Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [C:1]1([NH2:8])[CH:6]=[CH:5][CH:4]=[C:3]([NH2:7])[CH:2]=1.O1CCCC1.C(N(CC)CC)C.[N+:21]([C:24]1[CH:25]=[C:26]([S:30](Cl)(=[O:32])=[O:31])[CH:27]=[CH:28][CH:29]=1)([O-:23])=[O:22]>O.CCOC(C)=O>[NH2:7][C:3]1[CH:2]=[C:1]([NH:8][S:30]([C:26]2[CH:27]=[CH:28][CH:29]=[C:24]([N+:21]([O-:23])=[O:22])[CH:25]=2)(=[O:31])=[O:32])[CH:6]=[CH:5][CH:4]=1
Reactant: O=[N+]([O-])c1cccc(S(=O)(=O)Cl)c1
Reactant: Nc1cccc(N)c1
Solvent: CCOC(C)=O
Solvent: CCN(CC)CC
Solvent: C1CCOC1
Product: Nc1cccc(NS(=O)(=O)c2cccc([N+](=O)[O-])c2)c1
Reaction time: 1 h
Yield: 88.8 %

Procedure:
Into a 1-neck round-bottom flask were added m-phenylenediamine (1.6 g, 14 mmol) and tetrahydrofuran (30 mL) and triethylamine (2.0 mL, 14 mmol). The mixture was cooled in ice bath and then m-nitrobenzenesulfonyl chloride (2.1 g, 9.6 mmol) was slowly added. The resultant mixture was warmed up to rt. after 1 h and EtOAc and water were then added. Aqueous layer was extracted again with EtOAc. The organics layers were combined, dried over Na2SO4 and the solvent was removed under vacuum. The crude was purified by silica gel column chromatography to give the desired product (2.5 g, 89%). LCMS for C12H11N3O4S (M+H)+: m/z=294.0. 1H NMR (300 MHz, CD3OD): δ 8.56 (t, J=2.0 Hz, 1H), 8.40 (ddd, J=8.2, 2.3, 1.2 Hz, 1H), 8.09 (ddd, J=7.8, 1.7, 1.0 HZ, 1H), 7.73 (t, J=8.1 Hz, 1H), 6.91 (t, J=8.1 Hz, 1H), 6.51 (t, J=2.2 Hz, 1H), 6.42 (ddd, J=8.1, 2.2, 1.0 Hz, 1H), 6.36 (ddd, J=7.9, 2.1, 1.0 Hz, 1H).
Reaction SMILES: CC1(C)C(C)(C)OB([C:9]2[CH:14]=[CH:13][C:12]([O:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH3:23])=[C:11]([C:24]([F:27])([F:26])[F:25])[CH:10]=2)O1.Br[C:30]1[CH:31]=[CH:32][C:33]([C:36]([NH:47][C:48]([O:50][C:51]([CH3:54])([CH3:53])[CH3:52])=[O:49])([C:42]([O:44][CH2:45][CH3:46])=[O:43])[C:37]([O:39][CH2:40][CH3:41])=[O:38])=[N:34][CH:35]=1.C([O-])([O-])=O.[Na+].[Na+]>C(O)C.O.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>[C:51]([O:50][C:48]([NH:47][C:36]([C:33]1[CH:32]=[CH:31][C:30]([C:9]2[CH:14]=[CH:13][C:12]([O:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH3:23])=[C:11]([C:24]([F:25])([F:26])[F:27])[CH:10]=2)=[CH:35][N:34]=1)([C:37]([O:39][CH2:40][CH3:41])=[O:38])[C:42]([O:44][CH2:45][CH3:46])=[O:43])=[O:49])([CH3:53])([CH3:54])[CH3:52]
Reactant: CCOC(=O)C(NC(=O)OC(C)(C)C)(C(=O)OCC)c1ccc(Br)cn1
Reactant: CCCCCCCCOc1ccc(B2OC(C)(C)C(C)(C)O2)cc1C(F)(F)F
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+]
Solvent: CCO
Solvent: O
Product: CCCCCCCCOc1ccc(-c2ccc(C(NC(=O)OC(C)(C)C)(C(=O)OCC)C(=O)OCC)nc2)cc1C(F)(F)F
Temperature: 80 °C

