Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: F[C:2]1[CH:7]=[C:6]([C:8]2[CH:9]=[N:10][NH:11][C:12]=2[CH:13]([CH3:15])[CH3:14])[CH:5]=[CH:4][N:3]=1.[CH3:16][C:17]1[CH:24]=[CH:23][CH:22]=[CH:21][C:18]=1[CH2:19][NH2:20]>CS(C)=O.CCOC(C)=O>[CH:13]([C:12]1[NH:11][N:10]=[CH:9][C:8]=1[C:6]1[CH:5]=[CH:4][N:3]=[C:2]([NH:20][CH2:19][C:18]2[CH:21]=[CH:22][CH:23]=[CH:24][C:17]=2[CH3:16])[CH:7]=1)([CH3:15])[CH3:14]
Reactant: CC(C)c1[nH]ncc1-c1ccnc(F)c1
Reactant: Cc1ccccc1CN
Solvent: CS(C)=O
Solvent: CCOC(C)=O
Product: Cc1ccccc1CNc1cc(-c2cn[nH]c2C(C)C)ccn1
Temperature: 150 °C
Reaction time: 8 h
Yield: 40.9 %

Procedure:
To a solution of 2-fluoro-4-(5-isopropyl-1H-pyrazol-4-yl)-pyridine (30 mg, 0.15 mmol) in anhydrous DMSO (0.25 mL) is added 2-methyl-benzylamine (37 uL, 0.3 mmol). The reaction mixture is stirred at 150° C. overnight, diluted with EtOAc, and washed with water and brine. The organic layer is dried over sodium sulfate and concentrated in vacuo. The crude product is purified by preparative HPLC to provide 18.8 mg of [4-(5-isopropyl-1H-pyrazol-4-yl)-pyridin-2-yl]-(2-methyl-benzyl)-amine. (Example 1)
Reaction SMILES: [O:1]1CCCC1.[CH3:6][O:7][C:8]1[C:13]([O:14][CH3:15])=[CH:12][C:11]([CH2:16][CH2:17][C:18]([N:20]2[CH2:25][CH2:24][N:23]([C:26]3[CH:31]=[CH:30][CH:29]=[CH:28][C:27]=3[O:32][CH3:33])[CH2:22][CH2:21]2)=O)=[C:10]([N:34]2[CH:38]=[CH:37][CH:36]=[CH:35]2)[CH:9]=1.O.[ClH:40]>C(O)C>[OH2:1].[ClH:40].[ClH:40].[CH3:6][O:7][C:8]1[C:13]([O:14][CH3:15])=[CH:12][C:11]([CH2:16][CH2:17][CH2:18][N:20]2[CH2:25][CH2:24][N:23]([C:26]3[CH:31]=[CH:30][CH:29]=[CH:28][C:27]=3[O:32][CH3:33])[CH2:22][CH2:21]2)=[C:10]([N:34]2[CH:38]=[CH:37][CH:36]=[CH:35]2)[CH:9]=1.[CH3:6][O:7][C:8]1[C:13]([O:14][CH3:15])=[CH:12][C:11]([CH2:16][CH2:17][CH2:18][N:20]2[CH2:25][CH2:24][N:23]([C:26]3[CH:31]=[CH:30][CH:29]=[CH:28][C:27]=3[O:32][CH3:33])[CH2:22][CH2:21]2)=[C:10]([N:34]2[CH:38]=[CH:37][CH:36]=[CH:35]2)[CH:9]=1.[ClH:40].[ClH:40]
Reactant: COc1cc(CCC(=O)N2CCN(c3ccccc3OC)CC2)c(-n2cccc2)cc1OC
Reactant: C1CCOC1
Agent: Cl
Solvent: O
Solvent: CCO
Product: COc1cc(CCCN2CCN(c3ccccc3OC)CC2)c(-n2cccc2)cc1OC
Temperature: 25 °C
Reaction time: 9 h

