Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [O:1]1[C:5]2[CH:6]=[CH:7][C:8]([S:10]([N:13]([CH2:18][C@@H:19]([OH:43])[C@@H:20]([N:28](CC3C=CC=CC=3)CC3C=CC=CC=3)[CH2:21][C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=3)[CH2:14][CH:15]([CH3:17])[CH3:16])(=[O:12])=[O:11])=[CH:9][C:4]=2[O:3][CH2:2]1.[CH3:44][S:45]([OH:48])(=[O:47])=[O:46].O>CO.[OH-].[OH-].[Pd+2]>[O:1]1[C:5]2[CH:6]=[CH:7][C:8]([S:10]([N:13]([CH2:18][C@@H:19]([OH:43])[C@@H:20]([NH2:28])[CH2:21][C:22]3[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=3)[CH2:14][CH:15]([CH3:17])[CH3:16])(=[O:11])=[O:12])=[CH:9][C:4]=2[O:3][CH2:2]1.[CH3:44][S:45]([OH:48])(=[O:47])=[O:46]
Reactant: CC(C)CN(C[C@@H](O)[C@H](Cc1ccccc1)N(Cc1ccccc1)Cc1ccccc1)S(=O)(=O)c1ccc2c(c1)OCO2
Agent: [Pd+2]
Agent: CS(=O)(=O)O
Agent: [OH-]
Solvent: CO
Solvent: O
Product: CC(C)CN(C[C@@H](O)[C@@H](N)Cc1ccccc1)S(=O)(=O)c1ccc2c(c1)OCO2
Reaction time: 18 h
Yield: 87.1 %

Procedure:
Crude 1-[N-[(1,3-benzodioxol-5-yl)sulfonyl]-N-(2-methylpropyl)amino]-3(S)-[bis(phenylmethyl)amino]-4-phenyl-2(R)-butanol (6.2 g, 0.010 moles) was dissolved in methanol (40 mL). Methanesulfonic acid (0.969 g, 0.010 moles) and water (5 mL) were then added to the solution. The mixture was placed in a 500 mL Parr hydrogenation bottle containing 20% Pd(OH)2 on carbon (255 mg, 50% water content). The bottle was placed in the hydrogenator and purged 5 times with nitrogen and 5 times with hydrogen. The reaction was allowed to proceed at 35° C. with 63 PSI hydrogen pressure for 18 hours. Additional catalyst (125 mg) was added and, after purging, the hydrogenation continued for and additional 20 hours. The mixture was filtered through celite which was washed with methanol (2×10 mL). Approximately one third of the methanol was removed under reduced pressure. The remaining methanol was removed by aziotropic distillation with toluene at 80 torr. Toluene was added in 15, 10, 10 and 10 mL portions. The product crystallized from the mixture and was filtered and washed twice with 10 mL portions of toluene. The solid was dried at room temperature at 1 torr for 6 hours to yield the amine salt (4.5 g, 84%). HPLC/MS (electrospray) was consistent with the desired product (m/z 421 [M+H]+).
Reaction SMILES: [NH2:1][CH2:2][CH2:3][C:4]1[CH:9]=[CH:8][C:7]([OH:10])=[CH:6][CH:5]=1.[CH:11](=O)[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1.[BH4-].[Na+]>CO>[CH2:11]([NH:1][CH2:2][CH2:3][C:4]1[CH:9]=[CH:8][C:7]([OH:10])=[CH:6][CH:5]=1)[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1
Reactant: NCCc1ccc(O)cc1
Reactant: O=Cc1ccccc1
Agent: [BH4-]
Agent: [Na+]
Solvent: CO
Product: Oc1ccc(CCNCc2ccccc2)cc1
Temperature: 0 °C
Reaction time: 8 h
Yield: 91 %

