Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][C:2]1([CH3:13])[C@H:7]2[C@@H:3]1[C@H:4]([C:9](Br)([Br:11])[Br:10])[O:5][C:6]2=[O:8].CC1(C)[C@H]2[C@@H]1[C@@H](C(Br)(Br)Br)OC2=O.C(=O)([O-])O.[Na+].[H][H].Cl.C(OC)(C)(C)C>CO>[Br:10][C:9]([Br:11])=[CH:4][C@H:3]1[C@@H:7]([C:6]([OH:8])=[O:5])[C:2]1([CH3:1])[CH3:13]
Reactant: CC1(C)[C@H]2[C@H](C(Br)(Br)Br)OC(=O)[C@H]21
Reactant: [H][H]
Agent: CC1(C)[C@@H]2[C@H]1C(=O)O[C@@H]2C(Br)(Br)Br
Agent: Cl
Agent: O=C([O-])O
Solvent: CO
Solvent: COC(C)(C)C
Product: CC1(C)[C@H](C(=O)O)[C@@H]1C=C(Br)Br
Reaction time: 1 h

Procedure:
A mixture of (1R,4R,5S)-6,6-dimethyl-4-(tribromomethyl)-3-oxabicyclo [3.1.0]hexan-2-one (I, R1=X1=X2=Br) and (1R,4S,5S)-6,6-dimethyl-4-(tribromomethyl)-3-oxabicyclo[3.1.0]hexan-2-one (I, R1X1=X2=Br), 0.75 g (0.002 mol), is stirred with sodium hydrogen carbonate, 0.421 g (0.005 mol), and-Pt(C) 5%, 0.06 g in about 9 ml of methanol at 50° C. with gaseous hydrogen being supplied below the liquid surface. Samples taken out for GC analysis are treated with aqueous hydrochloric acid/methyl t-butyl ether and analysed on GC. Already after 1 hour GC analysis (area-%) shows a content of 42% of II and 34% of unreacted I. Identification of II is effected as shown in Example 1.
Reaction SMILES: Cl[C:2]1[C:11]2[C:6](=[CH:7][C:8]([NH:14][C:15](=[O:17])[CH3:16])=[C:9]([O:12][CH3:13])[CH:10]=2)[N:5]=[CH:4][C:3]=1[C:18]#[N:19].[Cl:20][C:21]1[CH:27]=[C:26]([Cl:28])[C:25]([O:29][CH3:30])=[CH:24][C:22]=1[NH2:23].Cl.N1C=CC=CC=1>C(OCCO)C>[C:18]([C:3]1[CH:4]=[N:5][C:6]2[C:11]([C:2]=1[NH:23][C:22]1[CH:24]=[C:25]([O:29][CH3:30])[C:26]([Cl:28])=[CH:27][C:21]=1[Cl:20])=[CH:10][C:9]([O:12][CH3:13])=[C:8]([NH:14][C:15](=[O:17])[CH3:16])[CH:7]=2)#[N:19]
Reactant: COc1cc(N)c(Cl)cc1Cl
Reactant: COc1cc2c(Cl)c(C#N)cnc2cc1NC(C)=O
Agent: Cl
Solvent: c1ccncc1
Solvent: CCOCCO
Product: COc1cc(Nc2c(C#N)cnc3cc(NC(C)=O)c(OC)cc23)c(Cl)cc1Cl
Temperature: 135 °C
Yield: 70.9 %

Procedure:
An amount of 9.7 g (0.035 mol) of N-(4-chloro-3-cyano-6-methoxy-7-quinolinyl)acetamide was stirred in 97 ml of 2-ethoxyethanol. To this were added 2,4-dichloro-5-methoxyaniline (7.4 g, 0.038 mol), and 4.1 g (0.035 mol) pyridine hydrochloride, and the mixture was heated at 135° C. for 3 hours. The solvent was evaporated and the solid was stirred in saturated sodium bicarbonate solution and extracted with ethyl acetate. The organic phase was washed with saturated brine solution, dried over sodium sulfate and evaporated to dryness to give a brown solid (10.7 g, 71% yield), mp 267-270° C.; 1H NMR (DMSO-d6) δ 9.94 (s, 1H), 9.01 (s, 1H), 8.99 (s, 1H), 8.42 (s, 1H), 7.97 (m, 1H), 7.86 (s, 1H), 7.53 (m, 1H), 4.12 (s, 3H), 3.88 (s, 3H), 2.27 (s, 3H); MS (ES) m/z 431.1 (M+1). Analysis for C20H16Cl2N4O3.7H2O: Found: C, 43.23; H, 3.35; N, 10.24. Calcd: C, 43.06; H, 5.38; N, 10.05.
Reaction SMILES: [CH2:1]([NH:8][CH:9]1[CH2:14][CH2:13][N:12]([C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[CH2:11][CH2:10]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CCN(CC)CC.[C:29](Cl)(=[O:31])[CH3:30]>C(Cl)Cl>[CH2:1]([N:8]([CH:9]1[CH2:14][CH2:13][N:12]([C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[CH2:11][CH2:10]1)[C:29](=[O:31])[CH3:30])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: CC(=O)Cl
Reactant: CC(C)(C)OC(=O)N1CCC(NCc2ccccc2)CC1
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: CC(=O)N(Cc1ccccc1)C1CCN(C(=O)OC(C)(C)C)CC1
Temperature: 25 °C
Reaction time: 8 h
Yield: 99.9 %

