Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Cl:1][C:2]1[C:10]2[N:9]=[C:8]3[NH:11][CH2:12][CH2:13][CH2:14][N:7]3[C:6]=2[C:5]([N+:15]([O-:17])=[O:16])=[CH:4][CH:3]=1.[Cl:18][C:19]1[CH:24]=[C:23]([Cl:25])[CH:22]=[CH:21][C:20]=1I.N1C=CC=CC=1C1C=CC=CN=1.C(=O)([O-])[O-].[Cs+].[Cs+]>CN(C)C=O.C(OCC)(=O)C.[Cu]I>[Cl:1][C:2]1[C:10]2[N:9]=[C:8]3[N:11]([C:22]4[CH:21]=[CH:20][C:19]([Cl:18])=[CH:24][C:23]=4[Cl:25])[CH2:12][CH2:13][CH2:14][N:7]3[C:6]=2[C:5]([N+:15]([O-:17])=[O:16])=[CH:4][CH:3]=1
Reactant: Clc1ccc(I)c(Cl)c1
Reactant: O=[N+]([O-])c1ccc(Cl)c2nc3n(c12)CCCN3
Agent: [Cu]I
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: CN(C)C=O
Solvent: CCOC(C)=O
Product: O=[N+]([O-])c1ccc(Cl)c2nc3n(c12)CCCN3c1ccc(Cl)cc1Cl
Temperature: 150 °C
Reaction time: 12 h
Yield: 4.7 %

Procedure:
A mixture of 9-chloro-6-nitro-1,2,3,4-tetrahydropyrimido[1,2-a]benzimidazole (Reference Example 108; 10.0 g, 39.6 mmol), 2,4-dichloro-1-iodobenzene (54.0 g, 197.9 mmol), copper(I) iodide (7.57 g, 39.6 mmol), 2,2′-bipyridyl (12.3 g, 79.2 mmol) and cesium carbonate (25.8 g, 79.2 mmol) in N,N-dimethylformamide (600 mL) was stirred at 150° C. for 12 hr. The mixture was diluted with ethyl acetate, washed with water, dried over anhydrous sodium sulfate and concentrated in vacuo. The residue was purified by flash chromatography on silica gel eluting with a 10-25% ethyl acetate/n-hexane gradient mixture. The filtrate was concentrated in vacuo to give the title compound (750 mg, 1.88 mmol, 5%) as a light yellow amorphous.
Reaction SMILES: [CH2:1]([N:3]([CH2:24][CH3:25])[C:4]1[CH:9]=[CH:8][C:7]([N:10]=[N:11][C:12]2[CH:17]=[CH:16][C:15]([C:18]([OH:20])=[O:19])=[C:14]([C:21]([OH:23])=[O:22])[CH:13]=2)=[CH:6][CH:5]=1)[CH3:2].[CH3:26]O>>[CH2:24]([N:3]([CH2:1][CH3:2])[C:4]1[CH:9]=[CH:8][C:7]([N:10]=[N:11][C:12]2[CH:17]=[CH:16][C:15]([C:18]([O:20][CH3:26])=[O:19])=[C:14]([C:21]([OH:23])=[O:22])[CH:13]=2)=[CH:6][CH:5]=1)[CH3:25]
Reactant: CO
Reactant: CCN(CC)c1ccc(N=Nc2ccc(C(=O)O)c(C(=O)O)c2)cc1
Product: CCN(CC)c1ccc(N=Nc2ccc(C(=O)OC)c(C(=O)O)c2)cc1