Procedure:
Combine tyramine (5.0 g, 36.4 mmol), benzaldehyde (3.8 ml, 37.2 mmol) in MeOH (46 mL), heat at reflux for 2 h. Cool the mixture at 0° C. and add NaBH4 (1.44 g, 38.2 mmol). Stir at room temperature overnight. Remove most of MeOH, add H2O and stir for 2 h. Filter the mixture and wash the white solid with water. Dry the solid precipitate under vacuum at 40° C. overnight to afford the title compound (7.53 g, 91%). Electrospray MS M+1 ion=228. 1H-NMR (methanol-d4, 300 MHz): 7.40-7.20 (m, 5H), 7.03-6.95 (m, 2H), 6.73-6.65 (m, 2H), 3.75 (s, 2H), 2.85-2.65 (m, 4H).
Reaction SMILES: [F:1][C:2]1[CH:8]=[CH:7][CH:6]=[C:5]([F:9])[C:3]=1[NH2:4].C(N(CC)CC)C.[CH:17]1([O:22][C:23]2[CH:24]=[C:25]([CH:29]=[CH:30][C:31]=2[O:32][CH3:33])[C:26](Cl)=[O:27])[CH2:21][CH2:20][CH2:19][CH2:18]1>ClCCl>[F:1][C:2]1[CH:8]=[CH:7][CH:6]=[C:5]([F:9])[C:3]=1[NH:4][C:26](=[O:27])[C:25]1[CH:29]=[CH:30][C:31]([O:32][CH3:33])=[C:23]([O:22][CH:17]2[CH2:18][CH2:19][CH2:20][CH2:21]2)[CH:24]=1
Reactant: COc1ccc(C(=O)Cl)cc1OC1CCCC1
Reactant: Nc1c(F)cccc1F
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: COc1ccc(C(=O)Nc2c(F)cccc2F)cc1OC1CCCC1
Yield: 46.5 %

Procedure:
A stirred solution of 2,6-difluoroaniline (1.52 g) and triethylamine (1.19 g) in dichloromethane (50 mL) at room temperature is treated dropwise with a solution of 3-cyclopentyloxy-4-methoxybenzoyl chloride (3.0 g), that is prepared as described hereinafter in Reference Example 3) in dichloro-methane (50 mL). The solution is stirred and heated at reflux for 4 hours, then it is cooled, washed with water and dried over magnesium sulfate. The solution is concentrated and the resulting residue is recrystallized from ethyl acetate, to give N-(2,6-difluorophenyl)-3-cyclopentyloxy-4-methoxybenzamide (1.9 g), m.p. 158-160° C. [NMR(CDCl3): 1.55-1.7(m,3H),1.8-2.05(m,5H), 3.93(s,3H),4.85(m,1H),6.9(d,1H), 6.95-7.03(m,2H),7.2-7.3(m,1H),7.35(bs,1H), 7.45(q,1H),7.53(d,1H); Elemental analysis: C,65.1; H,5.6; F,10.4; N,4.2%; Calculated: C,65.7; H,5.5; F,10.9; N,40%].
Reaction SMILES: [F:1][C:2]1([F:44])[CH2:7][C@H:6]([O:8][C:9]2[C:14]([CH3:15])=[CH:13][C:12]([S:16]([N:19](CC3C=CC(OC)=CC=3OC)[C:20]3[CH:25]=[CH:24][N:23]=[CH:22][N:21]=3)(=[O:18])=[O:17])=[C:11]([F:37])[CH:10]=2)[C@@H:5]([C:38]2[N:42]([CH3:43])[N:41]=[CH:40][CH:39]=2)[CH2:4][CH2:3]1.C([SiH](CC)CC)C.FC(F)(F)C(O)=O>ClCCl>[F:44][C:2]1([F:1])[CH2:7][C@H:6]([O:8][C:9]2[C:14]([CH3:15])=[CH:13][C:12]([S:16]([NH:19][C:20]3[CH:25]=[CH:24][N:23]=[CH:22][N:21]=3)(=[O:18])=[O:17])=[C:11]([F:37])[CH:10]=2)[C@@H:5]([C:38]2[N:42]([CH3:43])[N:41]=[CH:40][CH:39]=2)[CH2:4][CH2:3]1
Reactant: COc1ccc(CN(c2ccncn2)S(=O)(=O)c2cc(C)c(O[C@H]3CC(F)(F)CC[C@@H]3c3ccnn3C)cc2F)c(OC)c1
Agent: CC[SiH](CC)CC
Solvent: O=C(O)C(F)(F)F
Solvent: ClCCl
Product: Cc1cc(S(=O)(=O)Nc2ccncn2)c(F)cc1O[C@H]1CC(F)(F)CC[C@@H]1c1ccnn1C
Yield: 53.1 %