Procedure:
To a solution of tert-butyl 4-(benzylamino)piperidine-1-carboxylate (8.1 g, 28.0 mmol) and Et3N (7.8 mL, 56.0 mmol) in CH2Cl2 (100 mL) was added acetyl chloride (2.4 mL, 33.5 mmol) and the reaction was stirred at room temperature overnight, then concentrated in vacuo. Purification by flash chromatography on silica gel, eluting with 30% to 60% EtOAc/CH2Cl2, afforded tert-butyl 4-(N-benzylacetamido)piperidine-1-carboxylate (9.3 g, 99%).
Reaction SMILES: OC1(C2C=CC=CC=2)CCN(C2N=C[C:11]([NH:14][C:15]([C:17]3[O:21][C:20]([N:22]4[CH2:27][CH2:26][CH2:25][CH2:24][CH2:23]4)=[N:19][C:18]=3[C:28]([F:31])([F:30])[F:29])=[O:16])=[CH:10][CH:9]=2)CC1.NC1[CH:40]=[C:41]2[C:46](=CC=1)[CH2:45][N:44]([C:49]([O:51][C:52]([CH3:55])([CH3:54])[CH3:53])=[O:50])[CH2:43][CH2:42]2>>[N:22]1([C:20]2[O:21][C:17]([C:15]([NH:14][C:11]3[CH:40]=[C:41]4[C:42](=[CH:9][CH:10]=3)[CH2:43][N:44]([C:49]([O:51][C:52]([CH3:55])([CH3:54])[CH3:53])=[O:50])[CH2:45][CH2:46]4)=[O:16])=[C:18]([C:28]([F:31])([F:30])[F:29])[N:19]=2)[CH2:27][CH2:26][CH2:25][CH2:24][CH2:23]1
Reactant: CC(C)(C)OC(=O)N1CCc2cc(N)ccc2C1
Reactant: O=C(Nc1ccc(N2CCC(O)(c3ccccc3)CC2)nc1)c1oc(N2CCCCC2)nc1C(F)(F)F
Product: CC(C)(C)OC(=O)N1CCc2cc(NC(=O)c3oc(N4CCCCC4)nc3C(F)(F)F)ccc2C1

Procedure:
Compound 153 was prepared by the general procedure for compound 1, by using compound A-4 and tert-butyl 6-amino-3,4-dihydroisoquinoline-2(1H)-carboxylate as the starting materials. 1H NMR (400 MHz, DMSO-d6) δ 10.06 (s, 1H), 7.54 (s, 1H), 7.47 (d, 1H, J=8.4 Hz), 7.15 (d, 1H, J=8.4 Hz), 4.47 (s, 2H), 3.61 (m, 4H), 3.55 (t, 2H, J=5.9 Hz), 2.77 (t, 2H, J=5.9 Hz), 1.61 (m, 6H), 1.43 (s, 9H); LCMS (ESI) Rt=5.47 min, [M+1]+ 495.3.
Reaction SMILES: [Cl:1][C:2]1[C:7]([OH:8])=[CH:6][C:5]([N:9]2[C:13](=[O:14])[C:12]3[CH2:15][CH2:16][CH2:17][CH2:18][C:11]=3[C:10]2=[O:19])=[C:4]([F:20])[CH:3]=1.C(=O)([O-])[O-].[K+].[K+].Cl[CH2:28][C:29]([O:31][CH2:32][CH2:33][CH2:34][CH2:35][CH3:36])=[O:30].O>CN(C)C=O>[Cl:1][C:2]1[C:7]([O:8][CH2:28][C:29]([O:31][CH2:32][CH2:33][CH2:34][CH2:35][CH3:36])=[O:30])=[CH:6][C:5]([N:9]2[C:10](=[O:19])[C:11]3[CH2:18][CH2:17][CH2:16][CH2:15][C:12]=3[C:13]2=[O:14])=[C:4]([F:20])[CH:3]=1
Reactant: CCCCCOC(=O)CCl
Reactant: O=C1C2=C(CCCC2)C(=O)N1c1cc(O)c(Cl)cc1F
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: O
Product: CCCCCOC(=O)COc1cc(N2C(=O)C3=C(CCCC3)C2=O)c(F)cc1Cl
Temperature: 25 °C
Yield: 41.9 %