Procedure:
To 100 ml of tetrahydrofuran were added 18 ml of 1.0M borane-tetrahydrofuran complex and 1.14 g of 1-(3-(4,5-dimethoxy-2-(1-pyrrolyl)phenyl)-1-oxopropyl)-4-(2-methoxyphenyl)piperazine at room temperature, and the mixture was heated under reflux for 27 hours. Since it was found that the reaction had not completed, 10 ml of the borane-tetrahydrofuran complex was further added, and the refluxing was continued for additional 9 hours. After cooling to room temperature, 10 ml of water was added to the reaction mixture, and the solvent was removed under reduced pressure. To the residue was added 35 ml of 5% hydrochloric acid, followed by heating at 50° to 60° C. for 2 hours. The reaction mixture was dried over anhydrous sodium sulfate and the solvent was evaporated. The residue was purified by silica gel column chromatography (chloroform) to yield 780 mg of a pale yellow oily substance, which was dissolved in 15 ml of ethanol, 1.0 ml of concentrated hydrochloric acid was added thereto, and the solvent was removed under reduced pressure. Recrystallization of the residue from ethanol-ethyl ether yielded 500 mg of the title compound as a colorless prism crystal.
Reaction SMILES: [CH2:1]([N:8]1[CH:12]=[C:11](I)[CH:10]=[N:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[Cl:14][C:15]1[C:20](B(O)O)=[CH:19][CH:18]=[CH:17][N:16]=1.C(=O)(O)[O-].[Na+]>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>[CH2:1]([N:8]1[CH:12]=[C:11]([C:20]2[C:15]([Cl:14])=[N:16][CH:17]=[CH:18][CH:19]=2)[CH:10]=[N:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: OB(O)c1cccnc1Cl
Reactant: Ic1cnn(Cc2ccccc2)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: [Na+]
Product: Clc1ncccc1-c1cnn(Cc2ccccc2)c1
Temperature: 85 °C

Procedure:
1-Benzyl-4-iodo-1H-pyrazole (1.35 g, 4.77 mmol), 2-chloropyridin-3-ylboronic acid (1.50 g, 9.53 mmol), sodium bicarbonate (1.20 g, 14.3 mmol) and Pd(PPh3)4 (276 mg, 0.239 mmol) were combined in an argon-purged sealed tube. Dimethoxyethane (8 mL) and water (5 mL) were added and the mixture was heated to 85° C. for 16 hours. The reaction was cooled to rt, diluted with water and extracted into EtOAc. The separated organic layer was dried over anhydrous sodium sulfate, filtered and concentrated. This residue was purified by silica gel chromatography (50-75% EtOAc/hexanes) to yield 3-(1-benzyl-1H-pyrazol-4-yl)-2-chloropyridine as a light yellow oil after concentration. MS m/z=270 [M+1]+. Calc'd for C15H12FN3: 269.74.
Reaction SMILES: O=[O+][O-].O=O.O=[O+][O-].[C:9]1([CH:15]([O:22][C:23](=[O:55])[CH:24]([N:28]2[CH:31]([S:32][S:33][C:34]3[O:35][C:36]4[CH:42]=[CH:41][CH:40]=[CH:39][C:37]=4[N:38]=3)[CH:30]([NH:43][C:44](=[O:53])[CH2:45][O:46][C:47]3[CH:52]=[CH:51][CH:50]=[CH:49][CH:48]=3)[C:29]2=[O:54])[C:25](=C)[CH3:26])[C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1.C1(C)C=CC=CC=1.C(OCC)(=[O:65])C>C(OCC)(=O)C>[C:9]1([CH:15]([O:22][C:23](=[O:55])/[C:24](/[N:28]2[CH:31]([S:32][S:33][C:34]3[O:35][C:36]4[CH:42]=[CH:41][CH:40]=[CH:39][C:37]=4[N:38]=3)[CH:30]([NH:43][C:44](=[O:53])[CH2:45][O:46][C:47]3[CH:52]=[CH:51][CH:50]=[CH:49][CH:48]=3)[C:29]2=[O:54])=[C:25](\[OH:65])/[CH3:26])[C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)[CH:10]=[CH:11][CH:12]=[CH:13][CH:14]=1
Reactant: CCOC(C)=O
Reactant: C=C(C)C(C(=O)OC(c1ccccc1)c1ccccc1)N1C(=O)C(NC(=O)COc2ccccc2)C1SSc1nc2ccccc2o1
Agent: O=O
Agent: O=[O+][O-]
Solvent: Cc1ccccc1
Product: C/C(O)=C(/C(=O)OC(c1ccccc1)c1ccccc1)N1C(=O)C(NC(=O)COc2ccccc2)C1SSc1nc2ccccc2o1

