Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: O1CC1COC1C=CC=C2C=1CCCC2=O.Cl.[CH2:18]1[C:27]2[C:22](=[CH:23][CH:24]=[CH:25][CH:26]=2)[CH2:21][CH2:20][CH:19]1[NH:28]CC(O)COC1C=CC=C2C=1CCCC2=O>C(O)C>[NH2:28][CH:19]1[CH2:20][CH2:21][C:22]2[C:27](=[CH:26][CH:25]=[CH:24][CH:23]=2)[CH2:18]1
Reactant: O=C1CCCc2c(OCC(O)CNC3CCc4ccccc4C3)cccc21
Agent: Cl
Agent: O=C1CCCc2c(OCC3CO3)cccc21
Solvent: CCO
Product: NC1CCc2ccccc2C1

Procedure:
Following the procedure of Example 27, but starting from 5-(2,3-epoxypropoxy)-1-oxotetralin (20.2 g), prepared as described in BE 739,195, and 2-aminotetralin (14.81 g) in absolute ethanol (130 ml), N-(1,2,3,4-tetrahydronaphth-2-yl)-2-hydroxy-3-(1-oxo-1,2,3,4-tetrahydronaphth-5-yloxy)propanamine hydrochloride is obtained ((iA), R=H, E and G, taken together form a group --CH2 --CH2 --CH2 --CO--, and the chain is attached to position 2 of the tetralin moiety).
Reaction SMILES: [C:1]([O:5][C:6]([NH:8][C:9]1[CH:10]=[C:11]([CH:15]=[C:16]([NH:18][C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])[CH:17]=1)[C:12](O)=[O:13])=[O:7])([CH3:4])([CH3:3])[CH3:2].O>C1COCC1>[C:1]([O:5][C:6]([NH:8][C:9]1[CH:10]=[C:11]([CH2:12][OH:13])[CH:15]=[C:16]([NH:18][C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])[CH:17]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2]
Reactant: CC(C)(C)OC(=O)Nc1cc(NC(=O)OC(C)(C)C)cc(C(=O)O)c1
Solvent: O
Solvent: C1CCOC1
Product: CC(C)(C)OC(=O)Nc1cc(CO)cc(NC(=O)OC(C)(C)C)c1
Temperature: 25 °C
Reaction time: 5 h
Yield: 56 %

Procedure:
A 2.00 g (5.68 mmol) portion of 3,5-di-(tert-butoxycarbonylamino)benzoic acid was dissolved in 15 ml of THF, 3.77 ml (39.7 mmol) of borane-methyl sulfide complex dissolved in 10 ml of THF was added dropwise to the thus prepared solution, and the mixture was stirred at room temperature for 5 hours. The reaction solution was cooled to 0° C., mixed with water and extracted with ethyl acetate. The ethyl acetate layer was washed with saturated brine and dried with anhydrous sodium sulfate, and then the solvent was evaporated under reduced pressure. The resulting residue was purified by silica gel column chromatography (chloroform/methanol=20/1) to obtain 1.08 g (yield, 56%) of 1,3-di-tert-butoxycarbonylamino-5-hydroxymethylbenzene.
Reaction SMILES: O1[C:5]2([CH2:10][CH2:9][C:8](=[O:11])[CH2:7][CH2:6]2)OCC1.[NH:12]1[CH2:15][CH:14]([NH:16][C:17](=[O:34])[CH2:18][NH:19][C:20]2[C:29]3[C:24](=[CH:25][CH:26]=[C:27]([C:30]([F:33])([F:32])[F:31])[CH:28]=3)[N:23]=[CH:22][N:21]=2)[CH2:13]1.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+]>>[O:11]=[C:8]1[CH2:7][CH2:6][CH:5]([N:12]2[CH2:13][CH:14]([NH:16][C:17](=[O:34])[CH2:18][NH:19][C:20]3[C:29]4[C:24](=[CH:25][CH:26]=[C:27]([C:30]([F:31])([F:33])[F:32])[CH:28]=4)[N:23]=[CH:22][N:21]=3)[CH2:15]2)[CH2:10][CH2:9]1
Reactant: O=C(CNc1ncnc2ccc(C(F)(F)F)cc12)NC1CNC1
Reactant: O=C1CCC2(CC1)OCCO2
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: [Na+]
Product: O=C1CCC(N2CC(NC(=O)CNc3ncnc4ccc(C(F)(F)F)cc34)C2)CC1

