourless oil is obtained (m=132 mg; Y=75%).
Reaction SMILES: [F:1][C@@H:2]1[CH2:7][C@H:6]2[C@H:8]3[C@H:18]([CH2:19][CH2:20][C@:4]2([CH3:5])[C:3]1=[O:25])[C@:16]1([CH3:17])[C:11](=[CH:12][C:13](=[O:22])[CH2:14][C@H:15]1[CH3:21])[C@@H:10]([CH3:23])[C:9]3=[CH2:24].ClC1C(=O)C(C#N)=C(C#N)C(=O)C=1Cl>O1CCOCC1>[F:1][C@@H:2]1[CH2:7][C@H:6]2[C@H:8]3[C@H:18]([CH2:19][CH2:20][C@:4]2([CH3:5])[C:3]1=[O:25])[C@:16]1([CH3:17])[C:11](=[CH:12][C:13](=[O:22])[CH:14]=[C:15]1[CH3:21])[C@@H:10]([CH3:23])[C:9]3=[CH2:24]
Reactant: C=C1[C@H](C)C2=CC(=O)C[C@@H](C)[C@]2(C)[C@H]2CC[C@]3(C)C(=O)[C@H](F)C[C@H]3[C@H]12
Agent: N#CC1=C(C#N)C(=O)C(Cl)=C(Cl)C1=O
Solvent: C1COCCO1
Product: C=C1[C@H](C)C2=CC(=O)C=C(C)[C@]2(C)[C@H]2CC[C@]3(C)C(=O)[C@H](F)C[C@H]3[C@H]12
Yield: 64.9 %

Procedure:
A mixture of 16α-fluoro-1β,6α-dimethyl-7-methylenandrost-4-ene-3,17-dione (344 mg) and dichlorodicyanobenzoquinone (363 mg) in dioxane (20 ml) is refluxed for about 15 hours. Then the resulting suspension is cooled, the precipitate filtered off and the filtrate evaporated in vacuo. The residue is dissolved in ethyl acetate, the organic layer washed with water, dried over sodium sulfate and the solvent removed under vacuum. The crude product is chromatographed on silica gel using hexane/ethyl acetate as eluant to yield 16α-fluoro-1,6α-dimethyl-7-methylenandrosta-1,4-diene-3,17-dione (222 mg).
Reaction SMILES: Br[C:2]1[CH:7]=[CH:6][C:5]([C@@H:8]([C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)[O:9][C@@H:10]([CH2:15][CH:16]([CH3:18])[CH3:17])[C:11]([O:13][CH3:14])=[O:12])=[CH:4][CH:3]=1.[N:25]1[C:34]2[C:29](=[CH:30][CH:31]=[CH:32][CH:33]=2)[CH:28]=[C:27](B(O)O)[CH:26]=1>>[CH3:17][CH:16]([CH3:18])[CH2:15][C@H:10]([O:9][C@H:8]([C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1)[C:5]1[CH:6]=[CH:7][C:2]([C:27]2[CH:26]=[N:25][C:34]3[C:29]([CH:28]=2)=[CH:30][CH:31]=[CH:32][CH:33]=3)=[CH:3][CH:4]=1)[C:11]([O:13][CH3:14])=[O:12]
Reactant: OB(O)c1cnc2ccccc2c1
Reactant: COC(=O)[C@H](CC(C)C)O[C@H](c1ccccc1)c1ccc(Br)cc1
Product: COC(=O)[C@H](CC(C)C)O[C@H](c1ccccc1)c1ccc(-c2cnc3ccccc3c2)cc1

Procedure:
Using the same procedure as described for example 36 step 2, methyl (2S)-2-{[(R)-(4-bromophenyl)(phenyl)methyl]oxy}-4-methylpentanoate (2.05 g, 5.25 mmol) and 3-quinolineboronic acid (1.0 g, 5.78 mmol) were coupled to give the title compound as an oil.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:11]=[C:10]2[C:6]([C:7]([CH2:18][C:19]3[N:24]=[C:23]([C:25](=[N:27][OH:28])[NH2:26])[CH:22]=[CH:21][CH:20]=3)=[C:8]([C:12]3[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=3)[NH:9]2)=[CH:5][CH:4]=1.[C:29](N1C=CN=C1)(N1C=CN=C1)=[S:30].C1CCN2C(=NCCC2)CC1>C(#N)C>[CH3:1][O:2][C:3]1[CH:11]=[C:10]2[C:6]([C:7]([CH2:18][C:19]3[N:24]=[C:23]([C:25]4[NH:26][C:29](=[S:30])[O:28][N:27]=4)[CH:22]=[CH:21][CH:20]=3)=[C:8]([C:12]3[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=3)[NH:9]2)=[CH:5][CH:4]=1
Reactant: S=C(n1ccnc1)n1ccnc1
Reactant: COc1ccc2c(Cc3cccc(C(N)=NO)n3)c(-c3ccccc3)[nH]c2c1
Solvent: C1CCC2=NCCCN2CC1
Solvent: CC#N
Product: COc1ccc2c(Cc3cccc(-c4noc(=S)[nH]4)n3)c(-c3ccccc3)[nH]c2c1
Temperature: 25 °C
Reaction time: 22 h
Yield: 101.2 %

