Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [C:1]([O:5][C:6]([NH:8][CH2:9][CH2:10][NH2:11])=[O:7])([CH3:4])([CH3:3])[CH3:2].C1CN([P+](ON2N=NC3C=CC=CC2=3)(N2CCCC2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F.[CH:45]([Si:48]([CH:66]([CH3:68])[CH3:67])([CH:63]([CH3:65])[CH3:64])[O:49][C:50]1[CH:59]=[C:58]2[C:53]([CH:54]=[CH:55][CH:56]=[C:57]2[C:60](O)=[O:61])=[CH:52][CH:51]=1)([CH3:47])[CH3:46].C(N(CC)C(C)C)(C)C>C1COCC1>[C:1]([O:5][C:6]([NH:8][CH2:9][CH2:10][NH:11][C:60]([C:57]1[C:58]2[C:53](=[CH:52][CH:51]=[C:50]([O:49][Si:48]([CH:63]([CH3:65])[CH3:64])([CH:66]([CH3:68])[CH3:67])[CH:45]([CH3:46])[CH3:47])[CH:59]=2)[CH:54]=[CH:55][CH:56]=1)=[O:61])=[O:7])([CH3:4])([CH3:3])[CH3:2]
Reactant: CC(C)[Si](Oc1ccc2cccc(C(=O)O)c2c1)(C(C)C)C(C)C
Reactant: CC(C)(C)OC(=O)NCCN
Agent: F[P-](F)(F)(F)(F)F
Agent: c1ccc2c(c1)nnn2O[P+](N1CCCC1)(N1CCCC1)N1CCCC1
Solvent: C1CCOC1
Solvent: CCN(C(C)C)C(C)C
Product: CC(C)[Si](Oc1ccc2cccc(C(=O)NCCNC(=O)OC(C)(C)C)c2c1)(C(C)C)C(C)C
Reaction time: 4 h

Procedure:
To 2-(tert-butoxycarbonylamino)ethylamine (70 mg, 0.44 mmol) in dry THF (1 mL) under argon were added PYBOP (226 g, 0.43 mmol), 7-(triisopropylsilyloxy)-1-naphthoic acid, as described above in Step D, (148 mg, 0.43 mmol), and N,N-diisopropylethylamine (0.115 mL, 0.66 mmol). The reaction mixture was stirred for 4 hrs, then partitioned between CH2Cl2 (50 mL) and saturated aqueous NaHCO3 (20 mL). The organic layer was dried over Na2SO4, filtered, and concentrated in vacuo. The residue was purified by flash column chromatography on silica, eluting with a gradient of CH2Cl2 −10% to 15% EtOAc to yield the desired product as a white solid.
Reaction SMILES: [C:1]([O:5][C:6]([N:8]1[CH2:12][C@H:11]([F:13])[C@@H:10]([O:14][Si:15]([C:18]([CH3:21])([CH3:20])[CH3:19])([CH3:17])[CH3:16])[C@H:9]1[C:22]([OH:24])=O)=[O:7])([CH3:4])([CH3:3])[CH3:2].[Cl:25][C:26]1[C:27]([F:36])=[C:28]([C:32]2([NH2:35])[CH2:34][CH2:33]2)[CH:29]=[CH:30][CH:31]=1.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>CN(C=O)C>[C:1]([O:5][C:6]([N:8]1[CH2:12][C@H:11]([F:13])[C@@H:10]([O:14][Si:15]([C:18]([CH3:19])([CH3:20])[CH3:21])([CH3:16])[CH3:17])[C@H:9]1[C:22](=[O:24])[NH:35][C:32]1([C:28]2[CH:29]=[CH:30][CH:31]=[C:26]([Cl:25])[C:27]=2[F:36])[CH2:33][CH2:34]1)=[O:7])([CH3:3])([CH3:4])[CH3:2]
Reactant: CC(C)(C)OC(=O)N1C[C@H](F)[C@@H](O[Si](C)(C)C(C)(C)C)[C@H]1C(=O)O
Reactant: NC1(c2cccc(Cl)c2F)CC1
Agent: CN(C)C(On1nnc2ccccc21)=[N+](C)C
Agent: F[P-](F)(F)(F)(F)F
Solvent: CCN(C(C)C)C(C)C
Solvent: CN(C)C=O
Product: CC(C)(C)OC(=O)N1C[C@H](F)[C@@H](O[Si](C)(C)C(C)(C)C)[C@H]1C(=O)NC1(c2cccc(Cl)c2F)CC1
Temperature: 25 °C
Reaction time: 2 h