Procedure:
Reaction of 1,4-dioxaspiro[4.5]decan-8-one with N-(azetidin-3-yl)-2-((6-(trifluoromethyl)quinazolin-4-yl)amino)acetamide (as prepared in Example 1 Step G) in the presence of TEA and NaBH(OAc)3 as described in Example 1, Step H followed by acidic deprotection of the ketal afforded the product.
Reaction SMILES: N12CCCN=C1CCCCC2.Cl.[NH2:13][CH2:14][C:15]1[CH:23]=[CH:22][CH:21]=[C:20]2[C:16]=1[C:17](=[O:33])[N:18]([CH:25]1[CH2:30][CH2:29][C:28](=[O:31])[NH:27][C:26]1=[O:32])[C:19]2=[O:24].[C:34]([O:37][CH2:38][C:39](Cl)=[O:40])(=[O:36])[CH3:35]>CC#N>[C:34]([O:37][CH2:38][C:39](=[O:40])[NH:13][CH2:14][C:15]1[CH:23]=[CH:22][CH:21]=[C:20]2[C:16]=1[C:17](=[O:33])[N:18]([CH:25]1[CH2:30][CH2:29][C:28](=[O:31])[NH:27][C:26]1=[O:32])[C:19]2=[O:24])(=[O:36])[CH3:35]
Reactant: CC(=O)OCC(=O)Cl
Reactant: NCc1cccc2c1C(=O)N(C1CCC(=O)NC1=O)C2=O
Agent: Cl
Solvent: C1CCC2=NCCCN2CC1
Solvent: CC#N
Product: CC(=O)OCC(=O)NCc1cccc2c1C(=O)N(C1CCC(=O)NC1=O)C2=O
Reaction time: 0.33 h
Yield: 75.4 %

Procedure:
1,8-Diazabicyclo[5,4,0]undec-7-ene (0.62 g, 4.08 mmol) was added to a stirred suspension of 4 (aminomethyl)-2-(2,6-dioxo(3-piperidyl))isoindoline-1,3-dione hydrochloride (0.600 g, 1.85 mmol) in CH3CN (50 ml). After stirring for 20 min, acetoxyacetyl chloride (0.28 g, 2.03 mmol) was added. The mixture was stirred at room temperature for 17 hours. The solvent was removed in vacuo and the residue was dissolved in CH2Cl2 (70 ml). The CH2Cl2 solution was washed with 1N HCl (30 ml), H2O (30 ml), brine (30 ml) and dried (MgSO4). The solvent was removed in vacuo and the residue was purified by chromatography (SiO2, CH2Cl2:CH3OH 100:2.5) to give (N-{[2-(2,6-dioxo(3-piperidyl))-1,3-dioxoisoindolin-4-yl]methyl}carbamoyl)methyl acetate (0.54 g, 75%) as a white solid: mp 108–110° C.; 1H NMR (DMSO-d6) δ d 11.14 (s, 1H), 8.68 (t, J=6.0 Hz, 1H), 7.87–7.79 (m, 2H), 7.71–7.65 (m, 1H), 5.19–5.12 (dd, J=5.3 and 12.4 Hz, 1H), 4.77 (d, J=5.9 Hz, 2H), 4.56 (s, 2H), 2.96–2.83 (m, 1H), 2.63–2.47 (m, 2H), 2.11 (s, 3H), 2.08–1.98 (m, 1H); 13C NMR (DMSO-d6) δ d 172.66, 169.96, 169.72, 167.46, 167.37, 166.36, 138.80, 134.68, 133.01, 132.47, 127.04, 121.87, 62.36, 48.84, 37.46, 30.38, 21.93, 20.49; Anal. Calcd. For C18H17N3O7+0.15H2O: C, 55.43; H, 4.47; N, 10.77. Found: C, 55.43; H, 4.54; N, 10.44.
Reaction SMILES: FC(F)(F)C(O)=O.[Cl:8][C:9]1[CH:14]=[C:13]2[NH:15][C:16](=[O:38])[C:17]3([CH:21]([C:22]4[CH:27]=[CH:26][CH:25]=[C:24]([Cl:28])[C:23]=4[F:29])[CH:20]([C:30]([OH:32])=O)[NH:19][CH:18]3[CH2:33][C:34]([CH3:37])([CH3:36])[CH3:35])[C:12]2=[CH:11][CH:10]=1.C(N(C(C)C)CC)(C)C.C1(P(Cl)(C2C=CC=CC=2)=O)C=CC=CC=1.[F:63][C:64]1[CH:70]=[C:69]([S:71]([CH3:74])(=[O:73])=[O:72])[CH:68]=[CH:67][C:65]=1[NH2:66]>>[F:63][C:64]1[CH:70]=[C:69]([S:71]([CH3:74])(=[O:72])=[O:73])[CH:68]=[CH:67][C:65]=1[NH:66][C:30]([CH:20]1[NH:19][CH:18]([CH2:33][C:34]([CH3:36])([CH3:35])[CH3:37])[C:17]2([C:12]3[C:13](=[CH:14][C:9]([Cl:8])=[CH:10][CH:11]=3)[NH:15][C:16]2=[O:38])[CH:21]1[C:22]1[CH:27]=[CH:26][CH:25]=[C:24]([Cl:28])[C:23]=1[F:29])=[O:32]
Reactant: CS(=O)(=O)c1ccc(N)c(F)c1
Reactant: CC(C)(C)CC1NC(C(=O)O)C(c2cccc(Cl)c2F)C12C(=O)Nc1cc(Cl)ccc12
Agent: O=P(Cl)(c1ccccc1)c1ccccc1
Solvent: CCN(C(C)C)C(C)C
Solvent: O=C(O)C(F)(F)F
Product: CC(C)(C)CC1NC(C(=O)Nc2ccc(S(C)(=O)=O)cc2F)C(c2cccc(Cl)c2F)C12C(=O)Nc1cc(Cl)ccc12