Procedure:
To a solution of N-(4-chloro-2-fluoro-5-hydroxyphenyl)-3,4,5,6-tetrahydrophthalimide (3 g) in dimethylformamide (100 ml), anhydrous potassium carbonate (0.8 g) and then amyl chloroacetate (1.9 g) were added, and the resultant mixture was heated at 70° to 80° C. for 3 hours. The reaction mixture was cooled to room temperature, admixed with water and extracted with diethyl ether. The etheral layer was washed with water, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography to give the compound (I) (1.8 g).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:27]=[C:26]([O:28][CH3:29])[CH:25]=[CH:24][C:4]=1[CH2:5][N:6]([C:19]1[S:23][N:22]=[CH:21][N:20]=1)[S:7]([C:10]1[CH:15]=[C:14]([F:16])[C:13](F)=[CH:12][C:11]=1[F:18])(=[O:9])=[O:8].[CH3:30][N:31]1[C:35]([C@H:36]2[CH2:41][CH2:40][CH2:39][CH2:38][C@@H:37]2[OH:42])=[CH:34][CH:33]=[N:32]1.[H-].[Na+]>CS(C)=O>[CH3:1][O:2][C:3]1[CH:27]=[C:26]([O:28][CH3:29])[CH:25]=[CH:24][C:4]=1[CH2:5][N:6]([C:19]1[S:23][N:22]=[CH:21][N:20]=1)[S:7]([C:10]1[CH:15]=[C:14]([F:16])[C:13]([O:42][C@H:37]2[CH2:38][CH2:39][CH2:40][CH2:41][C@@H:36]2[C:35]2[N:31]([CH3:30])[N:32]=[CH:33][CH:34]=2)=[CH:12][C:11]=1[F:18])(=[O:9])=[O:8]
Reactant: Cn1nccc1[C@H]1CCCC[C@@H]1O
Reactant: COc1ccc(CN(c2ncns2)S(=O)(=O)c2cc(F)c(F)cc2F)c(OC)c1
Agent: [H-]
Agent: [Na+]
Solvent: CS(C)=O
Product: COc1ccc(CN(c2ncns2)S(=O)(=O)c2cc(F)c(O[C@H]3CCCC[C@@H]3c3ccnn3C)cc2F)c(OC)c1
Yield: 42.2 %

Procedure:
The reaction and aftertreatment were conducted in the same manner as in Example 1a by using the N-(2,4-dimethoxybenzyl)-2,4,5-trifluoro-N-(1,2,4-thiadiazol-5-yl)benzenesulfonamide (WO 2010/079443; 600 mg, 1.35 mmol), (1S*,2R*)-2-(1-methyl-1H-pyrazol-5-yl)cyclohexanol (240 mg, 1.33 mmol) prepared in Example 4a, sodium hydride (63%; 100 mg, 2.63 mmol) and DMSO (6.0 mL), to yield the title compound (340 mg, 42%) as a colorless solid.
Reaction SMILES: C(OC)(=O)[C:2]1[CH:11]=[CH:10][C:5]([C:6]([O:8][CH3:9])=[O:7])=[CH:4][CH:3]=1>[Pd]>[C:5]1([C:6]([O:8][CH3:9])=[O:7])([C:6]([O:8][CH3:9])=[O:7])[CH2:4][CH2:3][CH2:2][CH2:11][CH2:10]1
Reactant: COC(=O)c1ccc(C(=O)OC)cc1
Agent: [Pd]
Product: COC(=O)C1(C(=O)OC)CCCCC1

Procedure:
In the past 1,4-CHDM has been made by a process in which dimethyl terephthalate is subjected to hydrogenation using a catalyst of Ru or Pd carried on alumina to give dimethyl cyclohexanedicarboxylate, and then a side chain of the resulting ester is subjected to a hydrogenation reaction in the presence of a Cu—Zn oxide catalyst, to manufacture 1,4-CHDM, as mentioned, for example, in JP-W-8-510686. In addition, in JP-A-6-228028 is described a process for the manufacture of 1,4-CHDM where dialkyl terephthalate is subjected to hydrogenation to give dimethyl 1,4-cyclohexanedicarboxylate, and then the side chain of the product is hydrogenated using a catalyst containing Ru and Sn to manufacture 1,4-CHDM.
Reaction SMILES: C(OC=[C:5]([C:11](OCC)=O)[C:6]([O:8]CC)=O)C.[C:16]1([NH:22][NH2:23])[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1>CO>[C:16]1([N:22]2[C:6](=[O:8])[CH2:5][C:11]([C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=3)=[N:23]2)[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1
Reactant: NNc1ccccc1
Reactant: CCOC=C(C(=O)OCC)C(=O)OCC
Solvent: CO
Product: O=C1CC(c2ccccc2)=NN1c1ccccc1
Yield: 175.9 %