Procedure:
(aix) Approximately one equivalent of ozone (in the form of an O2 /O3 mixture) is passed into a solution, cooled to -70° C., of 3.35 g of 2-[4-(benzoxazol-2-yldithio)-3-phenoxyacetamido-2-oxoazetidin-1-yl]-3-methylene-butyric acid diphenylmethyl ester in 125 ml of ethyl acetate, until starting material is no longer detectable by thin layer chromatography (silica gel; toluene/ethyl acetate, 3:1). The solution is concentrated by evaporation to about 50 ml in vacuo, mixed with 5 ml of dimethyl sulphide and stirred until the potassium iodide/starch test no longer gives a reaction. The mixture is concentrated by evaporation in vacuo, the residue is dissolved in 150 ml of benzene and the solution is washed with water. The organic phase is dried over sodium sulphate and concentrated by evaporation. The residue is chromatographed on 150 g of acid-washed silica gel, using toluene/ethyl acetate, 4:1. 2-[4-(Benzoxazol-2-yldithio)-3-phenoxyacetamido-2-oxoazetidin-1-yl]-3-hydroxy-crotonic acid diphenylmethyl ester is obtained in the form of a white foam; IR spectrum (methylene chloride): characteristic bands at 5.60, 5.90 and 6.0 μ.
Reaction SMILES: Br[C:2]1[C:3]([C:23]2[CH:28]=[CH:27][C:26]([Cl:29])=[CH:25][CH:24]=2)=[CH:4][C:5]2[N:6]([C:8]([CH2:11][C:12]3[C:13]([CH3:22])=[N:14][C:15]([C:18]([F:21])([F:20])[F:19])=[CH:16][CH:17]=3)=[N:9][N:10]=2)[CH:7]=1.[Cl:30][C:31]1[CH:36]=[C:35]([CH3:37])[CH:34]=[CH:33][C:32]=1B(O)O.C([O-])([O-])=O.[K+].[K+].ClC1C=CC(C2C(C3C=CC(Cl)=CC=3Cl)=CN3C(CC4C=NC(C(F)(F)F)=CC=4)=NN=C3C=2)=CC=1>O1CCOCC1.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>[Cl:29][C:26]1[CH:27]=[CH:28][C:23]([C:3]2[C:2]([C:32]3[CH:33]=[CH:34][C:35]([CH3:37])=[CH:36][C:31]=3[Cl:30])=[CH:7][N:6]3[C:8]([CH2:11][C:12]4[C:13]([CH3:22])=[N:14][C:15]([C:18]([F:20])([F:19])[F:21])=[CH:16][CH:17]=4)=[N:9][N:10]=[C:5]3[CH:4]=2)=[CH:24][CH:25]=1
Reactant: Cc1ccc(B(O)O)c(Cl)c1
Reactant: Cc1nc(C(F)(F)F)ccc1Cc1nnc2cc(-c3ccc(Cl)cc3)c(Br)cn12
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: FC(F)(F)c1ccc(Cc2nnc3cc(-c4ccc(Cl)cc4)c(-c4ccc(Cl)cc4Cl)cn23)cn1
Agent: O=C([O-])[O-]
Solvent: C1COCCO1
Product: Cc1ccc(-c2cn3c(Cc4ccc(C(F)(F)F)nc4C)nnc3cc2-c2ccc(Cl)cc2)c(Cl)c1
Yield: 61.6 %

Procedure:
The title compound (6.5 mg, 60%) as a white powder was prepared from 6-bromo-7-(4-chlorophenyl)-3-((2-methyl-6-(trifluoromethyl)pyridin-3-yl)methyl)-[1,2,4]triazolo[4,3-a]pyridine (9.5 mg, 0.020 mmol), 2-chloro-4-methylphenylboronic acid (6.7 mg, 0.039 mmol), K2CO3 (8.2 mg, 0.059 mmol) and Pd(PPh3)4 (2.8 mg, 0.002 mmol) in 1,4-dioxane (0.28 mL) and 1H2O (0.09 mL) by the procedures analogous to those described for 7-(4-chlorophenyl)-6-(2,4-dichlorophenyl)-3-((6-(trifluoromethyl)pyridin-3-yl)methyl)-[1,2,4]triazolo[4,3-a]pyridine (Example 56E). LC/MS (method B): retention time 2.01 min, [M+H]+=527.3.
Reaction SMILES: [F:1][C:2]([F:19])([F:18])[C:3]([N:5]1[CH2:10][CH2:9][N:8]([C:11]2[CH:17]=[CH:16][C:14]([NH2:15])=[CH:13][CH:12]=2)[CH2:7][CH2:6]1)=[O:4].CCN(CC)CC.C1C=CC2N(O)N=NC=2C=1.[C:37]([O:41][C:42]([N:44]1[CH2:49][CH2:48][CH:47]([C:50](O)=[O:51])[CH2:46][CH2:45]1)=[O:43])([CH3:40])([CH3:39])[CH3:38].C(Cl)CCl>CN(C=O)C>[F:19][C:2]([F:1])([F:18])[C:3]([N:5]1[CH2:6][CH2:7][N:8]([C:11]2[CH:17]=[CH:16][C:14]([NH:15][C:50]([CH:47]3[CH2:48][CH2:49][N:44]([C:42]([O:41][C:37]([CH3:40])([CH3:39])[CH3:38])=[O:43])[CH2:45][CH2:46]3)=[O:51])=[CH:13][CH:12]=2)[CH2:9][CH2:10]1)=[O:4]
Reactant: Nc1ccc(N2CCN(C(=O)C(F)(F)F)CC2)cc1
Reactant: CC(C)(C)OC(=O)N1CCC(C(=O)O)CC1
Agent: On1nnc2ccccc21
Solvent: CN(C)C=O
Solvent: ClCCCl
Solvent: CCN(CC)CC
Product: CC(C)(C)OC(=O)N1CCC(C(=O)Nc2ccc(N3CCN(C(=O)C(F)(F)F)CC3)cc2)CC1
Temperature: 25 °C
Reaction time: 18 h