Procedure:
In a manner similar to the method described in Example 27, rac-(2′S,3′R,4′S,5′R)-6-chloro-4′-(3-chloro-2-fluoro-phenyl)-2′-(2,2-dimethyl-propyl)-2-oxo-1,2-dihydro-spiro[indole-3,3′-pyrrolidine]-5′-carboxylic acid trifluoroacetic acid prepared in Example 4 (0.36 g, 0.62 mmol), was reacted with diisopropylethylamine (0.64 g, 5 mmol), diphenylphosphinic chloride (0.59 g, 2.5 mmol), then reacted with 2-fluoro-4-(methylsulfonyl)aniline (Matrix) (0.12 g, 0.62 mmol) at 80° C. to give rac-(2′S,3′R,4′S,5′R)-6-chloro-4′-(3-chloro-2-fluoro-phenyl)-2′-(2,2-dimethyl-propyl)-2-oxo-1,2-dihydro-spiro[indole-3,3′-pyrrolidine]-5′-carboxylic acid (2-fluoro-4-methanesulfonyl-phenyl)-amide as a off white solid (Yield 20 mg, 5%).
Reaction SMILES: [Cl:1][C:2]1[C:7](Cl)=[N:6][CH:5]=[CH:4][N:3]=1.[NH2:9][NH2:10]>C(O)C>[Cl:1][C:2]1[C:7]([NH:9][NH2:10])=[N:6][CH:5]=[CH:4][N:3]=1
Reactant: Clc1nccnc1Cl
Reactant: NN
Solvent: CCO
Product: NNc1nccnc1Cl
Yield: 75.6 %

Procedure:
2,3-Dichloropyrazine (2 mL, 13 mmol) was dissolved in 95% ethanol (4 mL) and to this was added, dropwise and with stirring, hydrazine anhydrous (2 mL, 67 mmol). During the addition of the hydrazine the solution became warm and yellowish. Following cooling of this mixture in an ice bath, the resulting material was isolated by filtration, washed with cold aqueous 95% ethanol to riled 1-(3-chloropyrazin-2-yl)hydrazine (1.42 g, 73% yield) as white crystals. No further purification was done. MS m/z: 145.0 (M+1).
Reaction SMILES: [NH2:1][C:2]1[C:6]([C:7]2[C:12]([Cl:13])=[CH:11][CH:10]=[CH:9][C:8]=2[Cl:14])=[N:5][S:4][N:3]=1.C(N(CC)CC)C.[C:22](Cl)(=[O:26])[CH:23]([CH3:25])[CH3:24].O>CN(C)C=O>[C:22]([NH:1][C:2]1[C:6]([C:7]2[C:12]([Cl:13])=[CH:11][CH:10]=[CH:9][C:8]=2[Cl:14])=[N:5][S:4][N:3]=1)(=[O:26])[CH:23]([CH3:25])[CH3:24]
Reactant: Nc1nsnc1-c1c(Cl)cccc1Cl
Reactant: CC(C)C(=O)Cl
Solvent: CCN(CC)CC
Solvent: O
Solvent: CN(C)C=O
Product: CC(C)C(=O)Nc1nsnc1-c1c(Cl)cccc1Cl
Temperature: 60 °C
Yield: 36.5 %