Procedure:
The suspension of 4,4,5,5-tetramethyl-2-(4-(octyloxy)-3-(trifluoromethyl)phenyl)-1,3,2-dioxaborolane 3a (136 mg, 0.34 mmol, 1.5 equiv), diethyl 2-(5-bromopyridin-2-yl)-2-(tert-butoxycarbonylamino)malonate (98 mg, 0.23 mmol, 1.0 equiv), Pd(PPh3)4 (26.3 mg, 0.023 mmol, 0.1 equiv), and Na2CO3 (120 mg, 1.14 mmol, 4.0 equiv) in ethanol-H2O was heated at 80° C. for 1 hour. The reaction mixture was filtered and the filtrate was purified by silica gel column to afford the title compound in 77% (110 mg) yield. MS (ESI, M+H+)=625.1; 1H NMR (400 MHz, CDCl3) δ 8.66 (s, 1H), 7.88 (s, 1H), 7.86 (dd, 1H, J=8.4 Hz, J=2.0 Hz), 7.75 (d, J=2.5 Hz), 7.66 (d, 1H, J=8.4 Hz), 7.08 (d, 1H, J=8.4 Hz), 6.82 (s, 1H), 4.30 (m, 4H), 4.09 (t, 2H, J=6.0 Hz), 1.84 (m, 2H), 1.46 (m, 11H), 1.28 (m, 14H), 0.90 (t, 3H, J=7.2 Hz).
Reaction SMILES: CC(C)([O-])C.[Na+].[CH2:7]([SH:15])[CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH3:14].[C:16]1([CH2:24]Cl)[CH:21]=[CH:20][C:19]([CH2:22][Cl:23])=[CH:18][CH:17]=1.Cl>CO>[CH2:7]([S:15][CH2:24][C:16]1[CH:21]=[CH:20][C:19]([CH2:22][Cl:23])=[CH:18][CH:17]=1)[CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH3:14]
Reactant: CCCCCCCCS
Reactant: ClCc1ccc(CCl)cc1
Agent: CC(C)(C)[O-]
Agent: Cl
Agent: [Na+]
Solvent: CO
Product: CCCCCCCCSCc1ccc(CCl)cc1
Reaction time: 0.5 h

Procedure:
1.83 g (19 mmol) of sodium t-butoxide and 2.78 g (19 mmol) of octanethiol were stirred into 40 g of methanol at room temperature. After 30 minutes, the clear solution was added in one portion to 3.33 g (19 mmol) of p-xylylene dichloride in 100 g of methanol. After one hour, the mixture was neutralized using 1N hydrochloric acid, and all the volatile components were removed under reduced pressure. The crude product was taken up in 250 ml of chloroform and washed twice with 100 ml of water each time, dried and evaporated under reduced pressure. 5.29 g, which, according to 1H-NMR-spectroscopy, consisted of 50% of product, 25% of starting material and 25% of p-bis(octylthiomethyl)benzene.
Reaction SMILES: ICI.[CH2:4]([C:8]1[CH2:13][CH:12]([CH3:14])[CH:11]([CH:15]([OH:17])[CH3:16])[CH2:10][CH:9]=1)[CH:5]([CH3:7])[CH3:6].[CH2:18]([Al](CC)CC)C.ClC1C=CC=C(C(OO)=O)C=1>CCCCCC.O>[CH2:4]([C:8]12[CH2:18][CH:9]1[CH2:10][CH:11]([CH:15]([OH:17])[CH3:16])[CH:12]([CH3:14])[CH2:13]2)[CH:5]([CH3:7])[CH3:6]
Reactant: CC(C)CC1=CCC(C(C)O)C(C)C1
Reactant: CC[Al](CC)CC
Agent: O=C(OO)c1cccc(Cl)c1
Solvent: CCCCCC
Solvent: ICI
Solvent: O
Product: CC(C)CC12CC(C)C(C(C)O)CC1C2
Reaction time: 16 h
Yield: 121.5 %