Procedure:
To a solution of (2S,3S,4S)-3-(tert-butyl-dimethyl-silanyloxy)-4-fluoro-pyrrolidine-1,2-dicarboxylic acid 1-tert-butyl ester (300 mg, 0.825 mmol), 1-(3-chloro-2-fluoro-phenyl)-cyclopropylamine (prepared as described in Part C, 272 mg, 0.908 mmol) and HBTU (376 mg, 0.99 mmol) in DMF (10 mL) was added DIPEA (0.432 ml, 2.476 mmol) under nitrogen atmosphere. The reaction mixture was stirred 2 h at 25° C. Then quenched by addition of a saturated aqueous solution of NaHCO3 and extracted with EtOAc (×2). The combined organic extracts were dried (Na2SO4), filtered and concentrated. The crude residue was purified by flash column chromatography on silica gel (c-hexane/EtOAc 1:1). MS (UPLC): 531.5/533.5 [M+H]+, 505.5 [M+NH4]+, 510.4 [M+Na]+; tR (UPLC conditions m): 1.55 min.
Reaction SMILES: [CH2:1]([NH:17][C:18]1[CH:30]=[CH:29][C:21]([C:22]([O:24][CH2:25][CH:26]2[O:28][CH2:27]2)=[O:23])=[CH:20][CH:19]=1)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH3:16].S(=O)(=O)(O)[OH:32].COCCOC>O>[CH2:1]([NH:17][C:18]1[CH:30]=[CH:29][C:21]([C:22]([O:24][CH2:25][CH:26]([OH:28])[CH2:27][OH:32])=[O:23])=[CH:20][CH:19]=1)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH3:16]
Reactant: CCCCCCCCCCCCCCCCNc1ccc(C(=O)OCC2CO2)cc1
Reactant: O=S(=O)(O)O
Solvent: O
Solvent: COCCOC
Product: CCCCCCCCCCCCCCCCNc1ccc(C(=O)OCC(O)CO)cc1

Procedure:
A mixture of 100 mg of 2,3-epoxypropyl 4-(n-hexadecylamino)benzoate, 0.2 ml of 1N sulfuric acid, and 1.0 ml of 1,2-dimethoxyethane is heated under reflux for one hour, diluted with water, and filtered to yield 2,3-dihydroxypropyl 4-(n-hexadecylamino)benzoate as a white solid, mp 112° C.
Reaction SMILES: [CH2:1]=[CH:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.[CH3:9][SiH:10]([CH3:14])[O:11][CH2:12][CH3:13]>[Pt].C1(C)C=CC=CC=1>[CH2:1]([Si:10]([CH3:14])([CH3:9])[O:11][CH2:12][CH3:13])[CH2:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1
Reactant: C=Cc1ccccc1
Reactant: CCO[SiH](C)C
Agent: [Pt]
Solvent: Cc1ccccc1
Product: CCO[Si](C)(C)CCc1ccccc1
Temperature: 41 °C
Yield: 27 %

Procedure:
Comparative Example 1. (Reaction between Styrene and Dimethylethoxysilane) A glass tube was filled with 312 mg of styrene and 312 mg of dimethylethoxysilane. The contents were combined with 1 μL of a toluene solution of a complex of divinylsiloxane and 0-valence platinum (platinum content: 0.4 Wt. %). The tube was sealed with Teflon tape and was heated for 30 minutes in an oil bath at 41° C. After cooling, the product was subjected to GC analysis. The analyses confirmed that the conversion of styrene was 36% and that phenethyldimethylethoxysilane was produced at a yield of 27%. The yield of (α-methylbenzyl)dimethylethoxysilane was 8.5%.
Reaction SMILES: [NH2:1][C:2]1[N:6]([CH:7]([CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH3:16])[CH2:8][CH2:9][CH3:10])[N:5]=[C:4]([CH3:17])[C:3]=1[C:18]([NH2:20])=[O:19].[CH2:21]1[O:29][C:28]2[CH:27]=[CH:26][C:25]([CH2:30][C:31](OC)=O)=[CH:24][C:23]=2[O:22]1.[O-]CC.[Na+].C(=O)([O-])O.[Na+]>ClCCl>[CH2:21]1[O:29][C:28]2[CH:27]=[CH:26][C:25]([CH2:30][C:31]3[NH:20][C:18](=[O:19])[C:3]4[C:4]([CH3:17])=[N:5][N:6]([CH:7]([CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH3:16])[CH2:8][CH2:9][CH3:10])[C:2]=4[N:1]=3)=[CH:24][C:23]=2[O:22]1
Reactant: COC(=O)Cc1ccc2c(c1)OCO2
Reactant: CCCCCCC(CCC)n1nc(C)c(C(N)=O)c1N
Agent: CC[O-]
Agent: O=C([O-])O
Agent: [Na+]
Solvent: ClCCl
Product: CCCCCCC(CCC)n1nc(C)c2c(=O)[nH]c(Cc3ccc4c(c3)OCO4)nc21
Yield: 60.6 %