Procedure:
To a solution of 0.49 g of 3-amino-4-(2,6-dichlorophenyl)-1,2,5-thiadiazole and 0.22 g of triethylamine in N,N-dimethylformamide, 0.27 g of isobutyryl chloride was added and the mixture was heated at 60° C. for 12 hours. After allowing to cool, the mixture was poured into water and was extracted with ether. The ether layer was washed twice with dilute hydrochloric acid, twice with water and twice with saturated aqueous sodium chloride solution. The resultant was dried over anhydrous sodium sulfate, concentrated and purified by silica gel column chromatography to obtain 0.23 g of 3-isobutyrylamino-4-(2,6-dichlorophenyl)-1,2,5-thiadiazole
Reaction SMILES: [Cl:1][CH2:2][C:3]1[O:4][CH:5]=[C:6]([C:8]([O:10]C)=[O:9])[N:7]=1.[OH-].[Li+]>C1COCC1.CO.O>[Cl:1][CH2:2][C:3]1[O:4][CH:5]=[C:6]([C:8]([OH:10])=[O:9])[N:7]=1
Reactant: COC(=O)c1coc(CCl)n1
Agent: [Li+]
Agent: [OH-]
Solvent: O
Solvent: C1CCOC1
Solvent: CO
Product: O=C(O)c1coc(CCl)n1
Temperature: 25 °C
Reaction time: 1 h
Yield: 94 %

Procedure:
Methyl 2-(chloromethyl)-1,3-oxazole-4-carboxylate (1.0 g, 5.70 mmol) was dissolved in THF/methanol mixture (9:1) and 1M lithium hydroxide (11.39 ml, 11.39 mmol) was added slowly. The reaction mixture was stirred at RT for 1 h, diluted with water and pH was adjusted to 2. The reaction mixture was extracted three times with ethyl acetate. Ethyl acetate phases were combined, dried and evaporated to dryness to yield the title compound (94%). 1H-NMR (400 MHz; DMSO3): δ 4.93 (s, 2H), 8.80 (s, 1H), 13.20 (bs, 1H).
Reaction SMILES: C1(C=CC(O)=CC=1)O.C1(C=CC=C(O)C=1)O.[OH:17][C:18]1[CH:23]=[CH:22][C:21]([C:24]([C:29]2[CH:34]=[CH:33][C:32]([OH:35])=[CH:31][CH:30]=2)([CH2:26]CC)[CH3:25])=[CH:20][CH:19]=1>>[OH:17][C:18]1[CH:19]=[CH:20][C:21]([C:24]([C:29]2[CH:30]=[CH:31][C:32]([OH:35])=[CH:33][CH:34]=2)([CH3:26])[CH3:25])=[CH:22][CH:23]=1
Reactant: CCCC(C)(c1ccc(O)cc1)c1ccc(O)cc1
Agent: Oc1ccc(O)cc1
Agent: Oc1cccc(O)c1
Product: CC(C)(c1ccc(O)cc1)c1ccc(O)cc1

Procedure:
hydroquinone; resorcinol; 2,2-bis-(4-hydroxy phenyl)pentane;
Reaction SMILES: C[C:2]1[CH:3]=[CH:4][C:5]([N:11]2[N:15]=[CH:14][CH:13]=[N:12]2)=[C:6]([CH:10]=1)[C:7]([OH:9])=[O:8].[F:16]C1C=CC(C(O)=O)=C(I)C=1.N1C=CN=N1>>[F:16][C:3]1[CH:2]=[CH:10][C:6]([C:7]([OH:9])=[O:8])=[C:5]([N:11]2[N:15]=[CH:14][CH:13]=[N:12]2)[CH:4]=1
Reactant: Cc1ccc(-n2nccn2)c(C(=O)O)c1
Reactant: O=C(O)c1ccc(F)cc1I
Agent: c1c[nH]nn1
Product: O=C(O)c1ccc(F)cc1-n1nccn1

Procedure:
The title compound was prepared following the same general protocol as described for 5-methyl-2-(2H-1,2,3-triazol-2-yl)benzoic acid in Example A11 using 4-fluoro-2-iodobenzoic acid and 1,2,3-triazole. ESI-MS (m/z): 208.2 [M+1]+.
Reaction SMILES: [OH:1][CH:2]1[CH2:5][N:4]([C:6]2[S:7][CH:8]=[C:9]([C:11](=[O:19])[NH:12][C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=3)[N:10]=2)[CH2:3]1.[CH3:20][S:21](Cl)(=[O:23])=[O:22].C(N(CC)CC)C>C(Cl)Cl>[CH3:20][S:21]([O:1][CH:2]1[CH2:3][N:4]([C:6]2[S:7][CH:8]=[C:9]([C:11](=[O:19])[NH:12][C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=3)[N:10]=2)[CH2:5]1)(=[O:23])=[O:22]
Reactant: CS(=O)(=O)Cl
Reactant: O=C(Nc1ccccc1)c1csc(N2CC(O)C2)n1
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: CS(=O)(=O)OC1CN(c2nc(C(=O)Nc3ccccc3)cs2)C1
Temperature: 0 °C
Yield: 89.7 %