Procedure:
The reaction and aftertreatment were conducted in the same manner as in Example 1b by using the 4-{[(1S,2R)-5,5-difluoro-2-(1-methyl-1H-pyrazol-5-yl)cyclohexyl]oxy}-N-(2,4-dimethoxybenzyl)-2-fluoro-5-methyl-N-(pyrimidin-4-yl)benzenesulfonamide (198 mg, 0.313 mmol) prepared in Example 137a, triethylsilane (0.10 mL), trifluoroacetic acid (1.0 mL) and dichloromethane (1.0 mL), to yield the title compound (80 mg, 53%) as a colorless solid.
Reaction SMILES: [CH3:1][C:2]1[CH:7]=[CH:6][C:5]([S:8]([NH:11][CH2:12][CH2:13][C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=2[O:20][CH2:21][CH2:22][N:23]2[CH2:28][CH2:27][CH2:26][CH2:25][CH2:24]2)(=[O:10])=[O:9])=[CH:4][CH:3]=1.[C:29]([OH:33])(=[O:32])[CH:30]=O>>[N:23]1([CH2:22][CH2:21][O:20][C:15]2[CH:16]=[CH:17][CH:18]=[C:19]3[C:14]=2[CH2:13][CH2:12][N:11]([S:8]([C:5]2[CH:4]=[CH:3][C:2]([CH3:1])=[CH:7][CH:6]=2)(=[O:10])=[O:9])[CH:30]3[C:29]([OH:33])=[O:32])[CH2:28][CH2:27][CH2:26][CH2:25][CH2:24]1
Reactant: O=CC(=O)O
Reactant: Cc1ccc(S(=O)(=O)NCCc2ccccc2OCCN2CCCCC2)cc1
Product: Cc1ccc(S(=O)(=O)N2CCc3c(OCCN4CCCCC4)cccc3C2C(=O)O)cc1

Procedure:
4-Methyl-N-{2-[2-(2-piperidin-1-ylethoxy)phenyl]ethyl}benzenesulfonamide is reacted with glyoxylic acid in analogy to the method described for Example 20.
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:13]=[C:12]([CH3:14])[C:11]([C:15]([OH:17])=O)=[CH:10][N:9]=2)=[CH:4][CH:3]=1.C(N(C(C)C)CC)(C)C.[CH3:27][NH:28][S:29]([C:32]1[CH:33]=[C:34]([CH:37]=[CH:38][CH:39]=1)[CH2:35][NH2:36])(=[O:31])=[O:30]>CN(C=O)C>[CH3:27][NH:28][S:29]([C:32]1[CH:33]=[C:34]([CH:37]=[CH:38][CH:39]=1)[CH2:35][NH:36][C:15]([C:11]1[C:12]([CH3:14])=[N:13][C:8]([C:5]2[CH:4]=[CH:3][C:2]([F:1])=[CH:7][CH:6]=2)=[N:9][CH:10]=1)=[O:17])(=[O:30])=[O:31]
Reactant: CNS(=O)(=O)c1cccc(CN)c1
Reactant: Cc1nc(-c2ccc(F)cc2)ncc1C(=O)O
Solvent: CN(C)C=O
Solvent: CCN(C(C)C)C(C)C
Product: CNS(=O)(=O)c1cccc(CNC(=O)c2cnc(-c3ccc(F)cc3)nc2C)c1
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 50.7 %

Procedure:
A mixture of 2-(4-fluorophenyl)-4-methylpyrimidine-5-carboxylic acid (232 mg, 1 mmol) and O-(7-azabenzotriazol-1-yl)-N,N,N,N-tetramethyluronium hexafluorophosphate (380 mg 1 mmol) in dry DMF (12 mL) is treated with diisopropylethylamine (0.18 mL) and stirred at room temperature for 30 min. A solution of 3-methylsulfamoylbenzylamine (300 mg, 1.5 mmol) in dry DMF (1.5 mL) is added and the mixture is stirred at room temperature for 24 hours. The solvent is removed and the residue is partitioned between EtOAc and water. The organic phase is separated, washed with saturated NaHCO3, water and brine, dried (MgSO4), filtered and concentrated in vacuo. The residue is purified by column chromatography eluting with 60% EtOAc in heptane to afford 2-(4-fluorophenyl)-4-methylpyrimidine-5-carboxylic acid 3-methylsulfamoyl-benzylamide (210 mg, 52%) as a solid. MS: 415 (M+H); 1H NMR (300 MHz, DMSO-d6): δ 2.42 (s, 3H), 2.63 (s, 3H), 4.60 (d, 2H), 7.37-7.40 (t, 2H), 7.50 (s, 1H), 7.60-7.75 (m, 3H), 7.80 (s, 1H), 8.45-8.50 (dd, 2H), 8.88 (s, 1H), 9.30 (t, 1H).
Reaction SMILES: [C:1]([O:5][C:6]([N:8]1[CH2:11][CH:10]([NH:12][C:13]2[CH:14]=[C:15]3[C:24](=[CH:25][C:26]=2Br)[O:23][CH2:22][C:21]2[N:16]3[CH:17]([CH3:29])[C:18](=[O:28])[NH:19][N:20]=2)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[C:30]1(B(O)O)[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1.C([O-])([O-])=O.[K+].[K+]>O1CCOCC1.O>[C:1]([O:5][C:6]([N:8]1[CH2:11][CH:10]([NH:12][C:13]2[CH:14]=[C:15]3[C:24](=[CH:25][C:26]=2[C:30]2[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=2)[O:23][CH2:22][C:21]2[N:16]3[CH:17]([CH3:29])[C:18](=[O:28])[NH:19][N:20]=2)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]
Reactant: OB(O)c1ccccc1
Reactant: CC1C(=O)NN=C2COc3cc(Br)c(NC4CN(C(=O)OC(C)(C)C)C4)cc3N21
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: C1COCCO1
Product: CC1C(=O)NN=C2COc3cc(-c4ccccc4)c(NC4CN(C(=O)OC(C)(C)C)C4)cc3N21
Temperature: 110 °C
Yield: 71.4 %