Procedure:
6 mg (0.021 mmol) of 5-amino-3-methyl-1-(4-decyl)-1H-pyrazole-4-carboxamide and 20 mg (0.103 mmol) of methyl 3,4-methylenedioxyphenylacetate are refluxed for 6 hours in 0.3 ml of a 0.5M ethanolic sodium ethoxide solution. After dichloromethane and saturated aqueous sodium hydrogen carbonate solution have been added, the phases are separated. Purification by chromatography gives 5.4 mg (59%) of a solid, Rf=0.60 (dichloromethane/methanol=15:1).
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)[C:5]([NH2:8])=[CH:6][CH:7]=1.[CH:16](O)=O>>[Br:1][C:2]1[CH:7]=[CH:6][C:5]2[N:8]=[CH:16][N:9]([C:10]3[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=3)[C:4]=2[CH:3]=1
Reactant: Nc1ccc(Br)cc1Nc1ccccc1
Reactant: O=CO
Product: Brc1ccc2ncn(-c3ccccc3)c2c1
Temperature: 25 °C
Reaction time: 2 h
Yield: 81.9 %

Procedure:
To a stirred mixture of 4-bromo-N2-phenyl-benzene-1,2-diamine (step A) (420 mg, 1.6 mmol) and trimethyl orthoformiate (4.8 g, 5 ml, 45.2 mmol), formic acid (1.2 g, 1 ml, 26.1 mmol) was added at room temperature, and afterwards the reaction mixture was allowed to stir at for 2 h under reflux conditions. The reaction mixture was cooled to room temperature, evaporated and extracted with ethyl acetate (2×40 ml). The combined organic layers were washed with sat. sodium bicarbonate solution (20 ml) and brine (20 ml), dried (MgSO4) and evaporated. The crude product (400 mg) was purified by flash chromatography on silica gel (heptane/ethyl acetate 3:2) to yield the title compound as an off-white solid (358 mg, 82%), MS (ISP) m/z=275.0 [(M+H)+].
Reaction SMILES: [OH-].[Na+].[C:3]1([CH2:9][SH:10])[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.[Cl:11][CH2:12][CH2:13][N:14]([CH2:38][CH2:39][Cl:40])[P:15]([N:31]([CH2:35][CH2:36][Cl:37])[CH2:32][CH2:33][Cl:34])(=[O:30])[O:16][CH2:17][CH2:18]OS(C1C=CC(Br)=CC=1)(=O)=O.C1(C)C=CC=CC=1>CO>[Cl:37][CH2:36][CH2:35][N:31]([P:15]([N:14]([CH2:13][CH2:12][Cl:11])[CH2:38][CH2:39][Cl:40])([O:16][CH2:17][CH2:18][S:10][CH2:9][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1)=[O:30])[CH2:32][CH2:33][Cl:34]
Reactant: O=P(OCCOS(=O)(=O)c1ccc(Br)cc1)(N(CCCl)CCCl)N(CCCl)CCCl
Reactant: SCc1ccccc1
Agent: [Na+]
Agent: [OH-]
Solvent: CO
Solvent: Cc1ccccc1
Product: O=P(OCCSCc1ccccc1)(N(CCCl)CCCl)N(CCCl)CCCl
Reaction time: 0.08 h