Procedure:
To a solution of 3-hydroxy-1-(4-phenylcarbamoyl-1,3-thiazol-2-yl)azetidine (1.18 g, 4.29 mmol) (obtained as described in Reference Example 32(2)) in methylene chloride (60 ml) were added methanesulfonyl chloride (0.50 ml, 6.44 mmol) and triethylamine (0.90 ml, 6.44 mmol) in an ice bath, and then the mixture was stirred in the ice bath for 2 hours. After checking the completion of the reaction, the reaction mixture was partitioned between ethyl acetate and saturated aqueous sodium hydrogencarbonate solution. The organic layer was washed with saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The residue was purified by chromatography on a silica gel column using methylene chloride:ethyl acetate (9:1) as the eluant to afford 3-methanesulfonyloxy-1-(4-phenylcarbamoyl-1,3-thiazol-2-yl)azetidine (1.36 g, yield 89%) as a pale yellow solid.
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]([CH:22]=[CH:23][CH:24]=1)[O:5][C:6]1[CH:15]=[C:14]2[C:9]([C:10]([OH:21])=[C:11]([C:17]([O:19][CH3:20])=[O:18])[N:12]=[C:13]2I)=[CH:8][CH:7]=1.[C:25]([Cu])#[N:26].C(Cl)Cl>CN(C=O)C>[C:25]([C:13]1[C:14]2[C:9](=[CH:8][CH:7]=[C:6]([O:5][C:4]3[CH:22]=[CH:23][CH:24]=[C:2]([F:1])[CH:3]=3)[CH:15]=2)[C:10]([OH:21])=[C:11]([C:17]([O:19][CH3:20])=[O:18])[N:12]=1)#[N:26]
Reactant: COC(=O)c1nc(I)c2cc(Oc3cccc(F)c3)ccc2c1O
Reactant: N#C[Cu]
Solvent: CN(C)C=O
Solvent: ClCCl
Product: COC(=O)c1nc(C#N)c2cc(Oc3cccc(F)c3)ccc2c1O
Temperature: 120 °C
Reaction time: 0.17 h

Procedure:
Methyl 7-(3-fluorophenoxy)-4-hydroxy-1-iodoisoquinoline-3-carboxylate (100 mg, 0.23 mmol) and CuCN (41 mg, 0.46 mmol) were suspended in DMF (1.0 mL). The resulting mixture was heated at 120° C. for 7 minutes and then cooled to room temperature. The reaction crude was poured into CH2Cl2 (30 mL) and stirred vigorously for 10 minutes at room temperature. The resulting suspension was filtered through a pad of celite and the filtrate was washed with H2O and brine sequentially. The organic layer was dried over MgSO4, concentrated, and purified by flash chromatography (0-50% EtOAc/hexanes) to give the title compound in 67 mg. MS: (−) m/z 337.25 (M−1).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[CH:5][CH:6]=[C:7]2[C:11]=1[N:10]([CH:12]([C:16]1[CH:17]=[N:18][CH:19]=[CH:20][CH:21]=1)[CH2:13][CH2:14]O)[CH:9]=[CH:8]2.[CH2:22]([N:24](CC)CC)C.CS(Cl)(=O)=O>ClCCl>[CH3:1][O:2][C:3]1[CH:4]=[CH:5][CH:6]=[C:7]2[C:11]=1[N:10]([CH:12]([C:16]1[CH:17]=[N:18][CH:19]=[CH:20][CH:21]=1)[CH2:13][CH2:14][NH:24][CH3:22])[CH:9]=[CH:8]2
Reactant: COc1cccc2ccn(C(CCO)c3cccnc3)c12
Reactant: CCN(CC)CC
Agent: CS(=O)(=O)Cl
Solvent: ClCCl
Product: CNCCC(c1cccnc1)n1ccc2cccc(OC)c21
Reaction time: 0.5 h