Procedure:
A mixture of 4-(1-N-trifluoroacetyl-4-piperazinyl)aniline (3.0 g, 9.9 mmol), Et3N (2.2 mL, 19 mmol), HOBt (1.5 g, 9.9 mmol), 1-t-butyloxycarbonyl-4-carboxypiperidine (2.3 g, 9.9 mmol) and EDC (1.9 g, 9.9 mmol) in DMF (15 mL) was stirred at RT for 18 hr. Solution was concentrated and the residue was dissolved in EtOAc. EtOAc was washed with: H2O, 5% citric acid (2×), water, 5% NaHCO3 (2×), water and brine. EtOAc was concentrated to givethe title compound (4.35 g, 91%). MS (ES) m/e 485 [M+H]+.
Reaction SMILES: [C:1]([O:4][C@:5]1([C@:25]2([CH3:26])[C@H:11]([C@H:12]3[C@H:22]([C@@H:23]([F:27])[CH2:24]2)[C@:20]2([CH3:21])[C:15](=[CH:16][C:17](=[O:28])[CH2:18][CH2:19]2)[CH2:14][CH2:13]3)[CH2:10][CH2:9]1)[C:6](=[O:8])[CH3:7])(=[O:3])[CH3:2].C(Cl)CCl.C1(Cl)C(=O)C(Cl)=C(Cl)C(=O)C=1Cl.C1(C)C=CC(S(O)(=O)=O)=CC=1>C(O)(C)(C)C>[C:1]([O:4][C@:5]1([C@:25]2([CH3:26])[C@H:11]([C@H:12]3[C@H:22]([C@@H:23]([F:27])[CH2:24]2)[C@:20]2([CH3:21])[C:15](=[CH:16][C:17](=[O:28])[CH2:18][CH2:19]2)[CH:14]=[CH:13]3)[CH2:10][CH2:9]1)[C:6](=[O:8])[CH3:7])(=[O:3])[CH3:2]
Reactant: CC(=O)O[C@]1(C(C)=O)CC[C@H]2[C@@H]3CCC4=CC(=O)CC[C@]4(C)[C@H]3[C@@H](F)C[C@@]21C
Agent: Cc1ccc(S(=O)(=O)O)cc1
Agent: O=C1C(Cl)=C(Cl)C(=O)C(Cl)=C1Cl
Solvent: CC(C)(C)O
Solvent: ClCCCl
Product: CC(=O)O[C@]1(C(C)=O)CC[C@H]2[C@@H]3C=CC4=CC(=O)CC[C@]4(C)[C@H]3[C@@H](F)C[C@@]21C