Procedure:
Diethyl ethoxymethylene-malonate (5.20 ml; 26 mmol) was added rapidly to 2.75 ml (28 mmol) of phenylhydrazine in 15 ml of methanol and the resulting mixture was refluxed for 4 hours. The mixture was cooled and concentrated in vacuo, and the residue was crystallized from ethanol to afford 5.82 g (97%) of 2,4-dihydro-2-phenyl-4-ethoxycarbonyl-3H-pyrazol-3-one (Formula III: R1 =Ph; R2 =H; R3 =C(O)OEt) as white needles, m.p. 106°-107° C.
Reaction SMILES: [CH2:1]([O:8][C:9]1[C:14]([CH3:15])=[C:13]([CH3:16])[C:12]([CH:17]=[O:18])=[C:11]([CH3:19])[C:10]=1[CH:20]([C:36]1[CH:41]=[CH:40][C:39]([F:42])=[CH:38][CH:37]=1)[CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][C:26]([O:28]CC1C=CC=CC=1)=[O:27])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[OH2:43]>O1CCOCC1.[Ag]=O>[CH2:1]([CH:25]([CH2:24][CH2:23][CH2:22][CH2:21][CH:20]([C:10]1[C:11]([CH3:19])=[C:12]([C:17]([OH:43])=[O:18])[C:13]([CH3:16])=[C:14]([CH3:15])[C:9]=1[O:8][CH2:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1)[C:36]1[CH:41]=[CH:40][C:39]([F:42])=[CH:38][CH:37]=1)[C:26]([OH:28])=[O:27])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: O
Reactant: Cc1c(C)c(OCc2ccccc2)c(C(CCCCCC(=O)OCc2ccccc2)c2ccc(F)cc2)c(C)c1C=O
Agent: O=[Ag]
Solvent: C1COCCO1
Product: Cc1c(C)c(C(=O)O)c(C)c(C(CCCCC(Cc2ccccc2)C(=O)O)c2ccc(F)cc2)c1OCc1ccccc1
Reaction time: 288 h

Procedure:
To a solution benzyl 7-(2-benzyloxy-5-formyl-3,4,6-trimethylphenyl)-7-(4-fluorophenyl)heptanoate (2.3 g) in dioxane (20 ml) and water (2 ml) was added silver oxide (II) (4.5 g) and the mixture was stirred for 12 days. Insoluble materials were filtered off and washed with ethyl acetate. The washing was combined with the filtrate and the mixture was concentrated. Ethyl acetate was added and the mixture was washed with water and saturated saline and dried with anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure and the residue was subjected to silica gel column chromatography to obtain benzyl 7-(2-benzyloxy-5-carboxy-3,4,6-trimethylphenyl)-7-(4fluorophenyl)heptanoic acid (1.5 g) (Compound 68). The physical properties and spectrum data thereof are shown in Tables 3 and 4.
Reaction SMILES: [CH2:1]=[C:2]([O:9][CH:10]1[CH:15]2[C:13]([N:16]3[CH:24]=[N:23][C:22]4[C:17]3=[N:18][C:19]([Cl:26])=[N:20][C:21]=4Cl)([CH2:14]2)[CH2:12][CH2:11]1)[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.[CH:27]1([NH2:32])[CH2:31][CH2:30][CH2:29][CH2:28]1>CO>[CH2:1]=[C:2]([O:9][CH:10]1[CH:15]2[C:13]([N:16]3[CH:24]=[N:23][C:22]4[C:17]3=[N:18][C:19]([Cl:26])=[N:20][C:21]=4[NH:32][CH:27]3[CH2:31][CH2:30][CH2:29][CH2:28]3)([CH2:14]2)[CH2:12][CH2:11]1)[C:3]1[CH:4]=[CH:5][CH:6]=[CH:7][CH:8]=1
Reactant: NC1CCCC1
Reactant: C=C(OC1CCC2(n3cnc4c(Cl)nc(Cl)nc43)CC12)c1ccccc1
Solvent: CO
Product: C=C(OC1CCC2(n3cnc4c(NC5CCCC5)nc(Cl)nc43)CC12)c1ccccc1
Yield: 90 %