Procedure:
1.6 Parts of the anhydride of N,N-diethyl-4(3,4-dicarboxyphenylazo)aniline is dissolved in 25 parts of methanol and the solution heated under reflux for 2 hours. The solution is then evaporated in vacuo to give N,N-diethyl-4(3-carboxy-4-carbomethoxyphenylazo)aniline which gives an orange solution in acetone with λmax 453.
Reaction SMILES: [F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[N:9]1[C:17](=[O:18])[C:16]2[C@@H:15]3[C:19]([CH3:21])([CH3:20])[C@@:12]([CH3:22])([CH2:13][CH2:14]3)[C:11]=2[NH:10]1.[CH3:23][O:24][C:25]1[CH:32]=[CH:31][C:28]([CH2:29]Br)=[CH:27][CH:26]=1>[I-].C([N+](CCCC)(CCCC)CCCC)CCC.CN(C)C=O>[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[N:9]1[C:17](=[O:18])[C:16]2[C@@H:15]3[C:19]([CH3:21])([CH3:20])[C@@:12]([CH3:22])([CH2:13][CH2:14]3)[C:11]=2[N:10]1[CH2:29][C:28]1[CH:31]=[CH:32][C:25]([O:24][CH3:23])=[CH:26][CH:27]=1
Reactant: COc1ccc(CBr)cc1
Reactant: CC1(C)[C@@H]2CC[C@@]1(C)c1[nH]n(-c3ccc(F)cc3F)c(=O)c12
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: [I-]
Solvent: CN(C)C=O
Product: COc1ccc(Cn2c3c(c(=O)n2-c2ccc(F)cc2F)[C@H]2CC[C@]3(C)C2(C)C)cc1
Temperature: 80 °C
Yield: 77.9 %

Procedure:
A mixture of (4S,7R)-2-(2,4-difluoro-phenyl)-7,8,8-trimethyl-1,2,4,5,6,7-hexahydro-4,7-methano-indazol-3-one (Intermediate 14; 150 mg, 0.49 mmol), tetrabutylammonium iodide (181 mg, 0.49 mmol) and 4-methoxybenzyl bromide (280 μL, 1.94 mmol) in dimethylformamide (3 mL) was heated at 80° C. overnight. The solvent was evaporated, dichloromethane (50 mL) was added and the solution was washed with water (2×20 mL), saturated aqueous sodium thiosulfate (20 mL), and brine (20 mL). The solution was dried (magnesium sulfate), filtered, evaporated, and purified by column chromatography, eluting with 60-75% ethyl acetate/petroleum ether, and dried under high vacuum overnight to give (4S,7R)-2-(2,4-difluoro-phenyl)-1-(4-methoxy-benzyl)-7,8,8-trimethyl-1,2,4,5,6,7-hexahydro-4,7-methano-indazol-3-one (162 mg, 78%). APCI(+)-MS (M+H) 425.
Reaction SMILES: [Cl:1][C:2]1[C:3]([S:11][CH3:12])=[N:4][CH:5]=[C:6]([CH:8]([OH:10])[CH3:9])[CH:7]=1.[H-].[Na+].[CH2:15](Br)[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1>CN(C=O)C.O>[CH2:15]([O:10][CH:8]([C:6]1[CH:7]=[C:2]([Cl:1])[C:3]([S:11][CH3:12])=[N:4][CH:5]=1)[CH3:9])[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1
Reactant: CSc1ncc(C(C)O)cc1Cl
Reactant: BrCc1ccccc1
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: O
Product: CSc1ncc(C(C)OCc2ccccc2)cc1Cl
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 82.6 %

Procedure:
3-Chloro-5-(1-hydroxyethyl)-2-methylthiopyridine (21.9 g, 0.108 mol) was dissolved with stirring in anhydrous DMF (250 mL) and 60% sodium hydride (5 g, 0.125 mol) added in portions. The mixture was stirred at room temperature for 30 minutes and benzyl bromide (17.6 g, 0.103 mol) added dropwise. The mixture was then stirred at room temperature for four hours, diluted with water (400 mL) and extracted three times with ethyl acetate (100 mL). The combined organic extracts were washed twice with water (200 mL) and saturated sodium chloride solution (100 mL), dried over anhydrous sodium sulphate, and evaporated to dryness. Purification of the residue by chromatography over silica (0-5% ethyl acetate:hexane) gave the desired product (25.0 g, 79%) as a pale yellow oil.
Reaction SMILES: C(=O)([O-])[O-].[K+].[K+].[C:7]([NH:11][C:12]([C@@H:14]1[CH2:19][N:18]([CH:20]=[O:21])[CH2:17][CH2:16][N:15]1C(=O)C(F)(F)F)=[O:13])([CH3:10])([CH3:9])[CH3:8]>O.C(O)C(C)C>[C:7]([NH:11][C:12]([C@@H:14]1[CH2:19][N:18]([CH:20]=[O:21])[CH2:17][CH2:16][NH:15]1)=[O:13])([CH3:10])([CH3:8])[CH3:9]
Reactant: CC(C)(C)NC(=O)[C@@H]1CN(C=O)CCN1C(=O)C(F)(F)F
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CC(C)CO
Product: CC(C)(C)NC(=O)[C@@H]1CN(C=O)CCN1
Yield: 136.3 %