Procedure:
Under an argon atmosphere, to a solution of 6-(6-methoxy-2-phenyl-1H-indol-3-ylmethyl)pyridine-2-carboxamidoxime (174 mg) in acetonitrile (3.7 mL) were added 1,1′-thiocarbonyldiimidazole (125 mg) and 1,8-diazabicyclo[5,4,0]-7-undecene (0.278 mL), and this mixture was stirred at room temperature for 22 hours. The reaction mixture was concentrated under reduced pressure. To the residue was added 10% aqueous citric acid solution, followed by extraction with ethyl acetate. The organic layer was washed with a saturated aqueous sodium hydrogen carbonate solution and saturated brine, dried over anhydrous sodium sulfate, and then concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluting solvent: methanol-ethyl acetate) to obtain the title compound (196 mg). 1H-NMR (DMSO-d6) δ ppm: 3.77 (3H, s), 4.33 (2H, s), 6.63 (1H, dd, J=2.3, 8.7 Hz), 6.88 (1H, d, J=2.3 Hz), 7.12 (1H, dd, J=2.3, 6.5 Hz), 7.28-7.39 (2H, m), 7.41-7.52 (2H, m), 7.68-7.79 (4H, m), 11.16 (1H, s). ESI-MS (m/z): 415 (M+H)+
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[O:12][N:11]=[CH:10][C:9]=1[C:13]([OH:15])=O.C(O)(=O)C(O)=O.[Cl:22][C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][C:24]=1[CH:29]1[CH2:33][CH2:32][NH:31][CH2:30]1>>[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[O:12][N:11]=[CH:10][C:9]=1[C:13]([N:31]1[CH2:32][CH2:33][CH:29]([C:24]2[CH:25]=[CH:26][CH:27]=[CH:28][C:23]=2[Cl:22])[CH2:30]1)=[O:15]
Reactant: O=C(O)c1cnoc1-c1ccccc1Cl
Reactant: Clc1ccccc1C1CCNC1
Agent: O=C(O)C(=O)O
Product: O=C(c1cnoc1-c1ccccc1Cl)N1CCC(c2ccccc2Cl)C1

Procedure:
The title compound was prepared from 5-(2-chlorophenyl)isoxazole-4-carboxylic acid (11.2 mg, 0.050 mmol) and 3-(2-chlorophenyl)pyrrolidine oxalate (16.3 mg, 0.060 mmol) as described in synthetic method C and thereafter purified by preparative HPLC method B to give a solid (4.0 mg). MS (pos) m/z 387.0 (M+H).
Reaction SMILES: [N:1]1([C:5]([C:7]2[O:8][C:9]3[C:15]([N:16]4[CH2:21][CH2:20][NH:19][CH2:18][CH2:17]4)=[CH:14][CH:13]=[CH:12][C:10]=3[CH:11]=2)=[O:6])[CH2:4][CH2:3][CH2:2]1.[CH3:22][O:23][C:24]1[CH:29]=[CH:28][CH:27]=[C:26]([CH:30]=[CH2:31])[N:25]=1.C(O)(=O)C>CO>[N:1]1([C:5]([C:7]2[O:8][C:9]3[C:15]([N:16]4[CH2:17][CH2:18][N:19]([CH2:31][CH2:30][C:26]5[CH:27]=[CH:28][CH:29]=[C:24]([O:23][CH3:22])[N:25]=5)[CH2:20][CH2:21]4)=[CH:14][CH:13]=[CH:12][C:10]=3[CH:11]=2)=[O:6])[CH2:4][CH2:3][CH2:2]1
Reactant: O=C(c1cc2cccc(N3CCNCC3)c2o1)N1CCC1
Reactant: C=Cc1cccc(OC)n1
Solvent: CO
Solvent: CC(=O)O
Product: COc1cccc(CCN2CCN(c3cccc4cc(C(=O)N5CCC5)oc34)CC2)n1
Temperature: 120 °C