Procedure:
A mixture of 3-(7-bromo-4-methyl-3-oxo-2,3,4,10-tetrahydro-9-oxa-1,2,4a-triaza-phenanthren-6-ylamino)-azetidine-1-carboxylic acid tert-butyl ester (1 g, 2.1 mmol), phenylboronic acid (0.79 g, 6.4 mmol), 1,1′-bis(diphenylphosphino)ferrocene-palladium(II)dichloride dichloromethane complex (0.351 g, 0.43 mmol) and K2CO3 (0.890 g, 6.4 mmol) in dioxane (24 mL) and water (4 mL) was heated at 110° C. overnight. The reaction mixture was cooled to ambient temperature and the solvent was removed in vacuo to give the crude product, which was purified by column chromatography (eluting with 10-40% EtOAc in petroleum ether) to give 3-(4-methyl-3-oxo-7-phenyl-2,3,4,10-tetrahydro-9-oxa-1,2,4a-triaza-phenanthren-6-ylamino)-azetidine-1-carboxylic acid tert-butyl ester (0.710 g racemate, 1.5 mmol, 71%) as an off-white powder. The racemic material was further separated by chiral SFC (Table 2, Method 1) to give two isomers: 3-(4(R)-methyl-3-oxo-7-phenyl-2,3,4,10-tetrahydro-9-oxa-1,2,4a-triaza-phenanthren-6-ylamino)-azetidine-1-carboxylic acid tert-butyl ester (Enantiomer 1, SFC (Table 1, Method 1), Rt=3.374 min., 0.281 g, 0.61 mmol, 29%) and 3-(4(S)-methyl-3-oxo-7-phenyl-2,3,4,10-tetrahydro-9-oxa-1,2,4a-triaza-phenanthren-6-ylamino)-azetidine-1-carboxylic acid tert-butyl ester (Enantiomer 2, SFC (Table 1, Method 1), Rt=4.333 min., 0.252 g, 26%). LC/MS (Table 1, Method 2) Rt=1.25 min.; MS m/z: 464 [M+H]+.
Reaction SMILES: Br[CH2:2][C:3]1[C:12](=[O:13])[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[O:5][C:4]=1[C:14]1[CH:19]=[CH:18][C:17]([OH:20])=[CH:16][CH:15]=1.[C-:21]#[N:22].[Na+].C(=O)([O-])[O-].[K+].[K+]>CN(C=O)C.O.CO>[OH:20][C:17]1[CH:18]=[CH:19][C:14]([C:4]2[O:5][C:6]3[C:11]([C:12](=[O:13])[C:3]=2[CH2:2][C:21]#[N:22])=[CH:10][CH:9]=[CH:8][CH:7]=3)=[CH:15][CH:16]=1
Reactant: O=c1c(CBr)c(-c2ccc(O)cc2)oc2ccccc12
Reactant: [C-]#N
Agent: O=C([O-])[O-]
Agent: [K+]
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: CO
Solvent: O
Product: N#CCc1c(-c2ccc(O)cc2)oc2ccccc2c1=O
Temperature: 25 °C
Reaction time: 0.5 h