Procedure:
A solution of 25.5 g (184.5 mmol) of potassium carbonate in 130 ml of water was added to 15.0 g (48.5 mmol) of (S)-4-formyl-1-(trifluoroacetyl)-piperazine-2-carboxylic acid tert-butylamide in 130 ml of isobutyl alcohol and the mixture was heated at 60° to 65° C. for 1 hour. After phase separation, the aqueous phase was extracted with 100 ml of isobutyl alcohol and the combined organic phases were evaporated to give 14.10 g of the crude title compound (still containing solvent) in the form of a light yellow oil. Other data concerning the title compound was:
Reaction SMILES: [OH:1][C:2]([CH3:23])([CH3:22])[C:3]([N:5]1[CH2:10][CH2:9][N:8](NC(OCC2C=CC=CC=2)=O)[CH2:7][CH2:6]1)=[O:4]>CO.[Pd]>[OH:1][C:2]([CH3:23])([CH3:22])[C:3]([N:5]1[CH2:6][CH2:7][NH:8][CH2:9][CH2:10]1)=[O:4]
Reactant: CC(C)(O)C(=O)N1CCN(NC(=O)OCc2ccccc2)CC1
Agent: [Pd]
Solvent: CO
Product: CC(C)(O)C(=O)N1CCNCC1
Reaction time: 8 h
Yield: 100 %

Procedure:
Benzyl 4-(2-hydroxy-2-methylpropionyl)piperazine-1-carbamate (2.82 g, 9.20 mmol) synthesized in Production example 28-1 was dissolved in methanol (100 ml) under nitrogen atmosphere; 10% palladium on carbon (50% wet, 1.96 g) was added thereto, the reaction system was purged with hydrogen at atmospheric pressure; and the reaction mixture was stirred overnight. After the reaction system was purged with nitrogen, the catalyst was filtered out, and washed with methanol, then the solvent, together with the filtrate and the washing solution, was distilled off. The residue was dried under reduced pressure to yield the title compound (1.58 g, 9.20 mmol, quantitative) as a colorless oil.
Reaction SMILES: FC(F)(F)S(O[C:7]1[CH:16]=[CH:15][C:14]2[C:9](=[C:10]([C:19]#[N:20])[CH:11]=[C:12]([O:17][CH3:18])[CH:13]=2)[CH:8]=1)(=O)=O.[CH3:23][O:24][C:25]1[CH:26]=[C:27](OB(O)O)[CH:28]=[CH:29][CH:30]=1>>[CH3:18][O:17][C:12]1[CH:11]=[C:10]([C:19]#[N:20])[C:9]2[C:14]([CH:13]=1)=[CH:15][CH:16]=[C:7]([C:29]1[CH:28]=[CH:27][CH:26]=[C:25]([O:24][CH3:23])[CH:30]=1)[CH:8]=2
Reactant: COc1cccc(OB(O)O)c1
Reactant: COc1cc(C#N)c2cc(OS(=O)(=O)C(F)(F)F)ccc2c1
Product: COc1cccc(-c2ccc3cc(OC)cc(C#N)c3c2)c1
Yield: 25 %

Procedure:
The compound is prepared by the reaction of 8-cyano-6-methoxynaphthalene-2-yl trifluoromethanesulfonate (466 mg, 1.4 mmol, 1 eq) with 3-methoxyphenylboric acid (260 mg, 1.7 mmol, 1.2 eq) according to method A over night. Purification by column chromatography with hexane/ethyl acetate 7/3 as the eluent yielded the desired compound in a yield of 25%, 113 mg.
Reaction SMILES: [CH2:1]([O:3][C:4]([C:6]1[N:7]=[C:8]([NH:11][C:12]2[CH:17]=[CH:16][C:15]([Cl:18])=[CH:14][CH:13]=2)[S:9][CH:10]=1)=[O:5])[CH3:2].Br.[Cl:20][C:21]1[CH:29]=[C:28]([Cl:30])[CH:27]=[CH:26][C:22]=1[C:23](Cl)=[O:24].CCN(CC)CC>C(Cl)Cl>[CH2:1]([O:3][C:4]([C:6]1[N:7]=[C:8]([N:11]([C:12]2[CH:17]=[CH:16][C:15]([Cl:18])=[CH:14][CH:13]=2)[C:23](=[O:24])[C:22]2[CH:26]=[CH:27][C:28]([Cl:30])=[CH:29][C:21]=2[Cl:20])[S:9][CH:10]=1)=[O:5])[CH3:2]
Reactant: CCOC(=O)c1csc(Nc2ccc(Cl)cc2)n1
Reactant: O=C(Cl)c1ccc(Cl)cc1Cl
Agent: Br
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: CCOC(=O)c1csc(N(C(=O)c2ccc(Cl)cc2Cl)c2ccc(Cl)cc2)n1