Procedure:
Azetidin-1-yl(7-(piperazin-1-yl)benzofuran-2-yl)methanone (0.070 g, 0.25 mmol) was dissolved in methanol (1 mL). 2-Methoxy-6-vinylpyridine (0.066 g, 0.49 mmol) and acetic acid (0.014 mL, 0.25 mmol) were added. The mixture was heated by microwave irradiation to 120° C. for 10 h. The product was purified by preparative HPLC to give the title compound.
Reaction SMILES: [N+:1]([C:4]1[CH:17]=[CH:16][C:7]([O:8][C:9]([CH3:15])([CH3:14])[C:10]([O:12]C)=[O:11])=[CH:6][CH:5]=1)([O-:3])=[O:2].[OH-].[Na+].Cl>CO.O>[N+:1]([C:4]1[CH:5]=[CH:6][C:7]([O:8][C:9]([CH3:15])([CH3:14])[C:10]([OH:12])=[O:11])=[CH:16][CH:17]=1)([O-:3])=[O:2]
Reactant: COC(=O)C(C)(C)Oc1ccc([N+](=O)[O-])cc1
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: CO
Solvent: O
Product: CC(C)(Oc1ccc([N+](=O)[O-])cc1)C(=O)O
Temperature: 25 °C
Reaction time: 0.5 h

Procedure:
Methyl 2-(4-nitrophenoxy)isobutyrate was dissolved in methanol (50 mL) and water (50 mL). Sodium hydroxide (5 g) was added. The solution was stirred at rt for 30 min, then acidified with 1N HCl aq. to pH ˜3. The aq. Solution was extracted with ethyl acetate (2×100 mL). The organic layers were evaporated to give 2-(4-nitrophenoxy)isobutyric acid.
Reaction SMILES: [S:1]1[CH2:5][CH2:4][S:3][CH:2]1[CH2:6][CH2:7][CH:8]1[CH:19](/[CH:20]=[CH:21]/[CH:22]([OH:28])[CH2:23][CH2:24][CH2:25][CH2:26][CH3:27])[CH2:18][CH2:17][C:9]21[O:14][CH2:13][C:12]([CH3:16])([CH3:15])[CH2:11][O:10]2.C1(C)C=CC(S(O)(=O)=O)=CC=1.[O:40]1[CH:45]=[CH:44][CH2:43][CH2:42][CH2:41]1.C([O-])([O-])=O.[Na+].[Na+]>CCOCC>[S:1]1[CH2:5][CH2:4][S:3][CH:2]1[CH2:6][CH2:7][CH:8]1[CH:19](/[CH:20]=[CH:21]/[CH:22]([OH:28])[CH2:23][CH2:24][CH2:25][CH2:26][CH3:27])[CH2:18][CH2:17][C:9]21[O:14][CH2:13][C:12]([CH3:16])([CH3:15])[CH2:11][O:10]2.[O:40]1[CH2:41][CH2:42][CH2:43][CH2:44][CH:45]1[O:14][CH:9]1[CH2:17][CH2:18][CH2:19][CH2:20][O:10]1
Reactant: C1=COCCC1
Agent: CCCCCC(O)/C=C/C1CCC2(OCC(C)(C)CO2)C1CCC1SCCS1
Agent: Cc1ccc(S(=O)(=O)O)cc1
Agent: O=C([O-])[O-]
Solvent: CCOCC
Product: C1CCC(OC2CCCCO2)OC1
Temperature: 25 °C
Reaction time: 4 h