Procedure:
Sodium hydroxide, 6.4 g (161 mmol), was dissolved in 100 mL methanol under nitrogen at room temperature, and α-toluenethiol, 9.52 mL (10 g, 80.5 mmol), was added. After the resulting mixture was stirred for 5 minutes, 2-(4-bromobenzenesulfonyloxy)ethyl tetrakis(2-chloroethyl)phosphorodiamidate, 80.5 mL of 1 M solution in toluene (80.5 mmol), was added with stirring. A precipitate formed within 1 minute of the addition, and stirring was continued. Analysis of the reaction after 2 hours showed that the reaction was nearly complete, and stirring was continued overnight at room temperature. Analysis then showed that the reaction was complete, and stirring was stopped and the reaction mixture allowed to stand and then filtered to remove the precipitated sodium 4-bromobenzenesulfonate. The methanol was removed from the filtrate by evaporation and the residue was dissolved in 250 mL isopropyl acetate. The isopropyl acetate solution was washed with aqueous sodium hydroxide (100 mL of 1 M), water (100 mL), and brine (100 mL), and was then dried over anhydrous sodium sulfate and filtered. The isopropyl acetate was removed by vacuum evaporation to give an oil, which was dried under vacuum at 40° C. overnight, giving 40.4 g of α-[[2-[[bis[bis(2-chloroethyl)amino]phosphinyl]oxy]ethyl]thio]toluene as an orange oil containing residual toluene. HPLC analysis of the product showed a purity of 96.8%. 1H NMR: δ 7.16-7.33 (m, 5H), 4.04-4.06 (m, 2H), 3.74 (s, 2H), 3.60-3.65 (m, 8H), 3.36-3.43 (m, 8H), 2.69 (t, 2H).
Reaction SMILES: [C:1]([N:4]1[C:13]2[C:8](=[C:9]([NH:15][C:16](=[O:18])[CH3:17])[CH:10]=[CH:11][C:12]=2[CH3:14])[C:7](=[O:19])[C:6](=[N:20]O)[CH2:5]1)(=[O:3])[CH3:2].[C:22](NC1C=CC=C2C=1C(=O)C(=NO)CC2)(=[O:24])[CH3:23]>>[C:1]([N:4]1[C:13]2[C:8](=[C:9]([NH:15][C:16](=[O:18])[CH3:17])[CH:10]=[CH:11][C:12]=2[CH3:14])[C:7](=[O:19])[CH:6]([NH:20][C:22](=[O:24])[CH3:23])[CH2:5]1)(=[O:3])[CH3:2]
Reactant: CC(=O)Nc1ccc(C)c2c1C(=O)C(=NO)CN2C(C)=O
Reactant: CC(=O)Nc1cccc2c1C(=O)C(=NO)CC2
Product: CC(=O)Nc1ccc(C)c2c1C(=O)C(NC(C)=O)CN2C(C)=O

Procedure:
The procedure of Example 1-(3) was followed by using 2.89 gm of the compound prepared in (2) above instead of 8-acetylamino-2-hydroxyimino-1-tetralone. The reaction product was post-treated to obtain 1.65 gm of the title compound.
Reaction SMILES: [CH2:1]([C:5]1[CH:6]=[C:7]([OH:12])[C:8](=[CH:10][CH:11]=1)[OH:9])[CH2:2][CH2:3][CH3:4].C(N(CC)CC)C.[C:20](Cl)(=[O:24])[C:21](Cl)=[O:22]>CCOCC>[CH2:1]([C:5]1[CH:11]=[CH:10][C:8]2[O:9][C:20](=[O:24])[C:21](=[O:22])[O:12][C:7]=2[CH:6]=1)[CH2:2][CH2:3][CH3:4]
Reactant: CCCCc1ccc(O)c(O)c1
Reactant: O=C(Cl)C(=O)Cl
Solvent: CCN(CC)CC
Solvent: CCOCC
Product: CCCCc1ccc2oc(=O)c(=O)oc2c1
Temperature: 25 °C
Yield: 95.4 %