Procedure:
A solution of 3-bromomethyl-2-(4-hydroxyphenyl)-4H-chromen-4-one (0.3 g, 0.8 mmol) in DMF (15 mL), water (15 mL), and NaCN (0.12 g, 2.4 mmol) was stirred at 45° C. for 24 h. The reaction mixture was extracted with EtOAc (3×100 mL) and concentrated to afford a solid residue. This residue was re-dissolved in MeOH (50 mL) and water (50 mL) and was mixed with potassium carbonate (1 g) and stirred at rt for 0.5 h. MeOH was removed, the aqueous layer was acidified with HCl (1 N) to pH=5. The solid was filtered off and then purified by column chromatography (hexane:EtOAc 1:2). The resulting solid was re-crystallized from dichloromethane and hexanes to give 2-(2-(4-hydroxyphenyl)-4-oxo-4H-chromen-3-yl)acetonitrile as a light yellow solid product (0.14 g, 63%). MS (ES) m/z: 278.94 (M+1), 277.93 (M); Mp. 258.2-259.5° C.
Reaction SMILES: [CH3:1][C:2]1[CH:3]=[CH:4][C:5]([N:11]2[N:15]=[CH:14]C=N2)=[C:6]([CH:10]=1)[C:7]([OH:9])=[O:8].[NH:16]1[CH:20]=NC=N1>>[CH3:1][C:2]1[CH:3]=[CH:4][C:5]([N:11]2[CH:20]=[N:16][CH:14]=[N:15]2)=[C:6]([CH:10]=1)[C:7]([OH:9])=[O:8]
Reactant: c1nc[nH]n1
Reactant: Cc1ccc(-n2nccn2)c(C(=O)O)c1
Product: Cc1ccc(-n2cncn2)c(C(=O)O)c1

Procedure:
The title compound was synthesized following the same general protocol as described for 5-methyl-2-(2H-1,2,3-triazol-2-yl)benzoic acid in Example A11 using 1H-1,2,4-triazole. ESI-MS (m/z): 204 [M+1]+.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:9](=[CH:10][CH:11]=1)[C:8](=[O:12])[CH2:7][CH2:6]2.[H-].[Na+].Br[CH2:16][CH2:17][CH2:18][CH:19]=[CH2:20]>CN(C=O)C.C(Cl)Cl>[CH2:16]([C:7]1([CH2:5][CH2:4][CH2:3][CH:11]=[CH2:10])[CH2:6][C:5]2[C:9](=[CH:10][CH:11]=[C:3]([O:2][CH3:1])[CH:4]=2)[C:8]1=[O:12])[CH2:17][CH2:18][CH:19]=[CH2:20]
Reactant: C=CCCCBr
Reactant: COc1ccc2c(c1)CCC2=O
Agent: [H-]
Agent: [Na+]
Solvent: ClCCl
Solvent: CN(C)C=O
Product: C=CCCCC1(CCCC=C)Cc2cc(OC)ccc2C1=O
Reaction time: 6 h

Procedure:
To a solution of 5-methoxy-1-indanone (2.5 g, 15.4 mmol) in DMF (20 mL) at rt was added NaH (1.8 g, 61% in oil, 46.2 mmol) and 5-bromo-1-pentene (5.48 mL, 46.2 mmol). After 6 h at rt, the solution was diluted with CH2Cl2 and quenched with saturated aqueous NH4Cl. The slurry was dried with MgSO4 and filtered through a plug of silica and rinsed with 10% EtOAc in hexanes. The filtrate was concentrated and provided crude 2,2-di(4-pentenyl)-5-methoxy-1-indanone.
Reaction SMILES: [CH3:1][O:2][C:3]([C:5]1[CH:10]=[CH:9][C:8]([S:11]([N:14]=[C:15]=[O:16])(=[O:13])=[O:12])=[CH:7][CH:6]=1)=[O:4].[NH2:17][C:18]1[CH:26]=[C:25]([Cl:27])[CH:24]=[CH:23][C:19]=1[C:20]([OH:22])=O>>[Cl:27][C:25]1[CH:26]=[C:18]2[C:19]([C:20](=[O:22])[N:14]([S:11]([C:8]3[CH:7]=[CH:6][C:5]([C:3]([O:2][CH3:1])=[O:4])=[CH:10][CH:9]=3)(=[O:13])=[O:12])[C:15](=[O:16])[NH:17]2)=[CH:23][CH:24]=1
Reactant: COC(=O)c1ccc(S(=O)(=O)N=C=O)cc1
Reactant: Nc1cc(Cl)ccc1C(=O)O
Product: COC(=O)c1ccc(S(=O)(=O)n2c(=O)[nH]c3cc(Cl)ccc3c2=O)cc1
Yield: 58.8 %