Procedure:
1.1 g (2.5 mmoles of 1-[7-[(1,3-dithia-2-cyclopentyl)-ethyl]-3,3-dimethyl-1,5-dioxaspiro[5,4]-dec-8-yl]-trans-1-octene-3-ol were dissolved in 20 ml of absolute ether, 20 mg of p-toluenesulfonic acid were added, 1.2 ml (13 mmoles) of dihydropyrane in 10 ml of absolute ether were added dropwise and the whole was stirred for 4 hours at room temperature. 0.2 ml of dihydropyrane was again added. The reaction mixture was allowed to stand overnight and was then stirred for 30 minutes with 0.5 g of solid Na2CO3. The suspension was filtered, the filtrate was concentrated under reduced pressure and the oil that had formed was eluted with cyclohexane-ethyl acetate (9:1) over a silica gel column.
Reaction SMILES: [OH:1][C:2]1[C:7]2[C:8]([CH3:20])=[C:9]([CH2:11][C:12]3[CH:17]=[CH:16][C:15]([O:18][CH3:19])=[CH:14][CH:13]=3)[O:10][C:6]=2[C:5]([Cl:21])=[CH:4][C:3]=1C(C)(C)C.C1(OC)C=CC=CC=1.[Cl-].[Al+3].[Cl-].[Cl-]>ClCCl>[OH:1][C:2]1[C:7]2[C:8]([CH3:20])=[C:9]([CH2:11][C:12]3[CH:17]=[CH:16][C:15]([O:18][CH3:19])=[CH:14][CH:13]=3)[O:10][C:6]=2[C:5]([Cl:21])=[CH:4][CH:3]=1
Reactant: COc1ccc(Cc2oc3c(Cl)cc(C(C)(C)C)c(O)c3c2C)cc1
Agent: [Al+3]
Agent: [Cl-]
Solvent: COc1ccccc1
Solvent: ClCCl
Product: COc1ccc(Cc2oc3c(Cl)ccc(O)c3c2C)cc1
Reaction time: 1 h

Procedure:
To a cold solution (0° C) of 4-hydroxy-7-chloro-5-t-butyl-2-(4'-methoxyphenylmethyl)-3-methylbenzofuran(165) (Example 43) (10 g, 27.8 mmol) in 500 mL dichloromethane was added 5 mL of anisole followed by aluminum chloride (13 g, 0.1 mol) in portions. The mixture was allowed to stir for 1 h and then poured onto ice. The mixture was extracted with dichloromethane, the organic extracts were dried, concentrated and chromatographed to give the title compound.
Reaction SMILES: [OH:1][CH:2]1[CH2:7][CH2:6][N:5]([C:8]([N:10]2[CH2:15][CH:14]([C:16]3[CH:21]=[CH:20][C:19]([O:22][C:23]([F:26])([F:25])[F:24])=[CH:18][CH:17]=3)[CH2:13][CH:12]([C:27](O)=[O:28])[CH2:11]2)=[O:9])[CH2:4][CH2:3]1.O[N:31]=[C:32]([CH:34]1[CH2:36][CH2:35]1)[NH2:33]>>[CH:34]1([C:32]2[N:33]=[C:27]([CH:12]3[CH2:13][CH:14]([C:16]4[CH:17]=[CH:18][C:19]([O:22][C:23]([F:26])([F:25])[F:24])=[CH:20][CH:21]=4)[CH2:15][N:10]([C:8]([N:5]4[CH2:4][CH2:3][CH:2]([OH:1])[CH2:7][CH2:6]4)=[O:9])[CH2:11]3)[O:28][N:31]=2)[CH2:36][CH2:35]1
Reactant: NC(=NO)C1CC1
Reactant: O=C(O)C1CC(c2ccc(OC(F)(F)F)cc2)CN(C(=O)N2CCC(O)CC2)C1
Product: O=C(N1CCC(O)CC1)N1CC(c2ccc(OC(F)(F)F)cc2)CC(c2nc(C3CC3)no2)C1

Procedure:
200 mg (0.480 mmol) of the compound from Example 63A and 96 mg (0.961 mmol) of N′-hydroxycyclopropanecarboximidamide were reacted according to the General Method 2. Yield: 130 mg (56% of theory).
Reaction SMILES: Cl.[CH2:2]([NH:6][C:7]1[C:15]2[C:10](=[CH:11][C:12]([Cl:22])=[C:13]([C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=3)[CH:14]=2)[N:9](COCC[Si](C)(C)C)[N:8]=1)[CH2:3][CH2:4][CH3:5]>CO>[CH2:2]([NH:6][C:7]1[C:15]2[C:10](=[CH:11][C:12]([Cl:22])=[C:13]([C:16]3[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=3)[CH:14]=2)[NH:9][N:8]=1)[CH2:3][CH2:4][CH3:5]
Reactant: CCCCNc1nn(COCC[Si](C)(C)C)c2cc(Cl)c(-c3ccccc3)cc12
Agent: Cl
Solvent: CO
Product: CCCCNc1n[nH]c2cc(Cl)c(-c3ccccc3)cc12
Temperature: 25 °C
Reaction time: 48 h
Yield: 109.3 %