Procedure:
Diiodomethane (9.6 g, 36 mmol) was added at room temperature, with stirring and under nitrogen, to a solution of 1-(4-Isobutyl-6-methylcyclohex-3-enyl)ethanol 4b (3.5 g, 18 mmol) in hexane (50 ml). After cooling to 5° C. triethylaluminium (1M, 36 ml, 36 mmol) was added over 30 min while the temperature was kept below 5°. The reaction was allowed to return to room temperature and stirred for 16 h, then another portion of diiodomethane (9.6 g, 36 mmol) and triethylaluminium (1M, 36 ml, 36 mmol) were added. After a further 15 h yet more diiodomethane (4.8 g, 18 mmol) and triethylaluminium (1M, 18 ml, 18 mmol) were added. After 2 h stirring, the reaction being still incomplete, the reaction mixture was poured slowly, onto a stirred mixture of ice and water. The phases were separated and the aqueous one extracted twice with hexane. The combined organic layers were washed with water, twice with 2M HCl and again with water, dried (Na2SO4) and the solvent removed in vacuo. The crude oil (5.7 g) was dissolved in methylene chloride (50 ml) and solid 3-chloroperbenzoic acid (ca. 77%, 1.5 g, 6.7 mmol) was added in four portions under nitrogen. The mild exothermic effect was controlled with a cool water bath. The reaction was stirred till the unreacted 4b had been completely consumed (30 min). 2M NaOH was added and the mixture stirred until it became white. The phases were separated and the upper aqueous layer extracted twice with methylene chloride. The combined organic layers were washed twice with 2M NaOH and water, dried (MgSO4) and evaporated in vacuo to give 4.6 g of oil. The crude oil was purified by flash chromatography (MTBE/hex. 3:2) and combination of pure fractions gave 5b as a 1:1.1:1.8 mixture of diastereomers (3.4 g, 86% yield, colourless oil, 95% pure). Subsequent distillation provided an olfactory pure sample.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([CH2:9][CH:10]2[NH:19][CH2:18][CH2:17][C:16]3[C:11]2=[CH:12][C:13]([O:22][CH3:23])=[C:14]([O:20][CH3:21])[CH:15]=3)=[CH:5][C:4]=1[O:24][CH3:25].Cl.I[CH2:28][CH2:29][CH2:30][CH2:31][CH2:32][C:33]([S:46][C:47]1[CH:52]=[CH:51][C:50]([CH3:53])=[CH:49][CH:48]=1)([C:36]1[CH:41]=[CH:40][C:39]([O:42][CH3:43])=[C:38]([O:44][CH3:45])[CH:37]=1)[C:34]#[N:35]>>[CH3:45][O:44][C:38]1[CH:37]=[C:36]([C:33]([S:46][C:47]2[CH:48]=[CH:49][C:50]([CH3:53])=[CH:51][CH:52]=2)([CH2:32][CH2:31][CH2:30][CH2:29][CH2:28][N:19]2[CH2:18][CH2:17][C:16]3[C:11](=[CH:12][C:13]([O:22][CH3:23])=[C:14]([O:20][CH3:21])[CH:15]=3)[CH:10]2[CH2:9][C:6]2[CH:7]=[CH:8][C:3]([O:2][CH3:1])=[C:4]([O:24][CH3:25])[CH:5]=2)[C:34]#[N:35])[CH:41]=[CH:40][C:39]=1[O:42][CH3:43]
Reactant: COc1ccc(CC2NCCc3cc(OC)c(OC)cc32)cc1OC
Reactant: COc1ccc(C(C#N)(CCCCCI)Sc2ccc(C)cc2)cc1OC
Agent: Cl
Product: COc1ccc(CC2c3cc(OC)c(OC)cc3CCN2CCCCCC(C#N)(Sc2ccc(C)cc2)c2ccc(OC)c(OC)c2)cc1OC
Yield: 61.1 %

Procedure:
The procedure of Example 49 is repeated using 0.345 g of tetrahydropapaverine hydrochloride and 0.30 g of α-(5-iodopentyl)-3,4-dimethoxy-α-[(4-methylphenyl)thio]benzeneacetonitrile. This affords 0.263 g of the desired product as a yellow oil.
Reaction SMILES: [CH2:1]([C:5]1[N:9]([CH2:10][C:11]2[CH:16]=[CH:15][C:14]([C:17]3[C:18]([C:23]([O:25]C(C)(C)C)=[O:24])=[CH:19][CH:20]=[CH:21][CH:22]=3)=[CH:13][CH:12]=2)[C:8]2[CH:30]=[C:31]([N:34]([CH2:46][CH2:47][CH2:48][CH2:49][CH3:50])[CH2:35][CH2:36][CH2:37][CH2:38][NH:39][C:40]3[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=3)[CH:32]=[CH:33][C:7]=2[N:6]=1)[CH2:2][CH2:3][CH3:4].FC(F)(F)C(O)=O>C(Cl)Cl>[CH2:1]([C:5]1[N:9]([CH2:10][C:11]2[CH:12]=[CH:13][C:14]([C:17]3[C:18]([C:23]([OH:25])=[O:24])=[CH:19][CH:20]=[CH:21][CH:22]=3)=[CH:15][CH:16]=2)[C:8]2[CH:30]=[C:31]([N:34]([CH2:46][CH2:47][CH2:48][CH2:49][CH3:50])[CH2:35][CH2:36][CH2:37][CH2:38][NH:39][C:40]3[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=3)[CH:32]=[CH:33][C:7]=2[N:6]=1)[CH2:2][CH2:3][CH3:4]
Reactant: CCCCCN(CCCCNc1ccccc1)c1ccc2nc(CCCC)n(Cc3ccc(-c4ccccc4C(=O)OC(C)(C)C)cc3)c2c1
Solvent: O=C(O)C(F)(F)F
Solvent: ClCCl
Product: CCCCCN(CCCCNc1ccccc1)c1ccc2nc(CCCC)n(Cc3ccc(-c4ccccc4C(=O)O)cc3)c2c1