Procedure:
One gram of 17-acetoxy-11β-fluoro-4-pregnene-3,20-dione is combined in a solvent mixture of 6 ml. of ethylene chloride and 10 ml. of tert.-butanol with 1.5 g. of chloranil and 10 mg. of p-toluenesulfonic acid. The mixture is heated for 6 hours under reflux. Then, the mixture is filtered off from the chloranil and the precipitate washed with ethyl acetate and ether. The filtrate is diluted with ether and combined repeatedly with 2N NaOH solution. The solution is then washed neutral with water and dried. After chromatography of the crude product on silica gel with 14- 17% acetone/hexane, 344 mg. of 17-acetoxy-11β-fluoro-4,6-pregnadiene-3,20-dione is obtained; m.p. 220°-222° C. from acetone/hexane. UV: ε280 = 26,500.
Reaction SMILES: F[C:2]1[CH:7]=[CH:6][C:5]([N+:8]([O-:10])=[O:9])=[C:4]([O:11][CH3:12])[CH:3]=1.[NH2:13][CH2:14][CH2:15][CH2:16][N:17]1[CH2:21][CH2:20][CH2:19][CH2:18]1.C(N(C(C)C)CC)(C)C>O1CCOCC1>[CH3:12][O:11][C:4]1[CH:3]=[C:2]([NH:13][CH2:14][CH2:15][CH2:16][N:17]2[CH2:21][CH2:20][CH2:19][CH2:18]2)[CH:7]=[CH:6][C:5]=1[N+:8]([O-:10])=[O:9]
Reactant: NCCCN1CCCC1
Reactant: COc1cc(F)ccc1[N+](=O)[O-]
Solvent: C1COCCO1
Solvent: CCN(C(C)C)C(C)C
Product: COc1cc(NCCCN2CCCC2)ccc1[N+](=O)[O-]
Temperature: 95 °C
Reaction time: 24 h

Procedure:
1 g (5.884 mmol) 4-fluoro-2-methoxy-1-nitro-benzene, 975 mg (7.369 mmol) 1-(3-aminopropyl)pyrrolidine and 1.5 ml (8.765 mmol) diisopropyethylamine are dissolved in 5 ml dioxane and stirred for 24 h at 95° C. The solvents are eliminated in vacuo and the crude product is purified by column chromatography. The carrier used is silica gel and the eluant used is dichloromethane, to which 15% of a mixture of 90% methanol and 10% saturated aqueous ammonia solution has been added.
Reaction SMILES: [O:1]=[C:2]1[CH2:10][C:9]2[C:4](=[C:5]([O:12][C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=3[Cl:19])[CH:6]=[C:7]([Cl:11])[CH:8]=2)[NH:3]1.[OH-].[Na+].[O:22]1CCOCC1>O>[NH2:3][C:4]1[C:5]([O:12][C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=2[Cl:19])=[CH:6][C:7]([Cl:11])=[CH:8][C:9]=1[CH2:10][C:2]([OH:22])=[O:1]
Reactant: O=C1Cc2cc(Cl)cc(Oc3ccccc3Cl)c2N1
Reactant: C1COCCO1
Agent: [Na+]
Agent: [OH-]
Solvent: O
Product: Nc1c(CC(=O)O)cc(Cl)cc1Oc1ccccc1Cl

Procedure:
A mixture of 2-oxo-5-chloro-7-(2-chlorophenoxy)indoline (2.0 g.), sodium hydroxide (0.50 g.), dioxane (20 ml.) and water (30 ml.) was refluxed under heating for 23 hours. The reaction mixture was evaporated under reduced pressure and the residue was dissolved in water and filtered. The filtrate was washed with diethyl ether, and diethyl ether was added to the aqueous layer and adjusted to pH 5 with 1N-sulfuric acid. The diethyl ether layer was separated, washed with water, dried over magnesium sulfate and then evaporated. The residue was recrystallized from ethanol to give crystals of 2-[2-amino-3-(2-chlorophenoxy)-5-chlorophenyl]acetic acid (0.725 g.).
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[CH:4][C:5]([OH:25])=[C:6]([C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][C:9]=2[C:14]2[N:19]=[C:18]([C:20]([O:22][CH2:23][CH3:24])=[O:21])[CH:17]=[CH:16][CH:15]=2)[CH:7]=1.C(=O)([O-])[O-].[K+].[K+].[F:32][C:33]1[CH:40]=[CH:39][C:36]([CH2:37]Br)=[CH:35][CH:34]=1>CC(C)=O>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([O:25][CH2:37][C:36]2[CH:39]=[CH:40][C:33]([F:32])=[CH:34][CH:35]=2)=[C:6]([C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][C:9]=2[C:14]2[N:19]=[C:18]([C:20]([O:22][CH2:23][CH3:24])=[O:21])[CH:17]=[CH:16][CH:15]=2)[CH:7]=1
Reactant: CCOC(=O)c1cccc(-c2ccccc2-c2cc(Cl)ccc2O)n1
Reactant: Fc1ccc(CBr)cc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC(C)=O
Product: CCOC(=O)c1cccc(-c2ccccc2-c2cc(Cl)ccc2OCc2ccc(F)cc2)n1
Yield: 82.3 %