Procedure:
1.12 g (4.65 mmol) of 4-methoxycarbonylbenzenesulfonylisocyanate and 798 mg (4.65 mmol) of 2-amino-4-chlorobenzoic acid were treated in the same way as in Example 1 to obtain 1.08 g of the above-identified compound (yield 58.9%). Properties: colorless crystal, Melting point: >230° C., PMR (δppm, DMSO-d6): 3.91 (3H,s), 7.13 (1H,s), 7.23 (1H,d), 7.86 (1H,d), 8.20 (2H,d), 8.29 (2H,d), 11.80 (1H,br).
Reaction SMILES: [CH3:1][N:2]([CH3:5])[CH:3]=O.S(Cl)(Cl)=O.ClCCCl.[NH:14]1[C:23](=[O:24])[C:22]2[NH:21][CH:20]=[N:19][C:18]=2[N:17]=[C:15]1[NH2:16]>O>[CH3:1][N:2]([CH:5]=[N:16][C:15]1[NH:14][C:23](=[O:24])[C:22]2[NH:21][CH:20]=[N:19][C:18]=2[N:17]=1)[CH3:3]
Reactant: Nc1nc2nc[nH]c2c(=O)[nH]1
Reactant: CN(C)C=O
Solvent: O=S(Cl)Cl
Solvent: ClCCCl
Solvent: O
Product: CN(C)C=Nc1nc2nc[nH]c2c(=O)[nH]1
Temperature: 80 °C
Reaction time: 6 h
Yield: 85 %

Procedure:
131.6 g (1.8 mol) of N,N-dimethylformamide and 42.8 g (0.36 mol) of thionyl chloride were added to 500 ml of 1,2-dichloroethane, and then 45.3 g (0.3 mol) of guanine (manufactured by Sumika Fine Chemicals Co., Ltd.) was added, followed by stirring at 80° C. for 6 hours. After cooling, the reaction mixture was added to 1000 ml of water to separate out the water layer, and then the water layer was neutralized with sodium hydrogen carbonate. The precipitating crystal was collected by filtration and washed with 100 ml of water to yield 52.6 g (0.255 mol) of a white crystal of N-dimethylaminomethyleneguanine (yield 85%).
Reaction SMILES: CC#N.[OH2:4].[CH2:5]=[CH:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH3:16].C(Cl)Cl>CC#N>[CH2:7]([CH:6]1[CH2:5][O:4]1)[CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH3:16]
Reactant: O
Reactant: C=CCCCCCCCCCC
Solvent: ClCCl
Solvent: CC#N
Product: CCCCCCCCCCC1CO1
Yield: 99 %

Procedure:
Under a flow of F2 (10% in N2) of 20.0 ml min−1 (3.33 mmol h−1) passed through conduit 12, MeCN:H2O (4:1, 4.95 ml) was added to conduit 16 at a rate of 9.90 ml h−1 (110.0 mmol h−1) and dodec-1-ene 24 (0.18 g, 1.07 mmol) (in a 1:1 mixture of DCM:MeCN) was added to conduit 38 at a rate of 9.90 ml h−1. All reaction fluids were collected in pot 22 containing sodium bicarbonate solution 25 (50 ml). The reaction mixture was then added to another 25 ml of sodium bicarbonate solution, washed with DCM (3×75 ml), dried over MgSO4 and filtered. The solvent was removed under reduced pressure to yield 2-decyloxirane (0.195 g, 1.06 mmol, 99%) as a yellow oil, with no further purification required.
Reaction SMILES: C([SiH](CC)CC)C.[C:8]([C:12]1[C:17]2[CH:18]=[C:19]([CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH3:28])[O:20][C:16]=2[CH:15]=[CH:14][C:13]=1[OH:29])([CH3:11])([CH3:10])[CH3:9].FC(F)(F)C(O)=O>>[C:8]([C:12]1[C:17]2[CH2:18][CH:19]([CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH3:28])[O:20][C:16]=2[CH:15]=[CH:14][C:13]=1[OH:29])([CH3:11])([CH3:10])[CH3:9]
Reactant: CCCCCCCCc1cc2c(C(C)(C)C)c(O)ccc2o1
Agent: CC[SiH](CC)CC
Solvent: O=C(O)C(F)(F)F
Product: CCCCCCCCC1Cc2c(ccc(O)c2C(C)(C)C)O1
Temperature: 0 °C
Reaction time: 0.25 h
Yield: 82.8 %