Procedure:
Prepared in analogous manner to Example 9 from tert.butyl 4'-[(2-n-butyl-6-(N-(4-phenylamino-n-butyl)-n-pentylamino)-benzimidazol-1-yl)-methyl]biphenyl-2-carboxylate and trifluoroacetic acid in methylene chloride.
Reaction SMILES: [CH3:1][NH:2][CH3:3].[C:4](=[S:6])=[S:5]>>[CH3:1][N:2]([CH3:4])[C:3](=[S:6])[S:5][S:5][C:4](=[S:6])[N:2]([CH3:3])[CH3:1]
Reactant: CNC
Reactant: S=C=S
Product: CN(C)C(=S)SSC(=S)N(C)C
Reaction time: 0.82 h

Procedure:
The work was carried out as in Example 3, but now the rate of addition of carbon disulfide corresponded to the rate at which dimethylamine was released during the reaction. No further carbon disulfide was added after 46 minutes and the reaction had ended after 49 minutes. This method yielded a total of 35.85 g of tetramethyl thiuram disulfide, corresponding to 99.6% of theoretical.
Reaction SMILES: [ClH:1].CO[NH2:4].[F:5][C:6]([F:21])([F:20])[C:7]1[CH:8]=[C:9]([C:17](=O)[CH3:18])[CH:10]=[C:11]([C:13]([F:16])([F:15])[F:14])[CH:12]=1.C([O-])(=O)C.[Na+].[O-]S([O-])(=O)=O.[Mg+2].Cl>C(O)C.O>[ClH:1].[CH3:18][CH:17]([C:9]1[CH:8]=[C:7]([C:6]([F:21])([F:20])[F:5])[CH:12]=[C:11]([C:13]([F:16])([F:15])[F:14])[CH:10]=1)[NH2:4]
Reactant: CON
Reactant: CC(=O)c1cc(C(F)(F)F)cc(C(F)(F)F)c1
Agent: CC(=O)[O-]
Agent: Cl
Agent: O=S(=O)([O-])[O-]
Solvent: O
Solvent: CCO
Product: CC(N)c1cc(C(F)(F)F)cc(C(F)(F)F)c1
Temperature: 0 °C
Yield: 84.2 %