Procedure:
A mixture of 2.58 g (7.1 mmol) 2-(4-Chloro-phenylamino)-thiazole-4-carboxylic acid ethyl ester; hydrobromide, 2.24 g (10.7 mmol) 2,4-Dichlorobenzoyl chloride and 2.96 ml (21.4 mmol) NEt3 in 30 ml DCM was stirred at room temperature for 24 h. After evaporation of the volatiles the residue was taken up in MeOH and purified with flash column chromatography on silica eluting with a gradient of heptane/ethyl acetate to yield after evaporation of the product fractions 2.81 g (87%) of the title compound. MS (m/e): 457.1 (MH+, 100%)
Reaction SMILES: [NH:1]1[CH:5]=[CH:4][N:3]=[CH:2]1.C(=O)([O-])[O-].[K+].[K+].Br[CH:13]([C:16]1[N:21]=[CH:20][C:19]([C:22]2[CH:29]=[CH:28][C:25]([C:26]#[N:27])=[CH:24][CH:23]=2)=[CH:18][CH:17]=1)[CH2:14][CH3:15].C(=O)(O)[O-].[Na+]>CN(C=O)C>[N:1]1([CH:13]([C:16]2[N:21]=[CH:20][C:19]([C:22]3[CH2:29][CH2:28][C:25]([C:26]#[N:27])=[CH:24][CH:23]=3)=[CH:18][CH:17]=2)[CH2:14][CH3:15])[CH:5]=[CH:4][N:3]=[CH:2]1
Reactant: c1c[nH]cn1
Reactant: CCC(Br)c1ccc(-c2ccc(C#N)cc2)cn1
Agent: O=C([O-])O
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: CCC(c1ccc(C2=CC=C(C#N)CC2)cn1)n1ccnc1
Temperature: 70 °C
Yield: 13.8 %

Procedure:
To a solution of imidazole (0.034 g, 0.332 mmol) in DMF (3 ml) was added potassium carbonate (0.11 g, 0.83 mmol) and 4-(6-(1-bromopropyl)pyridin-3-yl)benzonitrile (0.090 g) under nitrogen and the solution was heated to 70° C. for 3 h. After cooling the contents to rt, sodium bicarbonate was added, extracted with ethyl acetate (50 mL), the organic layer separated, the organic layer dried over sodium sulphate and distilled off to obtain the crude product. The compound was purified by preparative TLC using (2000μ; 5% MeOH/DCM) to provide 4-(6-(1-(1H-imidazol-1-yl)propyl)pyridin-3-yl)cyclohexa-1,3-dienecarbonitrile (0.012 g, 13.9% yield). 1H NMR (400 MHz DMSO-d6): δ 8.96 (d, 1H), 8.19 (dd, 1H), 7.96 (d, 5H); 7.47 (d, 1H), 7.39 (s, 1H), 7.01 (s, 1H), 5.45 (t, 1H), 2.26-2.23 (m, 2H), 0.84 (t, 3H): LC-MS m/z calcd for [M+H]+ 289.14. found 289.0.
Reaction SMILES: C([O-])(=O)C.[K+].Br[C:7]1[CH:8]=[CH:9][C:10]2[C:11]([CH:15]=1)=[N:12][O:13][N:14]=2.C(=O)([O-])[O-].[Na+].[Na+].Br[C:23]1[CH:31]=[CH:30][CH:29]=[CH:28][C:24]=1[N:25]([CH3:27])[CH3:26]>CN(C=O)C.O>[N:14]1[O:13][N:12]=[C:11]2[CH:15]=[C:7]([C:23]3[CH:31]=[CH:30][CH:29]=[CH:28][C:24]=3[N:25]([CH3:27])[CH3:26])[CH:8]=[CH:9][C:10]=12
Reactant: CN(C)c1ccccc1Br
Reactant: Brc1ccc2nonc2c1
Agent: CC(=O)[O-]
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CN(C)C=O
Product: CN(C)c1ccccc1-c1ccc2nonc2c1
Temperature: 80 °C
Reaction time: 6 h