Procedure:
To a solution of 12 (42 mg, 0.105 mmol) in methanol (2 ml) was added cyclopentylamine at room temperature, and stirring was continued for 6 hr for complete reaction. Solvent was removed under vacuum, and the residue obtained was purified by flash column chromatography using 7/3 petroleum ether/ethylacetate as eluent to furnish 45 mg of the product 15 (90% yield) as a gum.
Reaction SMILES: OC1C=CC(/C=C/C[N:11]2[CH2:16][CH2:15][CH:14]([C:17]3[CH:22]=[CH:21][C:20]([O:23][C:24]4[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=4)=[CH:19][CH:18]=3)[CH2:13][CH2:12]2)=CC=1OC.Br[CH2:33][C:34]1[O:35][C:36]2[CH:42]=[CH:41][CH:40]=[CH:39][C:37]=2[CH:38]=1>>[O:35]1[C:36]2[CH:42]=[CH:41][CH:40]=[CH:39][C:37]=2[CH:38]=[C:34]1[CH2:33][N:11]1[CH2:16][CH2:15][CH:14]([C:17]2[CH:22]=[CH:21][C:20]([O:23][C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=3)=[CH:19][CH:18]=2)[CH2:13][CH2:12]1
Reactant: BrCc1cc2ccccc2o1
Reactant: COc1cc(/C=C/CN2CCC(c3ccc(Oc4ccccc4)cc3)CC2)ccc1O
Product: c1ccc(Oc2ccc(C3CCN(Cc4cc5ccccc5o4)CC3)cc2)cc1

Procedure:
The same procedure was followed as in Example 11 using the compound (9) synthesized in Example 2 and 2-bromomethylbenzofuran to produce the above.
Reaction SMILES: [CH3:1][C:2]1[CH:11]=[C:10]([OH:12])[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[C:3]=1[OH:13].C(O[CH:17]([C:25]1[CH:30]=[CH:29][C:28]([O:31][CH3:32])=[CH:27][CH:26]=1)[CH2:18][CH2:19][CH2:20][CH2:21][C:22]([OH:24])=[O:23])C>CC1(C)C2(CS(O)(=O)=O)C(CC1CC2)=O.C1(C)C=CC=CC=1>[CH3:1][C:2]1[C:3](=[O:13])[C:4]2[C:9](=[CH:8][CH:7]=[CH:6][CH:5]=2)[C:10](=[O:12])[C:11]=1[CH:17]([C:25]1[CH:26]=[CH:27][C:28]([O:31][CH3:32])=[CH:29][CH:30]=1)[CH2:18][CH2:19][CH2:20][CH2:21][C:22]([OH:24])=[O:23]
Reactant: Cc1cc(O)c2ccccc2c1O
Reactant: CCOC(CCCCC(=O)O)c1ccc(OC)cc1
Agent: CC1(C)C2CCC1(CS(=O)(=O)O)C(=O)C2
Solvent: Cc1ccccc1
Product: COc1ccc(C(CCCCC(=O)O)C2=C(C)C(=O)c3ccccc3C2=O)cc1
Temperature: 60 °C
Yield: 44.6 %

Procedure:
D-Camphor-10-sulfonic acid (0.1 g) was added to a toluene solution (50 ml) of 2-methyl-1,4-naphthohydroquinone (3.6 g, 0.02 mole) and 6-ethoxy-6-(4-methoxyphenyl)hexanoic acid (5.6 g, 0.021 mole), and the mixture was heated at 60° C. for 18 hours, with stirring. After cooling, the solvent was distilled off under reduced pressure, and then tetrahydrofuran (20 ml) was added to the residue. A 10% aqueous solution of ferric chloride was added to the solution, followed by stirring for 10 minutes, and the reaction product was extracted with ethyl acetate. The organic layer was washed with water, dried and concentrated under reduced pressure. The residue was chromatographed on a silica gel column, and elution was effected with isopropyl ether to give 6-(3-methyl-1,4-naphthoquinon-2-yl)-6-(4-methoxyphenyl)hexanoic acid (3.5 g, 45%). This product was recrystallized from isopropyl ether. Its typical physical properties and nuclear magnetic resonance spectrum data are shown in Table 1. By following the procedure of this Example, the Compound No. 21 was prepared.
Reaction SMILES: [C:1]1([C:7]([C:32]2[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=2)([C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)[N:8]2[N:12]=[N:11][C:10]([C:13]3[CH:14]=[CH:15][C:16]4[NH:17][C:18]5[C:23]([C:24]=4[CH:25]=3)=[CH:22][CH:21]=[CH:20][CH:19]=5)=[N:9]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[H-].[Na+].[Cl:40][C:41]1[CH:42]=[C:43]([CH:46]=[CH:47][CH:48]=1)[CH2:44]Cl.Cl>CS(C)=O>[Cl:40][C:41]1[CH:42]=[C:43]([CH:46]=[CH:47][CH:48]=1)[CH2:44][N:17]1[C:16]2[CH:15]=[CH:14][C:13]([C:10]3[N:11]=[N:12][N:8]([C:7]([C:1]4[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=4)([C:26]4[CH:27]=[CH:28][CH:29]=[CH:30][CH:31]=4)[C:32]4[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=4)[N:9]=3)=[CH:25][C:24]=2[C:23]2[C:18]1=[CH:19][CH:20]=[CH:21][CH:22]=2
Reactant: c1ccc(C(c2ccccc2)(c2ccccc2)n2nnc(-c3ccc4[nH]c5ccccc5c4c3)n2)cc1
Reactant: ClCc1cccc(Cl)c1
Agent: Cl
Agent: [H-]
Agent: [Na+]
Solvent: CS(C)=O
Product: Clc1cccc(Cn2c3ccccc3c3cc(-c4nnn(C(c5ccccc5)(c5ccccc5)c5ccccc5)n4)ccc32)c1
Temperature: 25 °C
Reaction time: 0.5 h