Procedure:
A mixture of ethyl 6-(5′-chloro-2′-hydroxy-2-biphenylyl)-2-pyridinecarboxylate (177 mg, 0.5 mmol), potassium carbonate (138 mg, 1 mmol) and 4-fluorobenzyl bromide (104 mg, 0.55 mmol) in acetone (4 ml) was stirred and refluxed for 2 hours then cooled, filtered, evaporated and chromatographed on silica eluting with ethyl acetate/iso-hexane (1:9) to give 190 mg of white solid. LC/MS t=3.79, [MH+] 462.3
Reaction SMILES: [N:1]1([CH2:7][CH2:8][CH2:9][C:10]([C:12]2[CH:24]=[CH:23][C:22]3[C:21]4[C:16](=[CH:17][C:18]([C:25](=[O:35])[CH2:26][CH2:27][CH2:28][N:29]5[CH2:34][CH2:33][CH2:32][CH2:31][CH2:30]5)=[CH:19][CH:20]=4)[CH2:15][C:14]=3[CH:13]=2)=[O:11])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[BH4-].[Na+].O>CO>[N:1]1([CH2:7][CH2:8][CH2:9][CH:10]([C:12]2[CH:24]=[CH:23][C:22]3[C:21]4[C:16](=[CH:17][C:18]([CH:25]([CH2:26][CH2:27][CH2:28][N:29]5[CH2:30][CH2:31][CH2:32][CH2:33][CH2:34]5)[OH:35])=[CH:19][CH:20]=4)[CH2:15][C:14]=3[CH:13]=2)[OH:11])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6]1
Reactant: O=C(CCCN1CCCCC1)c1ccc2c(c1)Cc1cc(C(=O)CCCN3CCCCC3)ccc1-2
Agent: [BH4-]
Agent: [Na+]
Solvent: CO
Solvent: O
Product: OC(CCCN1CCCCC1)c1ccc2c(c1)Cc1cc(C(O)CCCN3CCCCC3)ccc1-2
Temperature: -10 °C
Reaction time: 16 h

Procedure:
A solution of 24.5 g (0.052 mole) of 2,7-bis(4-piperidinobutyryl)fluorene dissolved in 400 ml of methanol is cooled to -10°C. and 3.8 g (0.1 mole) of sodium borohydride is slowly added wih stirring. The reaction mixture is gradually permitted to come to room temperature and stirring continued for an additional 16 hours. The contents of the reaction mixture are poured into approximately 1 liter of water, and the resulting solid which forms is filtered, washed with water and recrystallized from a solution of benzene. Recrystallization from a benzene-ether mixture results in the preparation of α, α'-bis(3-piperidinopropyl)-2,7-fluorenedimethanol having a m.p. of 181.5°-4.0°C, λmaxEtOH 273, and E 1cm1% 592.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[CH:4][C:5]([C:34]#[N:35])=[C:6]([C:8]2[C:13]([O:14][CH3:15])=[CH:12][N:11]([CH:16]([CH2:24][C@H:25]3[CH2:30][CH2:29][C@H:28]([O:31][CH3:32])[CH2:27][CH2:26]3)[C:17]([O:19]C(C)(C)C)=[O:18])[C:10](=[O:33])[CH:9]=2)[CH:7]=1.C(O)(C(F)(F)F)=O>ClCCl>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([C:34]#[N:35])=[C:6]([C:8]2[C:13]([O:14][CH3:15])=[CH:12][N:11]([CH:16]([CH2:24][C@H:25]3[CH2:30][CH2:29][C@H:28]([O:31][CH3:32])[CH2:27][CH2:26]3)[C:17]([OH:19])=[O:18])[C:10](=[O:33])[CH:9]=2)[CH:7]=1
Reactant: COc1cn(C(C[C@H]2CC[C@H](OC)CC2)C(=O)OC(C)(C)C)c(=O)cc1-c1cc(Cl)ccc1C#N
Solvent: O=C(O)C(F)(F)F
Solvent: ClCCl
Product: COc1cn(C(C[C@H]2CC[C@H](OC)CC2)C(=O)O)c(=O)cc1-c1cc(Cl)ccc1C#N