Procedure:
523 mg (1.65 eq.) bis(pinacolato)diboran, 552 mg (4.5 eq.) potassium acetate and 51 mg (0.01 eq.) PdCl(dppf)-CH2Cl2 are added to a solution of 373 mg 5-bromo-benzo[1,2,5]oxadiazole in 8 mL DMF and heated to 80° C. under continuous stirring for 6 hours. 662 mg (5 eq.) sodium carbonate in 3.3 mL water are added together with 500 mg (1 eq.) 2-bromo-N,N-dimethylaniline and 51 mg (0.01 eq.) PdCl(dppf)-CH2Cl2 to the reaction mixture, which is stirred for another 18 hours at 80° C., cooled to room temperature and extracted with ethyl acetate and water. The combined organic phases are washed with brine, dried over magnesium sulfate and evaporated. The residue is column chromatographed (hexane, then hexane/ethyl acetate 8:1) to yield the desired product as an orange resin. MS(ES+): 240 (M+1).
Reaction SMILES: [H-].[Na+].[C:3]([C:5]1[C:10]([C:11]#[N:12])=[C:9]([OH:13])[CH:8]=[CH:7][C:6]=1[OH:14])#[N:4].[CH:15]([N:18]([CH:23]([CH3:25])[CH3:24])[C:19](=[O:22])[CH2:20]Br)([CH3:17])[CH3:16]>CN(C)C=O>[CH:15]([N:18]([CH:23]([CH3:25])[CH3:24])[C:19](=[O:22])[CH2:20][O:14][C:6]1[CH:7]=[CH:8][C:9]([OH:13])=[C:10]([C:11]#[N:12])[C:5]=1[C:3]#[N:4])([CH3:17])[CH3:16]
Reactant: CC(C)N(C(=O)CBr)C(C)C
Reactant: N#Cc1c(O)ccc(O)c1C#N
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: CC(C)N(C(=O)COc1ccc(O)c(C#N)c1C#N)C(C)C
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 59.8 %

Procedure:
960 mg of sodium hydride (50% in oil) were added to a solution of 1.6 g of 2,3-dicyano-4-hydroxy-phenol in 100 ml of dimethylformamide, and after stirring for 30 minutes at ambient temperature, then 2.3 g of N,N-bis(isopropyl)-2-bromoacetamide (preparation 8) were added. After stirring for 48 hours, the solvent was evaporated under reduced pressure and 200 ml of 2N hydrochloric acid were added. Extraction was carried out with ethyl acetate and the organic phase was dried over magnesium sulfate, filtered and evaporated under reduced pressure. The residue was chromatographed, eluting with a cyclohexane-ethyl acetate mixture (50/50), then with pure ethyl acetate, and finally an ethyl acetate-methanol mixture (98/2) to obtain 1.8 g of the expected product is obtained which was used as is for the following stage.
Reaction SMILES: [S:1](Cl)([CH3:4])(=[O:3])=[O:2].[C:6]([O:10][C:11]([N:13]1[CH2:18][CH:17]([CH2:19][OH:20])[CH2:16][CH:15]([N:21]2[C:30]3[CH:29]=[CH:28][CH:27]=[C:26]([Cl:31])[C:25]=3[C:24]3=[N:32][O:33][C:34]([CH3:35])=[C:23]3[C:22]2=[O:36])[CH2:14]1)=[O:12])([CH3:9])([CH3:8])[CH3:7]>CN(C1C=CN=CC=1)C.N1C=CC=CC=1>[C:6]([O:10][C:11]([N:13]1[CH2:18][CH:17]([CH2:19][O:20][S:1]([CH3:4])(=[O:3])=[O:2])[CH2:16][CH:15]([N:21]2[C:30]3[CH:29]=[CH:28][CH:27]=[C:26]([Cl:31])[C:25]=3[C:24]3=[N:32][O:33][C:34]([CH3:35])=[C:23]3[C:22]2=[O:36])[CH2:14]1)=[O:12])([CH3:9])([CH3:8])[CH3:7]
Reactant: CS(=O)(=O)Cl
Reactant: Cc1onc2c1c(=O)n(C1CC(CO)CN(C(=O)OC(C)(C)C)C1)c1cccc(Cl)c21
Agent: CN(C)c1ccncc1
Solvent: c1ccncc1
Product: Cc1onc2c1c(=O)n(C1CC(COS(C)(=O)=O)CN(C(=O)OC(C)(C)C)C1)c1cccc(Cl)c21
Temperature: 25 °C
Reaction time: 8 h
Yield: 78.8 %