Procedure:
A mixture of 4.16 g (25 mM) of 4-n-butylcatechol, 5.06 g (50 mM) of triethylamine and 50 ml of dry ether was cooled in an ice water bath so to maintain the temperature at 5° C. or below. The mixture was added dropwise over 2 hours under stirring with a solution of 3.50 g (28 mM) of oxalyl chloride in 10 ml of dry ether. After completing the dropwise addition, the temperature of the reaction mixture was gradually raised to the room temperature and then aging was conducted for an hour. The resultant mixture was heated under reflux for 3 hours in order to complete the aging. The separated crystals of triethyl ammonium chloride was filtered. After thoroughly washing the crystals with ether, the ether solution was collected and dried with anhydrous sodium sulfate. After distilling off ether, the reaction product was recrystallized from a solvent mixture of carbontetrachloride and petroleum benzine to obtain 5.26 g (23 mM) of 6-n-butyl-1,4-benzodioxine-2,3-dione 2/5 hydrate as colorless crystals having a melting point of 88°-93° C.
Reaction SMILES: [OH:1][C:2]1[CH:12]=[CH:11][CH:10]=[CH:9][C:3]=1[C:4]([O:6][CH2:7][CH3:8])=[O:5].[C:13]([O:17][C:18]([NH:20][CH:21]([CH2:25][C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1)[C:22](O)=[O:23])=[O:19])([CH3:16])([CH3:15])[CH3:14].CCN=C=NCCCN(C)C.CN(C1C=CC=CN=1)C>C(Cl)Cl>[C:13]([O:17][C:18]([NH:20][CH:21]([CH2:25][C:26]1[CH:27]=[CH:28][CH:29]=[CH:30][CH:31]=1)[C:22]([O:1][C:2]1[CH:12]=[CH:11][CH:10]=[CH:9][C:3]=1[C:4]([O:6][CH2:7][CH3:8])=[O:5])=[O:23])=[O:19])([CH3:16])([CH3:14])[CH3:15]
Reactant: CC(C)(C)OC(=O)NC(Cc1ccccc1)C(=O)O
Reactant: CCOC(=O)c1ccccc1O
Agent: CCN=C=NCCCN(C)C
Agent: CN(C)c1ccccn1
Solvent: ClCCl
Product: CCOC(=O)c1ccccc1OC(=O)C(Cc1ccccc1)NC(=O)OC(C)(C)C
Temperature: 25 °C
Reaction time: 3 h
Yield: 96.7 %

Procedure:
To a solution of ethyl 2-hydroxybenzoate (0.5 g, 3.0 mmol) in CH2Cl2 (8 mL) was added 2-(tert-butoxycarbonylamino)-3-phenylpropanoic acid (0.8 g, 3.0 mmol), EDCI (0.63 g, 3.3 mmol) and dimethylaminopyridine (0.037 g, 0.3 mmol). The reaction was stirred (RT, 3 h) and then partitioned between CH2Cl2 and brine. The aqueous layer was extracted with CH2Cl2 and the combined organic extracts were dried over MgSO4. The crude material was purified by silica chromatography (0-10% MeOH/CH2Cl2) to afford 1.2 g of ethyl 2-(2-(tert-butoxycarbonylamino)-3-phenylpropanoyloxy)benzoate. Mass calculated for C235H27NO6=413.46. found: [M+Na]+=437.1.
Reaction SMILES: [H-].[Na+].[C:3]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])(=[O:12])[CH2:4][C:5]([O:7][C:8]([CH3:11])([CH3:10])[CH3:9])=[O:6].[Cl:18][C:19]1[CH:20]=[C:21]([CH:24]=[C:25]([O:27][C:28]2[C:33]([N+:34]([O-:36])=[O:35])=[CH:32][CH:31]=[C:30](F)[C:29]=2[F:38])[CH:26]=1)[C:22]#[N:23].C(O)(=O)CC(CC(O)=O)(C(O)=O)O>CCOC(C)=O.C1COCC1>[Cl:18][C:19]1[CH:26]=[C:25]([O:27][C:28]2[C:29]([F:38])=[C:30]([CH:4]([C:5]([O:7][C:8]([CH3:9])([CH3:10])[CH3:11])=[O:6])[C:3]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])[CH:31]=[CH:32][C:33]=2[N+:34]([O-:36])=[O:35])[CH:24]=[C:21]([C:22]#[N:23])[CH:20]=1
Reactant: CC(C)(C)OC(=O)CC(=O)OC(C)(C)C
Reactant: N#Cc1cc(Cl)cc(Oc2c([N+](=O)[O-])ccc(F)c2F)c1
Agent: O=C(O)CC(O)(CC(=O)O)C(=O)O
Agent: [H-]
Agent: [Na+]
Solvent: CCOC(C)=O
Solvent: C1CCOC1
Product: CC(C)(C)OC(=O)C(C(=O)OC(C)(C)C)c1ccc([N+](=O)[O-])c(Oc2cc(Cl)cc(C#N)c2)c1F
Temperature: 0 °C
Reaction time: 0.25 h