Procedure:
1.70 g (purity 87%, 3.39 mmol) of tert-butyl 2-[4-(5-chloro-2-cyanophenyl)-5-methoxy-2-oxopyridin-1(2H)-yl]-3-(trans-4-methoxycyclohexyl)propanoate (racemate) in 6 ml of dichloromethane and 5.04 ml (67.9 mmol) of TFA were reacted according to General Method 6A. Yield: 1.70 g (quant.)
Reaction SMILES: [CH3:1][N:2]([C@H:36]([CH3:41])[C:37]([O:39][CH3:40])=[O:38])[C:3](=[O:35])[CH:4]([C:13]1[CH:18]=[CH:17][C:16]([O:19][CH2:20][C:21]2[CH:26]=[C:25]([C:27]([F:30])([F:29])[F:28])[CH:24]=[C:23]([C:31]([F:34])([F:33])[F:32])[CH:22]=2)=[CH:15][CH:14]=1)[CH2:5][C:6]([O:8]C(C)(C)C)=[O:7].C(O)(C(F)(F)F)=O>C(Cl)Cl>[CH3:1][N:2]([C@H:36]([CH3:41])[C:37]([O:39][CH3:40])=[O:38])[C:3](=[O:35])[CH:4]([C:13]1[CH:14]=[CH:15][C:16]([O:19][CH2:20][C:21]2[CH:22]=[C:23]([C:31]([F:33])([F:34])[F:32])[CH:24]=[C:25]([C:27]([F:28])([F:29])[F:30])[CH:26]=2)=[CH:17][CH:18]=1)[CH2:5][C:6]([OH:8])=[O:7]
Reactant: COC(=O)[C@@H](C)N(C)C(=O)C(CC(=O)OC(C)(C)C)c1ccc(OCc2cc(C(F)(F)F)cc(C(F)(F)F)c2)cc1
Solvent: ClCCl
Solvent: O=C(O)C(F)(F)F
Product: COC(=O)[C@@H](C)N(C)C(=O)C(CC(=O)O)c1ccc(OCc2cc(C(F)(F)F)cc(C(F)(F)F)c2)cc1
Yield: 110.4 %

Procedure:
Methyl 2-{N-methyl-N-[(R/S)-α-t-butoxycarbonylmethyl-4-(3,5-bistrifluoromethylbenzyloxy)phenylacetyl]amino}-(R)-propionate 48e (1.46 g, 2.47 mmol) was treated with 50% TFA in CH2Cl2 (20 mL) for 1 hour and the solution was concentrated in vacuo to give the acid (1.46 g, 100%) as a syrup. MS (ESI): (M+H)+=535.9.
Reaction SMILES: [OH:1][C:2]1[C:11]2[CH:12]=[CH:13][CH:14]=[CH:15][C:10]=2[C:9]2[N:8]=[CH:7][CH:6]=[C:5]3[CH2:16][CH2:17][CH2:18][C:3]=1[C:4]=23>C(O)(=O)C.[Pt]>[OH:1][C:2]1[C:11]2[CH2:12][CH2:13][CH2:14][CH2:15][C:10]=2[C:9]2[N:8]=[CH:7][CH:6]=[C:5]3[CH2:16][CH2:17][CH2:18][C:3]=1[C:4]=23
Reactant: Oc1c2c3c(ccnc3c3ccccc13)CCC2
Agent: [Pt]
Solvent: CC(=O)O
Product: Oc1c2c(c3nccc4c3c1CCC4)CCCC2
Temperature: 65 °C
Yield: 86.9 %