Procedure:
3-[2-(Triphenylmethyl)-2H-tetrazol-5-yl]-9H-carbazole (200 mg, 0.42 mmol) was dissolved in methyl sulfoxide (1.5 mL). Sodium hydride (34 mg, 60%, 0.85 mmol) was added, and the resulting suspension was stirred for 30 min at room temperature. 3-Chlorobenzyl chloride (85 μL, 108 mg, 0.67 mmol) was added, and the stirring was continued at 40° C. for 18 hours. The reaction mixture was cooled to ambient temperature and poured into 0.1 N hydrochloric acid (aq.) (15 mL) The precipitated solid was filtered off and washed with water (3×10 mL) to furnish 9-(3-chlorobenzyl)-3-[2-(triphenylmethyl)-2H-tetrazol-5-yl]-9H-carbazole, which was dissolved in a mixture of tetrahydrofuran and 6 N hydrochloric acid (aq.) (9:1) (10 mL) and stirred at room temperature for 18 hours. The reaction mixture was poured into water (100 mL). The solid was filtered off and rinsed with water (3×10 mL) and dichloromethane (3×10 mL) to yield the title compound (127 mg). No further purification was necessary.
Reaction SMILES: [CH3:1]O.[CH3:3][O:4][C:5]1[CH:10]=[C:9]([O:11][CH3:12])[N:8]=[C:7]([S:13][C:14](C)([CH2:17][CH3:18])[CH:15]=[O:16])[N:6]=1.B.[Na]>O>[CH3:12][O:11][C:9]1[CH:10]=[C:5]([O:4][CH3:3])[N:6]=[C:7]([S:13][CH:14]([CH:17]([CH3:18])[CH3:1])[CH2:15][OH:16])[N:8]=1
Reactant: CO
Reactant: CCC(C)(C=O)Sc1nc(OC)cc(OC)n1
Agent: B
Agent: [Na]
Solvent: O
Product: COc1cc(OC)nc(SC(CO)C(C)C)n1

Procedure:
To a methanol solution of 2-(4,6-dimethoxy-2-pyrimidinylthio)-methyl butyraldehyde (1.5 g) was added sodium boron hydride (0.2 g), followed by a five-minute stirring at room temperature. Water was then added to the reaction liquid, followed by extraction with ethyl acetate, water-washing of the resulting organic layer and drying thereof in that order. After the removal of the drying agent from the reaction product under filtration, followed by separation of ethyl acetate under reduced pressure distillation, there was obtained an oily substance that was then purified by silica gel column chromatography to obtain the desired 2-(4,6-dimethoxy-2-pyrimidinylthio)-3-methylbutanol (1.3 g) n20D 1.5445.
Reaction SMILES: [C:1]([OH:5])(=[O:4])[CH2:2][CH3:3].[C:6]([OH:10])(=[O:9])[CH2:7][CH3:8].[OH:11][C@H:12]1[CH2:17][CH2:16][C@H:15]2[C@H:18]3[C@H:29]([CH2:30][CH2:31][C@:13]12[CH3:14])[C@:26]1([CH2:27][OH:28])[C:21](=[CH:22][C:23](=[O:32])[CH2:24][CH2:25]1)[CH2:20][CH2:19]3.ClC1C(=O)C(C#N)=C(C#N)C(=O)C=1Cl>O1CCOCC1>[C:1]([OH:5])(=[O:4])[CH2:2][CH3:3].[C:6]([OH:10])(=[O:9])[CH2:7][CH3:8].[OH:11][C@H:12]1[CH2:17][CH2:16][C@H:15]2[C@H:18]3[C@H:29]([CH2:30][CH2:31][C@:13]12[CH3:14])[C@:26]1([CH2:27][OH:28])[C:21](=[CH:22][C:23](=[O:32])[CH:24]=[CH:25]1)[CH2:20][CH2:19]3
Reactant: C[C@]12CC[C@H]3[C@@H](CCC4=CC(=O)CC[C@@]43CO)[C@@H]1CC[C@@H]2O
Agent: N#CC1=C(C#N)C(=O)C(Cl)=C(Cl)C1=O
Solvent: CCC(=O)O
Solvent: C1COCCO1
Product: C[C@]12CC[C@H]3[C@@H](CCC4=CC(=O)C=C[C@@]43CO)[C@@H]1CC[C@@H]2O