Procedure:
O-Methylhydroxylamine hydrochloride (19.57 g, 234 mmol) was added to a solution of 1-[3,5-bis(trifluoromethyl)phenyl]ethanone (50 g, 195 mmol), and sodium acetate (31.9 g, 234 mmol) in ethanol (450 mL) and water (150 mL) and the mixture was heated under reflux for 18 hours. The mixture was cooled, water (1000 mL) was added and the mixture was extracted with diethyl ether. The combined organic fractions were dried (MgSO4) and the solvent was evaporated under reduced pressure. The residue was dissolved in tetrahydrofuran (100 mL), cooled to 0° C. and borane-tetrahydrofuran complex (1M in tetrahydrofuran, 730 mL) was added. The mixture was heated under reflux for 18 hours, cooled and hydrochloric acid (5M, 500 mL) was added slowly. The tetrahydrofuran was evaporated under reduced pressure and the mixture was basified with aqueous sodium hydroxide (4M). The mixture was extracted with ether and the combined organic fractions were washed with aqueous sodium hydroxide (4M) and dried (MgSO4), and ethereal hydrogen chloride (400 mL, 400 mmol) was added. The solid was collected, washing with diethyl ether, and dried in vacuo to give (RS)-α-methyl-3,5-bis(trifluoromethyl)benzenemethanamine hydrochloride as a colorless solid (48.2 g, 100%). 1H NMR (400 MHz, CD3OD) δ 8.13 (2H, s), 8.07 (1H, s), 4.73 (1H, q, J 6.8 Hz), 3.31 (2H, d, J 1.4 Hz), and 1.69 (3H, d, J 6.8 Hz). m/z (ES+) 258 (M+1). A sample was suspended in aqueous sodium hydroxide (4M) and extracted with ether. The combined organic fractions were washed with aqueous sodium hydroxide (4M), dried (MgSO4) and the solvent was evaporated under reduced pressure to give the title compound as a colorless oil. 1H NMR (400 MHz, CDCl3) δ 7.85 (2H, s), 7.76 (1H, s), 4.30 (1H, q, J 6.6 Hz), 1.74 (2H, br s), and 1.42 (3H, d, J 6.6 Hz). m/z (ES+) 258 (M+1).
Reaction SMILES: [CH3:1][S:2]([C:5]1[C:13]([S:14]([CH3:17])(=[O:16])=[O:15])=[CH:12][C:8]([C:9](Cl)=[O:10])=[C:7]([CH3:18])[CH:6]=1)(=[O:4])=[O:3].[NH2:19][C:20]([NH2:22])=[NH:21].O>CN(C=O)C>[CH3:1][S:2]([C:5]1[C:13]([S:14]([CH3:17])(=[O:16])=[O:15])=[CH:12][C:8]([C:9]([NH:21][C:20]([NH2:22])=[NH:19])=[O:10])=[C:7]([CH3:18])[CH:6]=1)(=[O:4])=[O:3]
Reactant: Cc1cc(S(C)(=O)=O)c(S(C)(=O)=O)cc1C(=O)Cl
Reactant: N=C(N)N
Solvent: O
Solvent: CN(C)C=O
Product: Cc1cc(S(C)(=O)=O)c(S(C)(=O)=O)cc1C(=O)NC(=N)N
Reaction time: 5 h
Yield: 64.8 %

Procedure:
A solution of 4,5-bismethanesulfonyl-2-methylbenzoyl chloride, prepared as described in 2.1., in 5 l of DMF is added dropwise at 12° to the guanidine solution prepared as described in 2.2. The reaction mixture is stirred at 20° for 5 hours, and 45 l of cold water (0-50) are added slowly. The deposited crystals are filtered off and rinsed with ice-water, acetonitrile and diethyl ether. The crude crystals are dissolved in 315 l of hot acetonitrile/water (20:1). The solution is treated with 200 g of activated carbon, filtered and cooled to 0°, giving N-(4,5-bismethanesulfonyl-2-methylbenzoyl)guanidine as the acetonitrile adduct in a yield of 64.8%; m.p. 233-2340 °.
Reaction SMILES: Br[C:2]1[CH:12]=[CH:11][CH:10]=[CH:9][C:3]=1[C:4]([O:6][CH2:7][CH3:8])=[O:5].[CH2:13]=[CH:14][C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1.C(N(CC)CC)C>C(#N)C.C([O-])(=O)C.C([O-])(=O)C.[Pd+2].C1(C)C=CC=CC=1P(C1C=CC=CC=1C)C1C=CC=CC=1C>[C:15]1(/[CH:14]=[CH:13]/[C:2]2[CH:12]=[CH:11][CH:10]=[CH:9][C:3]=2[C:4]([O:6][CH2:7][CH3:8])=[O:5])[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1
Reactant: C=Cc1ccccc1
Reactant: CCOC(=O)c1ccccc1Br
Agent: [Pd+2]
Agent: CC(=O)[O-]
Agent: Cc1ccccc1P(c1ccccc1C)c1ccccc1C
Solvent: CC#N
Solvent: CCN(CC)CC
Product: CCOC(=O)c1ccccc1/C=C/c1ccccc1
Yield: 103.9 %