Procedure:
Triethylsilane (2.8 ml) was added to 4-tert-butyl-5-hydroxy-2-octylbenzofuran (300 mg, 1.0 mmol) and, then, trifluoroacetic acid (1.4 ml) was added dropwise under ice cooling. The mixture was stirred first at 0° C. for 15 min, then at room temperature for 1 h., Thereafter, the mixture was poured into ice water and subjected to extraction with ethyl acetate. The organic layer was washed with a saturated aqueous solution of sodium hydrogen carbonate, dried over anhydrous magnesium sulfate and concentrated. The concentrate was purified by silica gel chromatography (chloroform) to afford 4-tert-butyl-5-hydroxy-2-octyl-2,3-dihydrobenzofuran [252 mg (yield, 83%)] as a colorless oil.
Reaction SMILES: [H-].[Na+].[Cl:3][C:4]1[CH:5]=[C:6]([Cl:34])[C:7]2[C:8]3[CH2:26][CH2:25][N:24](C(OC(C)(C)C)=O)[CH2:23][CH2:22][C:9]=3[N:10]([CH2:13][CH2:14][O:15][C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=3)[C:11]=2[CH:12]=1.[Cl:35]C1C=C(Cl)C2C3CCN(C(OC(C)(C)C)=O)CCC=3NC=2C=1.BrCCOC1C=CC=CC=1>CN(C=O)C>[ClH:3].[Cl:35][C:12]1[C:11]2[N:10]([CH2:13][CH2:14][O:15][C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=3)[C:9]3[CH2:22][CH2:23][NH:24][CH2:25][CH2:26][C:8]=3[C:7]=2[C:6]([Cl:34])=[CH:5][CH:4]=1
Reactant: CC(C)(C)OC(=O)N1CCc2[nH]c3cc(Cl)cc(Cl)c3c2CC1
Reactant: CC(C)(C)OC(=O)N1CCc2c(n(CCOc3ccccc3)c3cc(Cl)cc(Cl)c23)CC1
Agent: BrCCOc1ccccc1
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: Cl
Product: Clc1ccc(Cl)c2c1c1c(n2CCOc2ccccc2)CCNCC1
Reaction time: 0.42 h
Yield: 104.1 %

Procedure:
Preparation of tert-Butyl 8,10-dichloro-6-(2-phenoxyethyl)-1,4,5,6-tetrahydroazepino[4,5-b]indole-3(2H)-carboxylate Sodium hydride (60% dispersion in mineral oil, 51 mg, 1.3 mmol) was added to a solution of tert-butyl 8,10-dichloro-1,4,5,6-tetrahydroazepino[4,5-b]indole-3(2H)-carboxylate (0.30 g, 0.84 mmol) in DMF (5 mL). After 25 min, β-bromophenetole was added (0.23 mL). The reaction was quenched with saturated aqueous NH4Cl after 18 h and extracted with EtOAc (3×15 mL). The combined organic extracts were washed with brine, dried over Na2SO4, decanted, and concentrated. The crude product was purified by column chromatography (Biotage, 40S) with heptane/EtOAc (9:1) to give 0.36 g (90%) of a white solid: mp 131.5-133.0° C.; 1H NMR (300 MHz, CDCl3) δ 7.04 (d, J=1.7 Hz, 1H), 6.94 (t, J=7.4 Hz, 1H), 6.77 (m, 2H), 4.41 (m, 2H), 4.16 (m, 2H), 3.76 (m, 2H), 3.65 (m, 2H), 3.45 (m, 2H), 3.11 (m, 2H), 1.48 (s, 9H); IR (diffuse reflectance) 2974, 2929, 1691, 1600, 1496, 1459, 1413, 1393, 1365, 1348, 1303, 1243, 1170, 1114, 754 cm−1; MS (EI) m/z 474 (M+), 420, 419, 418, 417, 344, 334, 332, 57, 56; Anal. Calcd for C25H28Cl2N2O3: C, 63.16; H, 5.94; N, 5.89; found: C, 63.19; H, 5.99; N, 5.89.
Reaction SMILES: [Cl:1][C:2]1[CH:9]=[C:8]([Cl:10])[CH:7]=[CH:6][C:3]=1[CH:4]=O.[NH2:11][C@H:12]([C:20]([OH:22])=[O:21])[CH2:13][C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1.O.[OH-].[Na+:25]>C(O)C>[Cl:1][C:2]1[CH:9]=[C:8]([Cl:10])[CH:7]=[CH:6][C:3]=1[CH:4]=[N:11][CH:12]([CH2:13][C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)[C:20]([O-:22])=[O:21].[Na+:25]
Reactant: N[C@@H](Cc1ccccc1)C(=O)O
Reactant: O=Cc1ccc(Cl)cc1Cl
Agent: [Na+]
Agent: [OH-]
Solvent: CCO
Solvent: O
Product: O=C([O-])C(Cc1ccccc1)N=Cc1ccc(Cl)cc1Cl