Procedure:
Sodium hydride (60% dispersion in oil, 2.16 g, 54.1 mmol) was added to anhydrous THF (50 mL) and cooled to 0° C. under nitrogen. Di-tert-butyl malonate (4.65 g, 24.8 mmol) was added dropwise and the reaction mixture was stirred 15 min and allowed to warm to RT. The reaction was cooled to 0° C. and 3-chloro-5-[(2,3-difluoro-6-nitrophenyl)oxy]benzonitrile (7.0 g, 22.5 mmol) was added dropwise in a minimal amount of THF. The reaction was allowed to warm to RT and stirred for 3 h then 10% aqueous citric acid (50 ml) and EtOAc (50 mL) were added. The layers were separated and the aqueous layer was extracted with EtOAc (2×50 mL). The organic extracts were combined, washed with brine, dried over Na2SO4, filtered and evaporated to afford the title compound as an oil. 1H NMR (400 MHz, DMSO-d6): 6 ppm 8.13 (dd, 1H), 7.84 (d, 1H), 7.65 (dd, 1H), 7.59-7.61 (m, 1H), 7.56-7.59 (m, 1H), 5.10 (s, 1H), 1.40 (s, 18H). MS: m/z 507.2 (M+1).
Reaction SMILES: [CH3:1][O:2][C:3](=[O:22])[C:4]1[CH:13]=[C:12]([O:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][Cl:21])[CH:11]=[C:6]([C:7]([O:9][CH3:10])=[O:8])[CH:5]=1.[H][H]>C(OCC)(=O)C.CCCCCC.C(OCC)(=O)C>[CH3:10][O:9][C:7]([CH:6]1[CH2:11][CH:12]([O:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][Cl:21])[CH2:13][CH:4]([C:3]([O:2][CH3:1])=[O:22])[CH2:5]1)=[O:8]
Reactant: [H][H]
Reactant: COC(=O)c1cc(OCCCCCCCl)cc(C(=O)OC)c1
Solvent: CCOC(C)=O
Solvent: CCCCCC
Product: COC(=O)C1CC(OCCCCCCCl)CC(C(=O)OC)C1
Temperature: 25 °C

Procedure:
7.5 g (22.8 mmol) 5-[(6-chlorohexyl)oxy]isophthalic acid dimethyl ester (example 6) were dissolved in 75 ml ethyl acetate and charged into a steel autoclave. After addition of 3 g of a hydrogenation catalyst (5% Rh/Alox, Johnson Matthey Company) the vessel was closed and the compound was hydrogenated at a reaction temperature of 70° C. using a constant hydrogen pressure of 18 bar until no further hydrogen uptage was observed (approx. 4 hours). The reaction suspension was cooled to room temperature, filtered and concentrated under vacuum to dryness. The crude product was essentially a cis/trans mixture of 5-[(6-chlorohexyl)oxy]-1,3-cyclohexanedicarboxylic acid dimethyl ester. The pure cis-compound was isolated as a colourless oil by chromatography on silica gel using hexane/ethyl acetate (4:1) as eluent. (yield: 6.1 g, 80%).
Reaction SMILES: [NH:1]1[C:9]2C(=CC=CC=2)[CH:3]=[CH:2]1.C([N:17]1[C:29]2[C:28]([OH:30])=[C:27]3[N:31](C(OC(C)(C)C)=O)[C:32]4[CH:33]=[CH:34][C:35]([Br:38])=[CH:36][C:37]=4[C:26]3=[CH:25][C:24]=2[C:23]2[C:18]1=[CH:19][CH:20]=[C:21]([Br:46])[CH:22]=2)(OC(C)(C)C)=O>>[Br:46][C:21]1[CH:22]=[C:23]2[C:18](=[CH:19][CH:20]=1)[NH:17][C:29]1[C:28]([O:30][CH2:3][CH2:2][NH:1][CH3:9])=[C:27]3[NH:31][C:32]4[CH:33]=[CH:34][C:35]([Br:38])=[CH:36][C:37]=4[C:26]3=[CH:25][C:24]2=1
Reactant: CC(C)(C)OC(=O)n1c2ccc(Br)cc2c2cc3c4cc(Br)ccc4n(C(=O)OC(C)(C)C)c3c(O)c21
Reactant: c1ccc2[nH]ccc2c1
Product: CNCCOc1c2[nH]c3ccc(Br)cc3c2cc2c1[nH]c1ccc(Br)cc12