Procedure:
7-Hydroxy-5,6-dihydro-4H-dibenzo[de,h]quinoline (16.4 g) and Adams platinum (2.78 g) suspended in acetic acid (400 cc) are placed under an initial hydrogen pressure of 25 bars at 25° C. The mixture is stirred and heated at 65° C. for 24 hours. After cooling to 25° C., the catalyst is filtered off and washed three times with acetic acid (total 200 cc). The combined organic filtrates are evaporated to dryness. The residue is taken up in water (500 cc) and the mixture is neutralised by the addition of a 10% (w/v) aqueous sodium bicarbonate solution (50 cc). The precipitate is filtered off, washed three times with distilled water (total 600 cc) and dried under reduced pressure. The crystalline product thus obtained (17 g) is combined with a portion (7.4 g) of product prepared in the same way, the whole is recrystallised from butyl acetate (550 cc). After cooling for 48 hours at about 5° C., the resulting crystals are filtered off, washed twice with diethyl ether (total 75 cc) and dried under reduced pressure (1 mm Hg) at 100° C. The product obtained (18.5 g) is recrystallised a second time from propanol (360 cc). After cooling for 48 hours at about 5° C., the crystals are filtered off, washed twice with diethyl ether (total 75 cc) and dried under reduced pressure (1 mm Hg) at 100° C. for 4 hours. 7-Hydroxy-5,6,8,9,10,11-hexahydro-4H-dibenzo[de,h]-quinoline (14.5 g), melting at 224° C., is thus obtained.
Reaction SMILES: I[C:2]1[N:3]=[C:4]([NH2:20])[C:5]2[N:6]=[CH:7][N:8]([C:18]=2[N:19]=1)[C@@H:9]1[O:17][C@H:14]([CH2:15][OH:16])[C@@H:12]([OH:13])[C@H:10]1[OH:11].[F:21][C:22]([F:37])([F:36])[C:23]1[CH:24]=[C:25](B(O)O)[CH:26]=[C:27]([C:29]([F:32])([F:31])[F:30])[CH:28]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>C1(C)C=CC=CC=1.C(O)C.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[NH2:20][C:4]1[N:3]=[C:2]([C:25]2[CH:26]=[C:27]([C:29]([F:32])([F:30])[F:31])[CH:28]=[C:23]([C:22]([F:21])([F:37])[F:36])[CH:24]=2)[N:19]=[C:18]2[C:5]=1[N:6]=[CH:7][N:8]2[C@H:9]1[C@H:10]([OH:11])[C@H:12]([OH:13])[C@@H:14]([CH2:15][OH:16])[O:17]1
Reactant: Nc1nc(I)nc2c1ncn2[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O
Reactant: OB(O)c1cc(C(F)(F)F)cc(C(F)(F)F)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: [Cs+]
Solvent: CCO
Solvent: Cc1ccccc1
Product: Nc1nc(-c2cc(C(F)(F)F)cc(C(F)(F)F)c2)nc2c1ncn2[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O
Yield: 30 %

Procedure:
A solution of 2-iodo adenosine (1.00 g, 2.53 mmol), 3,5-bis(trifluoromethyl)phenylboronic acid (784 mg, 3.04 mmol), cesium carbonate (1.81 g, 6.08 mmol) and Pd(PPh3)4 (293 mg, 0.25 mmol) in toluene (2.4 mL) and ethanol (4.8 mL) was heated in a Biotage microwave (120° C., absorption high, pre-stirring 30 s) for 40 min in 2 batches and the crude reaction mixtures were combined. The solvents were then removed in vacuo and the residue dissolved in EtOAc (200 mL) and washed with sat. aq. NaHCO3 (100 mL) and brine (100 mL). Purification by flash column chromatography (normal phase, ICN silica, 50 g, 18-32μ, gradient 5-25% ethanol in DCM, residue dry loaded, product eluted in 25% ethanol) afforded (2R,3R,4S,5R)-2-{6-amino-2-[3,5-bis(trifluoromethyl)phenyl]-9H-purin-9-yl}-5-(hydroxymethyl)tetrahydrofuran-3,4-diol 11 as an off-white glass (364 mg, 30%).
Reaction SMILES: Br[CH:2]1[CH2:7][CH2:6][CH2:5][CH:4]=[CH:3]1.[C:8]1(=[O:18])[NH:12][C:11](=[O:13])[C:10]2=[CH:14][CH:15]=[CH:16][CH:17]=[C:9]12.[K]>CN(C=O)C.O>[CH:2]1([N:12]2[C:8](=[O:18])[C:9]3[C:10](=[CH:14][CH:15]=[CH:16][CH:17]=3)[C:11]2=[O:13])[CH2:7][CH2:6][CH2:5][CH:4]=[CH:3]1
Reactant: BrC1C=CCCC1
Reactant: O=C1NC(=O)c2ccccc21
Agent: [K]
Solvent: O
Solvent: CN(C)C=O
Product: O=C1c2ccccc2C(=O)N1C1C=CCCC1
Temperature: 25 °C
Reaction time: 30 h
Yield: 73717.9 %

Procedure:
To a solution of 3-bromo-cyclohexene (500 g, 3.12 mmol) in DMF (2000 mL) was added potassium phtalimide (580 g, 3.12 mmol), and the reaction mixture was stirred at room temperature for 30 h. The reaction mixture was diluted with water (1000 mL), extracted with ethyl acetate (3 times), and the combined organic layers were concentrated to give 2-cyclohex-2-enyl-isoindole-1,3-dione (520 g, 2.30 mol) as a gray solid.