Procedure:
To a solution of 3-(7-methoxy-indol-1-yl)-3-pyridin-3-yl-propan-1-ol in dichloromethane (10 ml) was added triethylamine (0.086 g) followed by methanesulfonyl chloride (0.071 g) dropwise at 0° C. The mixture was stirred for 30 minutes at the same temperature and then the reaction was quenched by partitioning between water and dichloromethane. The organic layer was washed with bicarbonate solution, dried and evaporated to dryness. The crude product was taken up in an ethanolic solution of methyl amine (33%, 4 ml), stirred for 30 minutes at room temperature and then at 100° C. in a microwave reactor. After cooling, the solvents were removed, the crude product was partitioned between dichloromethane and bicarbonate solution, and the organic layer separated. The resulting residue was purified by chromatography on silica gel eluting with mixtures of dichloromethane, methanol and ammonium hydroxide to give 0.088 g of [3-(7-methoxy-indol-1-yl)-3-pyridin-3-yl-propyl]-methyl-amine.
Reaction SMILES: [CH2:1]([C:3]1[N:13]([CH2:14][C:15]2[CH:16]=[C:17]([CH:35]=[CH:36][CH:37]=2)[C:18]([C:20]2[CH:34]=[CH:33][C:23]([CH2:24][O:25][Si](C(C)(C)C)(C)C)=[CH:22][CH:21]=2)=[O:19])[C:6]2=[N:7][C:8]([CH3:12])=[CH:9][C:10]([CH3:11])=[C:5]2[N:4]=1)[CH3:2].CCCC[N+](CCCC)(CCCC)CCCC.[F-].C1COCC1>C1COCC1.C(OCC)(=O)C>[CH2:1]([C:3]1[N:13]([CH2:14][C:15]2[CH:16]=[C:17]([CH:35]=[CH:36][CH:37]=2)[C:18]([C:20]2[CH:21]=[CH:22][C:23]([CH2:24][OH:25])=[CH:33][CH:34]=2)=[O:19])[C:6]2=[N:7][C:8]([CH3:12])=[CH:9][C:10]([CH3:11])=[C:5]2[N:4]=1)[CH3:2]
Reactant: CCc1nc2c(C)cc(C)nc2n1Cc1cccc(C(=O)c2ccc(CO[Si](C)(C)C(C)(C)C)cc2)c1
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: [F-]
Solvent: C1CCOC1
Solvent: CCOC(C)=O
Product: CCc1nc2c(C)cc(C)nc2n1Cc1cccc(C(=O)c2ccc(CO)cc2)c1
Temperature: 25 °C
Reaction time: 2 h
Yield: 82.8 %

Procedure:
{4-[3-(2-Ethyl-5,7-dimethylimidazo[4,5-b]pyridin-3-ylmethyl)benzoyl]benzyloxy)-tert-butyldimethylsilane (0.898 g, 1.75 mmol) obtained in Step 4 was dissolved in THF (15 mL), and a 1.0 mol/L TBAF-THF solution (5.24 mL, 5.24 mmol) was added to the solution, followed by stirring at room temperature for 2 hours. The reaction mixture was diluted with ethyl acetate, and washed with water and saturated brine. The organic layer was dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate:hexane=2:1), followed by crystallization from ethanol to obtain Compound 14 (0.579 g, yield 83%).
Reaction SMILES: C(Cl)Cl.[Cl:4][C:5]1[CH:10]=[CH:9][C:8]([S:11]([CH:14]([C:21]2[CH:26]=[C:25]([F:27])[CH:24]=[CH:23][C:22]=2[F:28])[C:15]2[CH:16]=[N:17][CH:18]=[CH:19][CH:20]=2)(=[O:13])=[O:12])=[CH:7][CH:6]=1.ClC1C=CC=C(C(OO)=[O:37])C=1.C(OCC)(=O)C>CCOCC>[Cl:4][C:5]1[CH:10]=[CH:9][C:8]([S:11]([CH:14]([C:21]2[CH:26]=[C:25]([F:27])[CH:24]=[CH:23][C:22]=2[F:28])[C:15]2[CH:16]=[N+:17]([O-:37])[CH:18]=[CH:19][CH:20]=2)(=[O:12])=[O:13])=[CH:7][CH:6]=1
Reactant: O=C(OO)c1cccc(Cl)c1
Reactant: O=S(=O)(c1ccc(Cl)cc1)C(c1cccnc1)c1cc(F)ccc1F
Solvent: CCOC(C)=O
Solvent: CCOCC
Solvent: ClCCl
Product: O=S(=O)(c1ccc(Cl)cc1)C(c1ccc[n+]([O-])c1)c1cc(F)ccc1F
Reaction time: 24 h
Yield: 40.2 %