Procedure:
17β,19-Dihydroxy-4-androsten-3-one dipropionate and dichlorodicyanobenzoquinone are refluxed in anhydrous dioxane for a period of 48 hours. The mixture is cooled and filtered and the filtrate concentrated under vacuum. Methylenechloride is added and the resulting mixture filtered. The filtrate is washed well with water, dried over sodium sulfate and the solvent removed. Chromatography of the residue on silica gel and elution with methylenechloride provides a solid which is crystallized from an acetone-hexane solution to yield the desired 17β,19-dihydroxy-1,4-androstadien-3-one dipropionate.
Reaction SMILES: Br[C:2]1[CH:3]=[C:4]([N+:16]([O-:18])=[O:17])[C:5]([NH:8][C:9]2[CH:14]=[CH:13][CH:12]=[C:11]([NH2:15])[CH:10]=2)=[N:6][CH:7]=1.[F:19][C:20]1[CH:25]=[CH:24][C:23](B(O)O)=[CH:22][CH:21]=1>COCCOC.C([O-])([O-])=O.[Na+].[Na+]>[F:19][C:20]1[CH:25]=[CH:24][C:23]([C:2]2[CH:3]=[C:4]([N+:16]([O-:18])=[O:17])[C:5]([NH:8][C:9]3[CH:14]=[CH:13][CH:12]=[C:11]([NH2:15])[CH:10]=3)=[N:6][CH:7]=2)=[CH:22][CH:21]=1
Reactant: OB(O)c1ccc(F)cc1
Reactant: Nc1cccc(Nc2ncc(Br)cc2[N+](=O)[O-])c1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: COCCOC
Product: Nc1cccc(Nc2ncc(-c3ccc(F)cc3)cc2[N+](=O)[O-])c1
Temperature: 80 °C
Yield: 62.4 %

Procedure:
A mixture of PdCl2dppf (300 mg, 0.4 mmol), N-(5-bromo-3-nitro-pyridin-2-yl)-benzene-1,3-diamine (Preparation P1, 2.5 g, 8.2 mmol) and 4-fluorophenylboronic acid (1.4 g, 10 mmol) in DME (16 ml) and 2N Na2CO3 (16 ml) was deoxygenated by evacuate/fill N2 (×3), then stirred and heated at 80° C. under N2 for 4 hours. After cooling to RT the mixture was partitioned between EtOAc/H2O and then filtered through Celite. The organic layer was washed with brine (×1) then dried (MgSO4), filtered and evaporated. The residue was purified by chromatography on silica (10→50% EtOAc/petrol) to give the title compound (1.66 g) as a dark red/brown solid. 1H NMR (400 MHz, DMSO-d6): 9.85 (1H, s), 8.87 (1H, d), 8.70 (1H, d), 7.82 (2H, dd), 7.33 (2H, t), 7.02 (1H, t), 6.92-6.81 (2H, m), 6.40 (1H, d), 5.15 (2H, s).
Reaction SMILES: C(O[B:5]1[O:9][C:8]([CH3:11])([CH3:10])[C:7]([CH3:13])([CH3:12])[O:6]1)(C)C.C([Li])CCC.[F:19][C:20]1[CH:21]=[C:22]([CH:30]=[C:31]([F:33])[CH:32]=1)[O:23][CH:24]1[CH2:29][CH2:28][O:27][CH2:26][CH2:25]1>>[F:33][C:31]1[CH:30]=[C:22]([O:23][CH:24]2[CH2:25][CH2:26][O:27][CH2:28][CH2:29]2)[CH:21]=[C:20]([F:19])[C:32]=1[B:5]1[O:6][C:7]([CH3:12])([CH3:13])[C:8]([CH3:10])([CH3:11])[O:9]1
Reactant: CC(C)OB1OC(C)(C)C(C)(C)O1
Reactant: Fc1cc(F)cc(OC2CCOCC2)c1
Agent: [Li]CCCC
Product: CC1(C)OB(c2c(F)cc(OC3CCOCC3)cc2F)OC1(C)C
Yield: 33 %