Procedure:
8.9 g (38.9 mmol) of ethyl 2-bromobenzoate, 5.1 g (49.4 mmol) of styrene, 0.18 g (0.8 mmol) of palladium diacetate, 0.48 g (1.6 mmol) of tri-o-tolylphosphine and 5 g (49.1 mmol) of triethylamine were reacted in 90 ml of anhydrous acetonitrile at 100° C. for 23 h. The mixture was then filtered and the filtrate was diluted with ethyl acetate, washed with water, dried and concentrated under reduced pressure. 10.2 g (100%) of the product were obtained.
Reaction SMILES: C1(C)C=CC(S([O-])(=O)=O)=CC=1.[NH+]1C=CC=CC=1.[Cl:18][C:19]1[C:38]([Cl:39])=[CH:37][C:22]2[N:23]([CH:26]3[CH2:36][CH2:35][CH:29]4[O:30]C(C)(C)[O:32][CH:28]4[CH2:27]3)[CH:24]=[N:25][C:21]=2[CH:20]=1>CO>[Cl:18][C:19]1[C:38]([Cl:39])=[CH:37][C:22]2[N:23]([C@@H:26]3[CH2:36][CH2:35][C@@H:29]([OH:30])[C@@H:28]([OH:32])[CH2:27]3)[CH:24]=[N:25][C:21]=2[CH:20]=1
Reactant: CC1(C)OC2CCC(n3cnc4cc(Cl)c(Cl)cc43)CC2O1
Agent: Cc1ccc(S(=O)(=O)[O-])cc1
Agent: c1cc[nH+]cc1
Solvent: CO
Product: O[C@@H]1CC[C@@H](n2cnc3cc(Cl)c(Cl)cc32)C[C@@H]1O
Yield: 45 %

Procedure:
Pyridinium para-toluenesulfonate (33.6 mg, 134.7 mmol) was added to (±)-5,6-dichloro-1-(2,2dimethyl-hexahydro-benzo[1,3]dioxol-5-yl)-1H-benzimidazole (part d of this experiment, 459.6 mg, 1.35 mmol) in methanol (7 ml) and the reaction was heated at reflux for 19 hr and concentrated. The residue was purified by column chromatography eluting with methanol:ethyl acetate (1:9) to give the title compound (184.4 mg, 45%). Rf=0.19 (1:9 methanol:ethyl acetate); 1H-NMR (CD3OD, 300 MHz) δ8.36 (s, 1H), 7.91 (s, 1H), 7.80 (s, 1H), 4.70 (tt, 1H, J=12, 4), 4.11 (d, 1H, J=3), 3.79-3.73 (m, 1H), 2.26 (dq, 1H, J=13, 3), 2.15-2.10 (m, 2H), 2.06-1.99 (m, 2H), 1.88-1.85 (m, 1H); MS (ES) M+H=301.
Reaction SMILES: B(F)(F)F.CSC.[C:8]([C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=1[C:17]1[CH:22]=[CH:21][C:20]([C:23]2[CH:24]=[N:25][N:26]([CH2:37][C:38]#[N:39])[C:27]=2[C:28]2[CH:33]=[C:32]([CH3:34])[CH:31]=[C:30]([O:35]C)[CH:29]=2)=[CH:19][N:18]=1)(=[O:10])[CH3:9]>ClCCl>[C:8]([C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=1[C:17]1[CH:22]=[CH:21][C:20]([C:23]2[CH:24]=[N:25][N:26]([CH2:37][C:38]#[N:39])[C:27]=2[C:28]2[CH:33]=[C:32]([CH3:34])[CH:31]=[C:30]([OH:35])[CH:29]=2)=[CH:19][N:18]=1)(=[O:10])[CH3:9]
Reactant: COc1cc(C)cc(-c2c(-c3ccc(-c4ccccc4C(C)=O)nc3)cnn2CC#N)c1
Agent: FB(F)F
Solvent: CSC
Solvent: ClCCl
Product: CC(=O)c1ccccc1-c1ccc(-c2cnn(CC#N)c2-c2cc(C)cc(O)c2)cn1
Reaction time: 24 h

Procedure:
Borontrifluoride-dimethylsulfide (0.13 mL, 1.2 mmol) was dropwise added to a solution of the methoxy compound (50.7 mg, 0.12 mmol) prepared in Example 70 in dichloromethane (4 mL) at room temperature under nitrogen atmosphere, and stirred for 24 hours. The reaction mixture was concentrated by vacuum distillation. The residue was treated in ethyl acetate (100 mL) and brine (50 mL), and the organic layer was dried over anhydrous magnesium sulfate and distilled under vacuum. Purification through column chromatography (silica gel, ethyl acetate) afforded pure hydroxy products (30 mg, 62%).
Reaction SMILES: [C:1]1([NH:7]N)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[F:9][C:10]1[CH:18]=[C:17]2[C:13]([CH2:14][CH2:15][C:16]2=O)=[CH:12][CH:11]=1>C(O)C.C(O)(=O)C>[F:9][C:10]1[CH:18]=[C:17]2[C:13]([CH2:14][C:15]3[C:2]4[CH:3]=[CH:4][CH:5]=[CH:6][C:1]=4[NH:7][C:16]=32)=[CH:12][CH:11]=1
Reactant: NNc1ccccc1
Reactant: O=C1CCc2ccc(F)cc21
Solvent: CC(=O)O
Solvent: CCO
Product: Fc1ccc2c(c1)-c1[nH]c3ccccc3c1C2
Temperature: 85 °C