Procedure:
Add DMAP (5 mg, cat.) and mesyl chloride (0.2 mL, 2.5 mmol) to a solution of 3-(9-chloro-3-methyl-4-oxo-5H-isoxazolo[4,3-c]quinolin-5-yl)-5-hydroxymethyl-piperidine-1-carboxylic acid tert-butyl ester (0.95 g, 2.1 mmol) in pyridine (10 mL). Stir overnight at room temperature then concentrate to dryness. Partition between EtOAc, and water. Extract 2× with EtOAc. Wash the combined organics 3× with brine, dry over Na2SO4, filter and concentrate to dryness to afford the title compound (0.87 g, 79%) as a white solid as a mixture of cis isomers. MS(IS) 526.0 (M+); TLC (50% EtOAc/hexanes) Rf=0.65.
Reaction SMILES: C([O:8][C:9](=[O:21])[NH:10][C@@H:11]([C@H:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])[CH3:15])[CH2:12]O)C1C=CC=CC=1.[H-].[Na+].[CH3:24][O:25][C:26]1[CH:33]=[CH:32][C:29]([CH2:30]Cl)=[CH:28][CH:27]=1.CCOC(C)=O>CN(C=O)C.[I-].C([N+](CCCC)(CCCC)CCCC)CCC>[C:17]([O:16][C@@H:14]([C@H:11]1[CH2:12][O:21][C:9](=[O:8])[N:10]1[CH2:30][C:29]1[CH:32]=[CH:33][C:26]([O:25][CH3:24])=[CH:27][CH:28]=1)[CH3:15])([CH3:18])([CH3:19])[CH3:20]
Reactant: C[C@@H](OC(C)(C)C)[C@@H](CO)NC(=O)OCc1ccccc1
Reactant: COc1ccc(CCl)cc1
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: [H-]
Agent: [I-]
Solvent: CCOC(C)=O
Solvent: CN(C)C=O
Product: COc1ccc(CN2C(=O)OC[C@@H]2[C@@H](C)OC(C)(C)C)cc1
Temperature: 0 °C
Reaction time: 0.5 h
Yield: 96.5 %