Procedure:
Method 3 was followed using 2-isopropoxy-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (1.5 equiv.), butyllithium (1.3 equiv.) and 4-(3,5-difluorophenoxy)tetrahydro-2H-pyran (1.0 equiv.) to give 2-(2,6-difluoro-4-((tetrahydro-2H-pyran-4-yl)oxy)phenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane in 33% yield. 1H NMR (400 MHz, <cdcl3>) δ ppm 1.21-1.34 (m, 12H), 1.78 (dtd, J=12.72, 8.31, 8.31, 3.91 Hz, 2H), 1.93-2.09 (m, 2H), 3.59 (ddd, J=11.64, 8.31, 3.13 Hz, 2H), 3.89-4.01 (m, 2H), 4.48 (tt, J=7.78, 3.77 Hz, 1H), 6.40 (d, J=9.39 Hz, 2H).
Reaction SMILES: Cl.[N:2]1[C:11]2[C:6](=[CH:7][C:8]([C:12](Cl)=[O:13])=[CH:9][CH:10]=2)[CH:5]=[CH:4][CH:3]=1.[C:15]12([OH:25])[CH2:24][CH:19]3[CH2:20][CH:21]([CH2:23][CH:17]([CH2:18]3)[CH2:16]1)[CH2:22]2.O>N1C=CC=CC=1>[N:2]1[C:11]2[C:6](=[CH:7][C:8]([C:12]([O:25][C:15]34[CH2:22][CH:21]5[CH2:20][CH:19]([CH2:18][CH:17]([CH2:23]5)[CH2:16]3)[CH2:24]4)=[O:13])=[CH:9][CH:10]=2)[CH:5]=[CH:4][CH:3]=1
Reactant: OC12CC3CC(CC(C3)C1)C2
Reactant: O=C(Cl)c1ccc2ncccc2c1
Agent: Cl
Solvent: c1ccncc1
Solvent: O
Product: O=C(OC12CC3CC(CC(C3)C1)C2)c1ccc2ncccc2c1
Temperature: 70 °C
Reaction time: 16 h
Yield: 31.5 %

Procedure:
6-Quinolinecarbonyl chloride hydrochloride (0.76 g, 3.3 mmol) in pyridine (2 mL) was added to a solution of 1-adamantanol (0.60 g, 3.9 mmol) in pyridine (8 mL). The reaction was stirred at 70° C. for 16 h. To the stirring reaction mixture was added water (100 mL) which caused the product to precipitate. This precipitate was filtered and then washed with water (3×25 mL). The filter cake was dissolved in ethanol (20 mL) and water was then added to the cloud point (16 mL). The crystallizing solution was allowed to stand for 15 h. Filtering and drying under high vacuum for 7 h provided 0.32 g (26%) of (61) as light brown needle-like crystals:
Reaction SMILES: [CH3:1][N:2]1[C:11]2[C:6](=[CH:7][CH:8]=[C:9]([N+:12]([O-])=O)[CH:10]=2)[CH2:5][CH2:4][CH2:3]1>[Pd].CO>[NH2:12][C:9]1[CH:10]=[C:11]2[C:6]([CH2:5][CH2:4][CH2:3][N:2]2[CH3:1])=[CH:7][CH:8]=1
Reactant: CN1CCCc2ccc([N+](=O)[O-])cc21
Agent: [Pd]
Solvent: CO
Product: CN1CCCc2ccc(N)cc21
Reaction time: 72 h
Yield: 57 %

Procedure:
A mixture of 1-methyl-7-nitro-1,2,3,4-tetrahydroquinoline (D2) (5.35 g, 27.9 mmol) and 10% palladium on charcoal (2 g, 54% water) in methanol (150 ml) was hydrogenated at atmospheric pressure and ambient temperature temperature for 3 d. The catalyst was filtered off and washed with further methanol. The combined filtrated and washings were concentrated in vacuo to give the crude product, which was purified by flash column chromatography. Elution with 5-10% EtOAc/DCM gave the title compound as a brown oil (2.58 g). 1H NMR (250 MHz, CDCl3) δ(ppm): 6.73 (dd, 1H), 5.99 (m, 2H), 3.49 (br, 1H), 3.18 (m, 2H), 2.84 (s, 3H), 2.66 (t, 2H), 1.93 (m, 2H).