Procedure:
0.7 ml of 2N HCl is added to a solution of 21 mg of butyl[6-chloro-5-phenyl-1-(2-(trimethylsilanyl)ethoxymethyl)-1H-indazol-3-yl]amine in 0.3 cm3 of methanol. The reaction medium is stirred at ambient temperature for 48 hours and at reflux for 1 hour, then evaporated. The solid obtained is dried under vacuum to give 16 mg of N-butyl-6-chloro-5-phenyl-1H-indazol-3-amine (yellow solid).
Reaction SMILES: [NH2:1][C:2]1[N:10]=[C:9]2[C:5]([NH:6][CH:7]=[N:8]2)=[C:4]([Cl:11])[N:3]=1.C/C(/O[Si](C)(C)C)=N\[Si](C)(C)C.[C:24]([O:32][C@H:33]1[C@@H:37]([O:38][C:39](=[O:46])[C:40]2[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=2)[C@@H:36](OC(=O)C)[O:35][C@@H:34]1[C:51]([NH:53][CH2:54][CH3:55])=[O:52])(=[O:31])[C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1.C(O[C@H]1[C@@H](OC(=O)C2C=CC=CC=2)[C@H](OC(=O)C)O[C@@H]1C(NCC)=O)(=O)C1C=CC=CC=1.FC(F)(F)S(O[Si](C)(C)C)(=O)=O>ClC(Cl)(Cl)C.C1(C)C=CC=CC=1.C(OCC)(=O)C>[C:39]([O:38][C@@H:37]1[C@H:33]([O:32][C:24](=[O:31])[C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)[C@@H:34]([C:51]([NH:53][CH2:54][CH3:55])=[O:52])[O:35][C@H:36]1[N:8]1[CH:7]=[N:6][C:5]2[C:9]1=[N:10][C:2]([NH2:1])=[N:3][C:4]=2[Cl:11])(=[O:46])[C:40]1[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=1
Reactant: CCNC(=O)[C@H]1O[C@H](OC(C)=O)[C@H](OC(=O)c2ccccc2)[C@@H]1OC(=O)c1ccccc1
Reactant: Nc1nc(Cl)c2[nH]cnc2n1
Agent: C/C(=N\[Si](C)(C)C)O[Si](C)(C)C
Agent: CCNC(=O)[C@H]1O[C@@H](OC(C)=O)[C@H](OC(=O)c2ccccc2)[C@@H]1OC(=O)c1ccccc1
Agent: C[Si](C)(C)OS(=O)(=O)C(F)(F)F
Solvent: Cc1ccccc1
Solvent: CC(Cl)(Cl)Cl
Solvent: CCOC(C)=O
Product: CCNC(=O)[C@H]1O[C@@H](n2cnc3c(Cl)nc(N)nc32)[C@H](OC(=O)c2ccccc2)[C@@H]1OC(=O)c1ccccc1
Temperature: 25 °C

Procedure:
A suspension of 2-amino-6-chloropurine (4.60 g, 27.13 mmol) in 1,1,1-trichloroethane (230 ml) was treated with N,O-bis(trimethylsilyl)acetamide (20 ml, 81.4 mmol). The mixture was heated under reflux for 6 hours. The solution was allowed to cool to room temperature and the solvent was removed under reduced pressure. The residue was treated with a solution of (2S,3S,4R,5R)-5-(acetyloxy)-4-(benzoyloxy)-2-[(ethylamino)carbonyl]tetrahydro-3-furanyl benzoate and (2S,3S,4R,5S)-5-(acetyloxy)-4-(benzoyloxy)-2-[(ethylamino)carbonyl]tetrahydro-3-furanyl benzoate (Preparation 18) (14.39 g, 32.6 mmol) in anhydrous toluene (230 ml) and trimethylsilyl trifluoromethanesulfonate (20 ml, 108.5 mmol). The resulting solution was then heated at 90° C. under a nitrogen atmosphere for 90 minutes. The mixture was cooled to room temperature, diluted with ethyl acetate (250 ml) and washed with a saturated aqueous solution of sodium hydrogen carbonate (350 ml) and then brine (350 ml). The organic layer was separated, dried over anhydrous magnesium sulphate, filtered and evaporated under reduced pressure. The residue was purified by column chromatography on silica gel eluting with dichloromethane:methanol (98:2 by volume) to afford the title compound as a foam (8.1 g).