Procedure:
The title compound was prepared in a manner analogous to Example 28 except the starting indole is 5,7-diBOC-2,10-dibromo-6-hydroxyindolo[2,3-b]carbazole. 1H-NMR (400 MHz, DMSO-d6) δ ppm 8.65 (s, 1H), 8.26 (d, J=1.2 Hz, 2H), 7.47-7.37 (m, 4H), 4.31 (t, J=5.2 Hz, 2H), 2.88 (t, J=5.2 Hz, 2H), 2.39 (s, 3H); MS (ESI) m/z 486.0 (M−H)−; MS (ESI) m/z 487.9 (M+H)+
Reaction SMILES: [CH2:1]([O:17][CH2:18][CH2:19][CH:20]([OH:23])[CH2:21][OH:22])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH3:16].[C:24](Cl)([C:37]1[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=1)([C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1)[C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1>N1C=CC=CC=1>[CH2:1]([O:17][CH2:18][CH2:19][CH:20]([OH:23])[CH2:21][O:22][C:24]([C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1)([C:37]1[CH:38]=[CH:39][CH:40]=[CH:41][CH:42]=1)[C:31]1[CH:32]=[CH:33][CH:34]=[CH:35][CH:36]=1)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH3:16]
Reactant: ClC(c1ccccc1)(c1ccccc1)c1ccccc1
Reactant: CCCCCCCCCCCCCCCCOCCC(O)CO
Solvent: c1ccncc1
Product: CCCCCCCCCCCCCCCCOCCC(O)COC(c1ccccc1)(c1ccccc1)c1ccccc1
Temperature: 0 °C
Reaction time: 24 h
Yield: 109 %

Procedure:
To a solution of 30 g of 4-(hexadecyloxy)-1,2-butanediol in 135 ml of dry pyridine was added 37.95 g of trityl chloride. The solution was allowed to stand under argon for 24 hours and was then poured into 700 ml of ice water and extracted three times with ether. The ether extracts were combined, washed with ice cold 5% hydrochloric acid, then saturated salt solution, dried and evaporated to dryness. The residue was mixed with petroleum ether, allowed to stand 72 hours, the solid removed and the mother liquor taken to dryness, giving 56.65 g of the desired compound as an oil.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:27]=[CH:26][CH:25]=[CH:24][C:4]=1[CH2:5][O:6][CH2:7][CH2:8][CH2:9][O:10][C:11]1[CH:16]=[CH:15][C:14]([CH:17]2[CH2:22][CH2:21][NH:20][CH2:19][CH:18]2[OH:23])=[CH:13][CH:12]=1.C(=O)([O-])[O-].[Na+].[Na+].[CH:34]([O:36][CH2:37][C:38]1[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=1)=[O:35]>C(OCC)(=O)C>[OH:23][CH:18]1[CH:17]([C:14]2[CH:15]=[CH:16][C:11]([O:10][CH2:9][CH2:8][CH2:7][O:6][CH2:5][C:4]3[CH:24]=[CH:25][CH:26]=[CH:27][C:3]=3[O:2][CH3:1])=[CH:12][CH:13]=2)[CH2:22][CH2:21][N:20]([C:34]([O:36][CH2:37][C:38]2[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=2)=[O:35])[CH2:19]1
Reactant: COc1ccccc1COCCCOc1ccc(C2CCNCC2O)cc1
Reactant: O=COCc1ccccc1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: CCOC(C)=O
Product: COc1ccccc1COCCCOc1ccc(C2CCN(C(=O)OCc3ccccc3)CC2O)cc1
Reaction time: 0.17 h

Procedure:
The solution of 3.0 g of 4-{4-[3-(2-methoxybenyloxy)propoxy]phenyl}piperidin-3-ol in 30 ml of ethyl acetate is cooled to 0° C. with stirring and admixed with 30 ml of saturated aqueous sodium carbonate solution. At 0-5° C., 1.32 ml of benzyl formate are added dropwise. After 10 minutes, the reaction mixture is poured onto water (250 ml) and extracted with ethyl acetate (2×250 ml). The organic phases are washed with brine (1×250 ml), dried over sodium sulphate and concentrated by evaporation. The title compound is obtained as a yellow oil from the residue by means of flash chromatography (SiO2 60F). Rf=0.35 (1:1 EtOAc-heptane); Rt=5.94. m.p. 71-73° C.
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8](=O)[C@@H:9]([NH:11][C:12](=[O:18])[O:13][C:14]([CH3:17])([CH3:16])[CH3:15])[CH3:10])=[CH:4][CH:3]=1.[CH3:20][C:21]([S@:24]([NH2:26])=[O:25])([CH3:23])[CH3:22]>>[C:21]([S@:24]([N:26]=[C:8]([C:5]1[CH:6]=[CH:7][C:2]([F:1])=[CH:3][CH:4]=1)[C@@H:9]([NH:11][C:12](=[O:18])[O:13][C:14]([CH3:17])([CH3:16])[CH3:15])[CH3:10])=[O:25])([CH3:23])([CH3:22])[CH3:20]
Reactant: CC(C)(C)[S@](N)=O
Reactant: C[C@H](NC(=O)OC(C)(C)C)C(=O)c1ccc(F)cc1
Product: C[C@H](NC(=O)OC(C)(C)C)C(=N[S@](=O)C(C)(C)C)c1ccc(F)cc1