Procedure:
To a solution of phenyl hydrazine (1.32 mL, 13.32 mmol) and 6-fluoro-1-indanone (2.02 g, 13.46 mmol) in ethanol (7.6 mL) was added glacial acetic acid (3 drops). The solution was stirred at reflux (85° C.) for 17 minutes and cooled to room temperature. Upon cooling, white crystals precipitated out of solution. These crystals were collected by vacuum filtration and dissolved in isopropanol (23 mL) Sulfuric acid (36N, 1.51 mL) was added via syringe and the resulting solution was stirred at reflux (90° C.) for 18 hours and subsequently cooled to room temperature. The solution was then basified to pH 10 via addition of aqueous sodium hydroxide (2% by mass) resulting in the formation of precipitate. The solid was collected by vacuum filtration to yield 37b as a brown solid in 46% crude yield (1.38 g, 6.17 mmol). Crude product was brought on to the next step without further purification. For purposes of characterization, the product was purified by flash column chromatography (20:1 to 20:1.5 hexanes-ethyl acetate). 1H NMR (600 MHz, CDCl3): δ 8.26 (s, 1H), 7.64-7.65 (d, 1H, J=7.8 Hz), 7.42-7.44 (m, 2H), 7.20-7.23 (td, 1H, J=7.2, 1.2 Hz), 7.16-7.19 (td, J=7.2, 1.2 Hz) 7.12-7.14 (dd, 1H, J=8.4, 2.4 Hz), 6.88-6.91 (m, 1H), 3.68 (s, 1H); 13C NMR (150 MHz, CDCl3): δ 161.5-163.1 (d, J=242 Hz), 142.9 (d, J=2.4 Hz), 142.3 (d, J=2.9 Hz), 140.7, 136.5 (d, J=9.6 Hz), 126.0 (d, J=9.0 Hz), 124.5, 123.9, 122.3, 120.4, 119.2, 112.2, 111.0 (d, J=22.7 HZ), 104.8 (d, J=24.3 Hz), 29.8; FTIR: cm−1 3398, 1589, 1528, 1462, 1268, 1187, 744, 665. ESI-HRMS: Calcd. for C15H10FN+ [M]+: 223.0792, found 223.0792.
Reaction SMILES: [CH2:1]([NH2:21])/[CH:2]=[C:3](/[CH2:5][CH2:6][CH2:7][C@@H:8]([CH2:10][CH2:11][CH2:12][C@@H:13]([CH2:15][CH2:16][CH2:17][CH:18]([CH3:20])[CH3:19])[CH3:14])[CH3:9])\[CH3:4].C1(=O)OC(=O)CC1>N1C=CC=CC=1>[CH2:1]([NH2:21])[CH2:2][CH:3]([CH2:5][CH2:6][CH2:7][CH:8]([CH2:10][CH2:11][CH2:12][CH:13]([CH2:15][CH2:16][CH2:17][CH:18]([CH3:20])[CH3:19])[CH3:14])[CH3:9])[CH3:4]
Reactant: C/C(=C\CN)CCC[C@H](C)CCC[C@H](C)CCCC(C)C
Agent: O=C1CCC(=O)O1
Solvent: c1ccncc1
Product: CC(C)CCCC(C)CCCC(C)CCCC(C)CCN
Yield: 52.7 %