Procedure:
A solution of 18.5 grams of 2,4-dichlorobenzaldehyde in 50 milliliters of ethanol was added to a solution of 16.5 grams of phenylalanine in about 50 milliliters of alcoholic sodium hydroxide (prepared from 4 grams of sodium hydroxide in 50 milliliters of 1:1 water:ethanol) to obtain sodium 2-(2,4-dichlorobenzalamino)-3-phenylpropionate (Schiff base) and water by-product in the reaction mixture. The solvent was evaporated and the residue was redissolved in ethanol and evaporatively distilled to remove the water in rotary evaporator. The vessel was flushed four times with 100 milliliter portions of toluene to obtain the Schiff base in a solid mixture.
Reaction SMILES: [CH3:1][Si:2]([C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1)([CH:5]=[CH2:6])[CH:3]=[CH2:4].C12CCCC(CCC1)B12[H]B2(C3CCCC2CCC3)[H]1.[OH2:33].[OH:34]O>C1COCC1>[OH:33][CH2:6][CH2:5][Si:2]([CH3:1])([C:7]1[CH:8]=[CH:9][CH:10]=[CH:11][CH:12]=1)[CH2:3][CH2:4][OH:34]
Reactant: OO
Reactant: C=C[Si](C)(C=C)c1ccccc1
Reactant: O
Solvent: C1CCOC1
Product: C[Si](CCO)(CCO)c1ccccc1
Temperature: 0 °C

Procedure:
16.1 g of methyl-phenyl-divinyl-silane is put in 65 ml of anhydrous THF under nitrogen at room temperature. 24.6 g of 9-BBN dimer is added and the mixture is refluxed for 4 h. On return to room temperature, 40 ml of H2O is added, followed by 90 ml of a 3N soda solution. The mixture is cooled to 0° C. and 90 ml of a 30% solution of hydrogen peroxide is added cautiously. The mixture is then refluxed for 2 h. The two-phase mixture is extracted with ethyl acetate three times. The organic phases are combined, washed with a saturated aqueous solution of sodium chloride, dried over magnesium sulfate and concentrated under vacuum. The raw product obtained is chromatographed on silica gel, eluting with a gradient of ethanol and of dichloromethane in heptane ranging from 0.4/3.6/6 to 0.4/4.4/5. 15.1 g of 2-[(2-hydroxy-ethyl)-methyl-phenyl-silanyl]-ethyl alcohol is obtained in the form of a white solid.
Reaction SMILES: [CH3:1][C:2]([C:4]1[CH:5]=[CH:6][C:7]([OH:10])=[CH:8][CH:9]=1)=[O:3].F[C:12]1[CH:17]=[CH:16][C:15]([C:18]([F:21])([F:20])[F:19])=[CH:14][CH:13]=1.FC1C=CC(OC2C=CC(C(=O)C)=CC=2)=CC=1>>[F:19][C:18]([F:21])([F:20])[C:15]1[CH:16]=[CH:17][C:12]([O:10][C:7]2[CH:8]=[CH:9][C:4]([C:2](=[O:3])[CH3:1])=[CH:5][CH:6]=2)=[CH:13][CH:14]=1
Reactant: CC(=O)c1ccc(O)cc1
Reactant: Fc1ccc(C(F)(F)F)cc1
Agent: CC(=O)c1ccc(Oc2ccc(F)cc2)cc1
Product: CC(=O)c1ccc(Oc2ccc(C(F)(F)F)cc2)cc1

Procedure:
1H NMR (DMSO-d6): δ15.0 (bs, 2H), 9.25 (s, 1H), 8.18 (s, 1H), 7.98 (d, J=8.4 Hz, 2H), 7.77 (d, J=9.0 Hz, 2H), 7.29 (d, J=8.7 Hz, 2H), 7.21 (d, J=8.7 Hz, 2H); mp 230-232° C. The intermediate 1-[4-(4-trifluoromethylphenoxy)phenyl]ethanone was prepared from 4-hydroxyacetophenone and 4-fluorobenzotrifluoride using the method described for the synthesis of 1-[4-(4-fluorophenoxy)phenyl]ethanone.