Procedure:
To methylene chloride (15 ml) of the 3-[(4-chlorophenylsulfonyl)-(2,5-difluorophenyl)methyl]pyridine (162 mg, 0.427 mmol) obtained in Example 19 was added 3-chloroperbenzoic acid (81 mg, 0.47 mmol). The resulting mixture was stirred for 24 hours. The reaction mixture was diluted with ether (60 ml). The diluted mixture was washed with a saturated aqueous solution of sodium bicarbonate, water and brine, dried and filtered. The filtrate was concentrated under reduced pressure to give a residue. The resulting residue was subjected to silica gel chromatography (ethyl acetate) to give the title compound (68 mg, 40%). The compound was crystallized from ethanol to afford colorless needle crystals.
Reaction SMILES: [C:1]([C:5]1[CH:6]=[C:7]([C:16]([CH3:19])([CH3:18])[CH3:17])[C:8]2[O:13][CH:12]=[CH:11][C:10](=[O:14])[C:9]=2[CH:15]=1)([CH3:4])([CH3:3])[CH3:2]>CCOC(C)=O.[Pd]>[C:1]([C:5]1[CH:15]=[C:9]2[C:8](=[C:7]([C:16]([CH3:19])([CH3:18])[CH3:17])[CH:6]=1)[O:13][CH2:12][CH2:11][C:10]2=[O:14])([CH3:4])([CH3:3])[CH3:2]
Reactant: CC(C)(C)c1cc(C(C)(C)C)c2occc(=O)c2c1
Agent: [Pd]
Solvent: CCOC(C)=O
Product: CC(C)(C)c1cc2c(c(C(C)(C)C)c1)OCCC2=O
Temperature: 25 °C
Reaction time: 2 h
Yield: 85 %

Procedure:
To 1.0 g (3.87 mmol) of 4H-6,8-di-t-butyl-benzopyran-4-one in 8 mL of EtOAc was added 200 mg of 10% Pd/C. The mixture was degassed, followed by addition of H2 gas and stirred under an H2 gas atmosphere for 2 h at RT. After filtration (celite), the product was concentrated and purified (SiO2 chromatography, 5% EtOAc-hexanes) to give 857 mg (3.29 mmol) of 32 as a white solid (85% yield): TLC (5% EtOAc-hex) Rf 0.7; 1H-NMR (CDCl3) δ1.32 (s, 9H, CH3), 1.42 (s, 9H, CH3), 2.78 (t, J=6.0 Hz, 2H, CH2), 4.52 (t, J=6.0 Hz, 2H, CH2), 7.53 (d, J=2.4 Hz, 1H, Ar-H), 7.81 (d, J=2.4 Hz, 1H, Ar-H)
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][C:10]=1[NH2:11])[NH:7][C:6](=[O:12])[C:5]2([CH3:14])[CH3:13].[N:15]1[CH:20]=[CH:19][C:18]([CH2:21][C:22](OC)=O)=[CH:17][CH:16]=1>>[OH2:12].[CH3:13][C:5]1([CH3:14])[C:4]2[C:8](=[CH:9][C:10]3[NH:11][C:22]([CH2:21][C:18]4[CH:19]=[CH:20][N:15]=[CH:16][CH:17]=4)=[N:1][C:2]=3[CH:3]=2)[NH:7][C:6]1=[O:12]
Reactant: COC(=O)Cc1ccncc1
Reactant: CC1(C)C(=O)Nc2cc(N)c(N)cc21
Product: CC1(C)C(=O)Nc2cc3[nH]c(Cc4ccncc4)nc3cc21
Product: O

Procedure:
A suspension of 7.3 g. (0.038 mol) 5,6-diamino-3,3-dimethylindolin-2-one in 11.6 g. (0.077 mol) methyl 4-pyridylacetate is heated, while stirring, under an atmosphere of nitrogen for about 16 hours to 180° C. Subsequently, excess ester is distilled off in a vacuum and the residue obtained is separated on silica gel (elution agent: dichloromethane/ammonia-saturated methanol 20:1 v/v). Yield: 1.8 g. (16% of theory); m.p. 333°-337° C. (recrystallised from water/methanol 10:1 v/v).
Reaction SMILES: [CH3:1][C:2]12[C:9]([CH3:11])([CH3:10])[CH:6]([CH2:7][CH2:8]1)[CH2:5][CH:4](O)[O:3]2.[I-].[C:14]1([P+](C2C=CC=CC=2)(C2C=CC=CC=2)C(C)C)[CH:19]=CC=C[CH:15]=1>>[CH3:1][C@@:2]1([OH:3])[CH2:8][CH2:7][C@@H:6]([CH2:5][CH:4]=[C:14]([CH3:19])[CH3:15])[C:9]1([CH3:11])[CH3:10]
Reactant: CC12CCC(CC(O)O1)C2(C)C
Reactant: CC(C)[P+](c1ccccc1)(c1ccccc1)c1ccccc1
Agent: [I-]
Product: CC(C)=CC[C@@H]1CC[C@@](C)(O)C1(C)C
Yield: 71.1 %