Procedure:
Phytylamine (2.32 g), succinic anhydride (1.16 g) and pyridine (10 ml) was stirred at room temperature for 48 hours. Most of the pyridine was removed under reduced pressure and the crude product dissolved in dichloromethane and washed with 2M HCl (2×100 ml). The organic was layer separated, dried (MgSO4) and concentrated in vacuo to dryness. The crude product was chromotographed (ethyl acetate as eluant) to give phytanamine hemisuccinamide 1.23 g (91%) as a thick liquid which solidified on standing 1H-n.m.r. (CDCl3) δ0.8-1.8 (m, 39H), 2.5 (m, 2H, CH2COO—), 2.6 (m, 2H, CH2COOH), 3.2 (m, 2H, CH2N—), 5.79 (b, 1H, NH), m/z (CI, CH4), 412 (M+)
Reaction SMILES: [C:1]1([C:7]2[N:8]=[CH:9][N:10]([C:12]([C:25]3[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=3)([C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=3)[C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=3)[CH:11]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[Li]CCCC.[Si:36]([O:43][C:44]1[C:45]([F:55])=[C:46]([CH:49]=[C:50]([O:52][CH2:53][CH3:54])[CH:51]=1)[CH:47]=[O:48])([C:39]([CH3:42])([CH3:41])[CH3:40])([CH3:38])[CH3:37].[NH4+].[Cl-]>C1COCC1.CCOC(C)=O>[Si:36]([O:43][C:44]1[C:45]([F:55])=[C:46]([CH:47]([C:9]2[N:10]([C:12]([C:25]3[CH:26]=[CH:27][CH:28]=[CH:29][CH:30]=3)([C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=3)[C:19]3[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=3)[CH:11]=[C:7]([C:1]3[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=3)[N:8]=2)[OH:48])[CH:49]=[C:50]([O:52][CH2:53][CH3:54])[CH:51]=1)([C:39]([CH3:40])([CH3:42])[CH3:41])([CH3:38])[CH3:37]
Reactant: CCOc1cc(C=O)c(F)c(O[Si](C)(C)C(C)(C)C)c1
Reactant: c1ccc(-c2cn(C(c3ccccc3)(c3ccccc3)c3ccccc3)cn2)cc1
Agent: [Cl-]
Agent: [Li]CCCC
Agent: [NH4+]
Solvent: CCOC(C)=O
Solvent: C1CCOC1
Product: CCOc1cc(O[Si](C)(C)C(C)(C)C)c(F)c(C(O)c2nc(-c3ccccc3)cn2C(c2ccccc2)(c2ccccc2)c2ccccc2)c1
Temperature: 0 °C
Reaction time: 0.5 h
Yield: 84.6 %

Procedure:
To a solution of intermediate 8.1 (1.00 g, 2.59 mmol) in 20 mL THF at 0° C., was added BuLi (1.4 M, 2.03 mL, 2.85 mmol). The mixture was stirred for 30 min at 0° C., then a solution of 3-(tert-butyldimethylsilyloxy)-5-ethoxy-2-fluorobenzaldehyde (773 mg, 2.59 mmol) in 2 mL THF was added dropwise. The mixture was stirred at 0° C. for 30 min, quenced with sat. NH4Cl and diluted with EtOAc. The organic phase was washed with H2O and brine, dried (Na2SO4) and concentrated. The crude product was purified by flash chromatography (0 to 30% EtOAc/hexanes, gradient) to afford 1.50 g (80%) of Intermediate 123.1 as a pale yellow solid.
Reaction SMILES: OC[C:3]1[N:4]=CN[C:7]=1[CH2:8]SCCN.CSC(SC)=C[N+]([O-])=O.[N+:22]([CH:25]=[C:26](SC)[NH:27][CH2:28][CH2:29][S:30][CH2:31][C:32]1[NH:36][CH:35]=[N:34][C:33]=1[CH2:37][OH:38])([O-:24])=[O:23].C(N)C#C>>[N+:22]([CH:25]=[C:26]([NH:4][CH2:3][C:7]#[CH:8])[NH:27][CH2:28][CH2:29][S:30][CH2:31][C:32]1[NH:36][CH:35]=[N:34][C:33]=1[CH2:37][OH:38])([O-:24])=[O:23]
Reactant: CSC(=C[N+](=O)[O-])NCCSCc1[nH]cnc1CO
Reactant: NCCSCc1[nH]cnc1CO
Agent: C#CCN
Agent: CSC(=C[N+](=O)[O-])SC
Product: C#CCNC(=C[N+](=O)[O-])NCCSCc1[nH]cnc1CO

Procedure:
When 2-[(4-hydroxymethyl-1H-imidazol-5-yl)methylthio]-ethylamine [prepared according to the procedure described in Belgian Pat. No. 843,840] is reacted with 1,1-bis(methylthio)-2-nitroethylene according to the procedure of Example 6, Step A, and the resultant 1-nitro-2-methylthio-2-{2-[(4-hydroxymethyl-1H-imidazol-5-yl)methylthio]ethylamino}ethylene is treated with propargylamine by the procedure of Example 6, Step B, the title compound is produced.