Procedure:
To a solution of benzyl((2R,3R)-3-(tert-butoxy)-1-hydroxybutan-2-yl)carbamate (5.88 g, 19.9 mmol) in 100 mL DMF was added NaH (60% in mineral oil, 1.62 g, 40.6 mmol) at 0° C. The reaction mixture was stirred for 30 min at 0° C. To the reaction mixture were added 4-methoxybenzyl chloride (4.07 mL, 29.9 mmol) and tetrabutylammonium iodide (0.74 g, 1.99 mmol) and the resulting mixture was warmed to room temperature and stirred for 15.5 h. The reaction mixture was poured into ice water (200 mL) forming a white suspension. EtOAc (100 mL) was added and the resulting mixture was stirred for 5 min to form a clear two layer solution. After separation, the aqueous phase was extracted with EtOAc (100 mL×3). The combined organic solution was washed with brine (80 mL), dried over Na2SO4, filtered and concentrated. Flash column chromatography (EtOAc/Heptane 0 to 70%) gave 5.90 g of (R)-4-((R)-1-(tert-butoxy)ethyl)-3-(4-methoxybenzyl)oxazolidin-2-one with minor impurities. Major product 1H NMR (400 MHz, MeOD) δ 7.38-7.29 (m, 2H), 6.99-6.93 (m, 2H), 4.68-4.58 (m, 1H), 4.33 (dd, J=9.3, 4.5 Hz, 1H), 4.27-4.17 (m, 2H), 3.89 (dd, J=6.4, 4.8 Hz, 1H), 3.81 (s, 3H), 3.65 (dd, J=9.0, 4.6 Hz, 1H), 1.09 (s, 9H), 1.02 (d, J=6.3 Hz, 3H). MS m/z 308.2 (M+H).
Reaction SMILES: [NH2:1][C:2]1[C:11]2[N:12]=[C:13]([CH2:37][CH2:38][CH2:39][CH3:40])[N:14]([CH2:15][CH2:16][CH2:17][N:18]([CH2:25][C:26]3[CH:27]=[C:28]([CH2:32][C:33]([O:35][CH3:36])=[O:34])[CH:29]=[CH:30][CH:31]=3)[CH2:19][CH2:20][CH2:21][N:22]([CH3:24])[CH3:23])[C:10]=2[C:9]2[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=2[N:3]=1.[CH3:41][N:42]1[CH2:47]CNC[CH2:43]1>>[NH2:1][C:2]1[C:11]2[N:12]=[C:13]([CH2:37][CH2:38][CH2:39][CH3:40])[N:14]([CH2:15][CH2:16][CH2:17][N:18]([CH2:25][C:26]3[CH:27]=[C:28]([CH2:32][C:33]([O:35][CH3:36])=[O:34])[CH:29]=[CH:30][CH:31]=3)[CH2:19][CH2:20][CH2:21][N:22]3[CH2:23][CH2:43][N:42]([CH3:47])[CH2:41][CH2:24]3)[C:10]=2[C:9]2[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=2[N:3]=1
Reactant: CN1CCNCC1
Reactant: CCCCc1nc2c(N)nc3ccccc3c2n1CCCN(CCCN(C)C)Cc1cccc(CC(=O)OC)c1
Product: CCCCc1nc2c(N)nc3ccccc3c2n1CCCN(CCCN1CCN(C)CC1)Cc1cccc(CC(=O)OC)c1

Procedure:
The title compound was prepared by the method of example 11step (x) using the product of example11 step (ix) (627 mg) and N-methylpiperazine (1 ml) as a colourless gum 120 mg.
Reaction SMILES: C[O:2][C:3]([C:5]1[S:6][C:7]([C:14](=[O:26])[NH:15][CH2:16][C:17]2[CH:25]=[CH:24][CH:23]=[C:22]3[C:18]=2[CH:19]=[CH:20][NH:21]3)=[CH:8][C:9]=1[C:10]([F:13])([F:12])[F:11])=[O:4].O.[OH-].[Li+].C1COCC1.Cl>O>[NH:21]1[C:22]2[C:18](=[C:17]([CH2:16][NH:15][C:14]([C:7]3[S:6][C:5]([C:3]([OH:4])=[O:2])=[C:9]([C:10]([F:12])([F:11])[F:13])[CH:8]=3)=[O:26])[CH:25]=[CH:24][CH:23]=2)[CH:19]=[CH:20]1
Reactant: COC(=O)c1sc(C(=O)NCc2cccc3[nH]ccc23)cc1C(F)(F)F
Agent: Cl
Agent: [Li+]
Agent: [OH-]
Solvent: C1CCOC1
Solvent: O
Product: O=C(NCc1cccc2[nH]ccc12)c1cc(C(F)(F)F)c(C(=O)O)s1

Procedure:
A mixture of 5-[(1H-Indol-4-ylmethyl)-carbamoyl]-3-trifluoromethyl-thiophene-2-carb oxylic acid methyl ester (270 mg, 0.33 mmol), lithium hydroxide monohydrate (300, mg, 7.10 mmol), THF (5 mL) and water (5 mL) was stirred 15 h, acidified with 1N HCl and extracted with EtOAc (×3). The organic extracts were combined, washed with brine, dried over sodium sulfate, filtered and evaporated to give the title compound, 260 mg (99%). MS m/e 369.0 (M+H+).
Reaction SMILES: [N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[CH2:7][OH:8].C(N(CC)CC)C.[S:16](Cl)([CH3:19])(=[O:18])=[O:17]>C1COCC1>[N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[CH2:7][O:8][S:16]([CH3:19])(=[O:18])=[O:17]
Reactant: CS(=O)(=O)Cl
Reactant: OCc1ccccn1
Solvent: C1CCOC1
Solvent: CCN(CC)CC
Product: CS(=O)(=O)OCc1ccccn1
Temperature: 25 °C
Reaction time: 2 h
Yield: 59.3 %