Procedure:
Condensation of t-butyl N-[(1S)-2-(4-fluorophenyl)-1-methyl-2-oxoethyl]carbamate with (R)-(+)-2-methyl-2-propanesulfinamide in the presence of a dehydrating agent gave t-butyl N-[(1S)-2-[((R)-t-butylsulfinyl)imino]-2-(4-fluorophenyl)-1-methylethyl]carbamate. To a solution of the sulfinylimine compound (80 mg) in toluene (2 mL) was added 1.0M trimethylaluminum/hexane solution (0.43 mL) at −78° C., followed by stirring for 5 minutes. The resulting solution was gradually added dropwise at −78° C. to a solution of 2-fluoro-4-pyridyllithium, which had been prepared by reacting 4-fluoro-2-bromopyridine (114 mg) with 1.56M butyllithium/hexane solution (0.46 mL) in diethyl ether (3 mL) at −78° C. After completion of the dropping, tetrahydrofuran (3 mL) was added to the reaction mixture, followed by stirring at −78° C. for 2.5 hours. Saturated brine was added to the reaction mixture and the temperature was elevated to room temperature. The reaction solution was filtered through a Celite pad, and the organic layer in the filtrate was dried over anhydrous magnesium sulfate. After removal of the magnesium sulfate by filtration, the organic solvent was evaporated off in vacuo. The residue was purified by column chromatography on silica gel (C-300; hexane:ethyl acetate=2:1) to give t-butyl N-[(1S,2S)-2-[(t-butylsulfinyl)amino]-2-(4-fluorophenyl)-2-(2-fluoro-4-pyridyl)-1-methylethyl]carbamate (49 mg). The product was treated with 4N hydrogen chloride/dioxane solution to give the optically active diamine indicated in the title.
Reaction SMILES: [C:1]([NH:4][C:5]1[CH:14]=[C:13]([C:15]2[CH:20]=[CH:19][C:18]([N+:21]([O-:23])=[O:22])=[CH:17][CH:16]=2)[C:12]2[C:7](=[CH:8][CH:9]=[C:10]([Cl:24])[CH:11]=2)[N:6]=1)(=O)[CH3:2].C(O)C.Cl>C1COCC1>[Cl:24][C:10]1[CH:11]=[C:12]2[C:7](=[CH:8][CH:9]=1)[N:6]=[C:5]([NH:4][CH2:1][CH3:2])[CH:14]=[C:13]2[C:15]1[CH:20]=[CH:19][C:18]([N+:21]([O-:23])=[O:22])=[CH:17][CH:16]=1
Reactant: CC(=O)Nc1cc(-c2ccc([N+](=O)[O-])cc2)c2cc(Cl)ccc2n1
Agent: Cl
Solvent: C1CCOC1
Solvent: CCO
Product: CCNc1cc(-c2ccc([N+](=O)[O-])cc2)c2cc(Cl)ccc2n1
Temperature: 25 °C
Reaction time: 12 h

Procedure:
500 mg of 2-acetylamino-6-chloro-4-(4-nitrophenyl)quinoline (compound 1c) were suspended in 10 ml of THF and, under argon, added in portions to 2.9 ml of borane-THF complex. Foaming was followed by formation of a yellow solution. After stirring at room temperature for 12 hours, the solution was mixed with 5 ml of ethanol and 2 ml of concentrated HCl and heated on a water bath, cooled and distilled to remove water. The residue was mixed with water, made alkaline with 2N NaOH, extracted with ethyl acetate and washed with water. The product was purified by MPLC chromatography using an MPRC cartridge with a mixture of 1 part by volume of ethyl acetate, 2 parts by volume of toluene. A yellow solid product was isolated.