Procedure:
Using the procedure of Example 7, 5 g of 1,8,8-trimethyl-2-oxa bicyclo [3,2,1] octan-3-ol and 15 g of triphenyl isopropyl phosphonium iodide were reacted and the product was chromatographed over silica gel and was eluted with an 8-2 cyclohexane-ethyl acetate mixture to obtain 4.1 g of (1R,S) 1,2,2-trimethyl-3-(3-methyl-2-butenyl)-cyclopentanol.
Reaction SMILES: [CH2:1]([NH:5][C:6]1[C:14]([S:15](=[O:18])(=[O:17])[NH2:16])=[CH:13][C:9]([C:10]([OH:12])=[O:11])=[CH:8][C:7]=1[N+:19]([O-])=O)[CH2:2][CH2:3][CH3:4].[OH-].[Na+].[H][H]>O>[NH2:19][C:7]1[CH:8]=[C:9]([CH:13]=[C:14]([S:15](=[O:18])(=[O:17])[NH2:16])[C:6]=1[NH:5][CH2:1][CH2:2][CH2:3][CH3:4])[C:10]([OH:12])=[O:11]
Reactant: [H][H]
Reactant: CCCCNc1c([N+](=O)[O-])cc(C(=O)O)cc1S(N)(=O)=O
Agent: [Na+]
Agent: [OH-]
Solvent: O
Product: CCCCNc1c(N)cc(C(=O)O)cc1S(N)(=O)=O

Procedure:
A suspension of 4-butylamino-3-nitro-5-sulphamyl-benzoic acid (8.6 g) in water (175 ml) was adjusted to pH 9.5 by addition of 2N sodium hydroxide. The resulting solution was hydrogenated after addition of Pd-on-carbon catalyst (0.5 g catalyst containing 10% Pd). After the hydrogen uptake had become negligible, the catalyst was removed by filtration, and the 3-amino-4-butylamino-5-sulphamyl-benzoic acid was precipitated from the filtrate by addition of 4N hydrochloric acid until pH 3. After recrystallization from aqueous methanol the melting point was 211-211.5°C.
Reaction SMILES: [F-].C([N+](CCCC)(CCCC)CCCC)CCC.[CH3:19][N:20]([CH2:22][C:23]1C[C:26]([C:28]2[CH:35]=[CH:34][CH:33]=[CH:32][C:29]=2[CH:30]=[O:31])=[CH:25][CH:24]=1)[CH3:21].[F:36][C:37]([Si](C)(C)C)([F:39])[F:38].Cl.C1C[O:48]CC1>>[CH3:21][N:20]([CH2:22][C:23]1[O:48][C:26]([C:28]2[CH:35]=[CH:34][CH:33]=[CH:32][C:29]=2[CH:30]([OH:31])[C:37]([F:39])([F:38])[F:36])=[CH:25][CH:24]=1)[CH3:19]
Reactant: CN(C)CC1=CC=C(c2ccccc2C=O)C1
Reactant: C[Si](C)(C)C(F)(F)F
Reactant: C1CCOC1
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: Cl
Agent: [F-]
Product: CN(C)Cc1ccc(-c2ccccc2C(O)C(F)(F)F)o1
Temperature: 25 °C
Reaction time: 4 h
Yield: 66 %

Procedure:
Tetrabutylammonium fluoride (0.013 ml; 1.0 M solution in tetrahydrofuran) was added to a solution of 2-(4-dimethylaminomethyl-cyclopenta-1,3-dienyl)-benzaldehyde (287 mg, 1.25) and trifluoromethyltrimethylsilane (TMSCF3) (222 μl, 1.5 mmol) in 5 ml THF at 0° C. The formed mixture was warmed up to room temperature and stirred at room temperature for 4 hours. The reaction mixture was then treated with 5 ml of 1N HCl and stirred at room temperature overnight. The product was extracted with ethyl acetate (3×50 ml). The organic layer was separated and dried over sodium sulfate. The organic solvent was evaporated to give 250 mg of 1-[2-(5-dimethylaminomethyl-furan-2-yl)-phenyl]-2,2,2-trifluoro-ethanol, yield 66%.