Procedure:
To a solution of 2-pyridylcarbinol (10) (300 mg, 2.70 mmol) and triethyl amine (698 mg, 6.75 mmol) in dry THF (10 mL) at 0° C. was added a solution of mesylchloride (470 mg, 4.1 mmol) in dry THF (10 mL). Reaction mixture was allowed to stir for 2 h at room temperature [reaction was followed by TLC]. Reaction mixture was concentrated to remove THF under reduced pressure and the residue was dissolved in CH2Cl2 (100 mL), washed with brine, dried over anhydrous Na2SO4 and concentrated under reduced pressure to give compound 11 (300 mg, 59%) as gum and it was taken as such for next step.
Reaction SMILES: [CH3:1][O:2][C:3](=[O:13])[CH:4]=[C:5]1[CH2:10][CH2:9][C:8]([CH3:12])([CH3:11])[CH2:7][CH2:6]1>C(OCC)(=O)C.CO.[Pd]>[CH3:1][O:2][C:3](=[O:13])[CH2:4][CH:5]1[CH2:10][CH2:9][C:8]([CH3:11])([CH3:12])[CH2:7][CH2:6]1
Reactant: COC(=O)C=C1CCC(C)(C)CC1
Agent: [Pd]
Solvent: CO
Solvent: CCOC(C)=O
Product: COC(=O)CC1CCC(C)(C)CC1
Yield: 80.4 %

Procedure:
To a stirred solution of the above alkene (100 mg, 0.54 mmol) in a mixture of ethyl acetate-methanol (0.8 mL, 1:1) was added Pd—C (10 mg, 20% on activated carbon) and the resultant mixture was stirred under hydrogen pressure (50 psi) for 2 h in a resealable glass pressure vessel equipped with a manometer and pressure valve. The catalyst was filtered off using a pad of Celite® and the Celite® pad was washed with an ethyl acetate-methanol mixture (1:1, about 10 mL). The combined filtrate was concentrated under reduced pressure to give the desired (4,4-dimethyl-cyclohexyl)-acetic acid methyl ester (80 mg).
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[CH:4][C:5]2[CH2:9][O:8][B:7]([OH:10])[C:6]=2[CH:11]=1.CN1CCOCC1.[CH3:19][O:20][CH2:21][CH2:22][C:23]1[CH:28]=[C:27]([N+:29]([O-:31])=[O:30])[CH:26]=[CH:25][C:24]=1[S:32](Cl)(=[O:34])=[O:33]>CC#N>[OH:10][B:7]1[C:6]2[CH:11]=[C:2]([NH:1][S:32]([C:24]3[CH:25]=[CH:26][C:27]([N+:29]([O-:31])=[O:30])=[CH:28][C:23]=3[CH2:22][CH2:21][O:20][CH3:19])(=[O:33])=[O:34])[CH:3]=[CH:4][C:5]=2[CH2:9][O:8]1
Reactant: Nc1ccc2c(c1)B(O)OC2
Reactant: COCCc1cc([N+](=O)[O-])ccc1S(=O)(=O)Cl
Solvent: CC#N
Solvent: CN1CCOCC1
Product: COCCc1cc([N+](=O)[O-])ccc1S(=O)(=O)Nc1ccc2c(c1)B(O)OC2
Temperature: 25 °C
Reaction time: 8 h
Yield: 65.4 %

Procedure:
To a solution of 6-amino-3H-benzo[c][1,2]oxaborol-1-ol (0.59 g, 3.9 mmol) and N-methylmorpholine (2.53 g, 25 mmol) in MeCN (70 mL) was added 2-(2-methoxyethyl)-4-nitrobenzene-1-sulfonyl chloride (1.4 g, 5 mmol) in MeCN (20 mL) at 0° C., then the solution was stirred at room temperature overnight. The mixture was concentrated in vacuo, and ethyl acetate and water was added to the residue. The organic layer was dried over Na2SO4 and concentrated to give the crude product. The crude product was purified by silica gel column chromatography (petroleum ether/ethyl acetate=10:1 to 0:1) to give N-(1-hydroxy-1,3-dihydrobenzo[c][1,2]oxaborol-6-yl)-2-(2-methoxyethyl)-4-nitrobenzene sulfonamide (1 g, yield 50%).