Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][C@H:2]([NH:11][CH3:12])[C@@H:3]([OH:10])[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.C(N(CC)CC)C.[Cl:20][CH2:21][CH2:22][CH2:23][CH2:24][C:25](Cl)=[O:26].O>C1COCC1>[Cl:20][CH2:21][CH2:22][CH2:23][CH2:24][C:25]([N:11]([C@@H:2]([CH3:1])[C@@H:3]([OH:10])[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1)[CH3:12])=[O:26]
Reactant: O=C(Cl)CCCCCl
Reactant: CN[C@@H](C)[C@@H](O)c1ccccc1
Solvent: C1CCOC1
Solvent: CCN(CC)CC
Solvent: O
Product: C[C@@H]([C@@H](O)c1ccccc1)N(C)C(=O)CCCCCl
Temperature: 0 °C
Reaction time: 0.5 h
Yield: 93.4 %

Procedure:
To a magnetically stirred solution of (1S,2S)-pseudoephedrine (60 g, 363.1 mmol) in THF (600 mL) at room temperature was added triethylamine (65.4 mL, 472 mmol) in one portion. The resulting white suspension was cooled to 0° C. A solution of 5-chloropentanoyl chloride (49 mL, 381 mmol) in THF (130 mL) was added dropwise to the mixture over 45 min using an addition funnel. The mixture was then allowed to stir at 0° C. for 30 min. H2O (40 mL) was added and the resulting mixture was concentrated to ˜10% of the original volume. The resulting solution was partitioned between H2O/EtOAc and the layers were separated. The aqueous layer was extracted with EtOAc (600 mL). The combined organic layers were washed with saturated aqueous NaHCO3, brine, dried over MgSO4, filtered, and concentrated under reduced pressure to furnish the crude product as pale yellow oil. The crude amide was purified by flash chromatography (ISCO; 3×330 g column; CH2Cl2 to 5% MeOH/CH2Cl2) to provide the product as a clear, viscous oil. The residual MeOH was removed through azeotroping with toluene (3×100 mL) to provide 5-chloro-N-((1S,2S)-1-hydroxy-1-phenylpropan-2-yl)-N-methylpentanamide (96.2 g, 339 mmol, 93%). LCMS (m/z=266.0)
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[CH:4][N:5]([CH3:27])[C:6]2[C:7]=1[CH:8]=[CH:9][C:10]1[N:19]([C:20]3[CH:25]=[CH:24][C:23]([F:26])=[CH:22][CH:21]=3)[CH2:18][CH:17]=[C:12]3[NH:13][C:14](=[O:16])[C:15]=2[C:11]=13.C(N(CC)C(C)C)(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[N:61]1([CH2:67][CH2:68][C:69](O)=[O:70])[CH2:66][CH2:65][CH2:64][CH2:63][CH2:62]1>CN(C)C(=O)C>[F:26][C:23]1[CH:22]=[CH:21][C:20]([N:19]2[C:10]3=[C:11]4[C:15](=[C:6]5[N:5]([CH3:27])[CH:4]=[CH:3][C:2]([NH:1][C:69](=[O:70])[CH2:68][CH2:67][N:61]6[CH2:66][CH2:65][CH2:64][CH2:63][CH2:62]6)=[C:7]5[CH:8]=[CH:9]3)[C:14](=[O:16])[NH:13][C:12]4=[CH:17][CH2:18]2)=[CH:25][CH:24]=1
Reactant: O=C(O)CCN1CCCCC1
Reactant: CN1C=CC(N)=c2ccc3c4c([nH]c(=O)c-4c21)=CCN3c1ccc(F)cc1
Agent: CN(C)C(On1nnc2cccnc21)=[N+](C)C
Agent: F[P-](F)(F)(F)(F)F
Solvent: CC(=O)N(C)C
Solvent: CCN(C(C)C)C(C)C
Product: CN1C=CC(NC(=O)CCN2CCCCC2)=c2ccc3c4c([nH]c(=O)c-4c21)=CCN3c1ccc(F)cc1
Yield: 4 %

Procedure:
A stock solution of Example 23e and N,N-diisopropylethylamine (0.165 M and 0.47 M in N,N-dimethylacetamide, respectively, 275 μL, 0.042 mmol Example 23e and 0.13 mmol N,N-diisopropylethylamine), 2-(3H-[1,2,3]triazolo[4,5-b]pyridin-3-yl)-1,1,3,3-tetramethylisouronium hexafluorophosphate(V) (0.25 M in N,N-dimethylacetamide, 253 μL, 0.063 mmol), and 3-(piperidin-1-yl)propanoic acid (0.40 M in N,N-dimethylacetamide, 125 μL, 0.05 mmol) were aspirated from their respective source vials, mixed through a perfluoroalkoxy mixing tube (0.2 mm inner diameter), and loaded into an injection loop. The reaction segment was injected into the flow reactor (Hastelloy coil, 0.75 mm inner diameter, 1.8 mL internal volume) set at 100° C., and passed through the reactor at 180 μL min−1 (10 minute residence time). Upon exiting the reactor, the reaction mixture was loaded directly into an injection loop and purified using reverse phase HPLC(C8, acetonitrile/water (0.1% ammonium acetate), 5-100%) to give 0.0009 g (4%) of the title compound. 1H NMR (400 MHz, DMSO-d6/D2O) δ 8.03 (d, J=2.44 Hz, 1H), 7.56 (s, 1H), 7.38 (dd, J=8.54, 2.44 Hz, 1H), 7.16 (d, J=8.54 Hz, 1H), 6.97 (s, 1H), 6.78 (m, J=8.85, 8.85 Hz, 2H), 6.51 (m, J=9.31, 4.43 Hz, 2H), 4.59 (m, 2H), 4.06 (s, 3H), 2.71 (s, 1H), 2.67 (m, 3H), 2.44 (m, 4H), 1.54 (m, 4H), 1.43 (m, 2H). MS (APCI+) m/z 500.2 (M+H)+.
Reaction SMILES: CC([S@@]([NH:7][C@@:8]1([C:18]2[CH:27]=[CH:26][C:25]3[C:20](=[CH:21][CH:22]=[CH:23][CH:24]=3)[CH:19]=2)[C:13]2=[N:14][CH:15]=[CH:16][CH:17]=[C:12]2[O:11][CH2:10][CH2:9]1)=O)(C)C.[ClH:28].O1CCOCC1>CCO>[ClH:28].[CH:19]1[C:20]2[C:25](=[CH:24][CH:23]=[CH:22][CH:21]=2)[CH:26]=[CH:27][C:18]=1[C@:8]1([NH2:7])[C:13]2=[N:14][CH:15]=[CH:16][CH:17]=[C:12]2[O:11][CH2:10][CH2:9]1
Reactant: CC(C)(C)[S@](=O)N[C@]1(c2ccc3ccccc3c2)CCOc2cccnc21
Agent: Cl
Solvent: C1COCCO1
Solvent: CCO
Product: N[C@]1(c2ccc3ccccc3c2)CCOc2cccnc21
Temperature: 25 °C
Reaction time: 1 h

Procedure:
To a solution of (S)-2-methyl-N—((S)-4-(naphthalen-2-yl)-3,4-dihydro-2H-pyrano[3,2-b]pyridin-4-yl)propane-2-sulfinamide (45 mg, 0.118 mmol) in EtOH (0.4 mL) was added 4M HCl in 1,4-dioxane (0.059 mL, 0.237 mmol). The mixture was stirred at room temperature for 1 h. The mixture was concentrated and dried in vacuo to give the title compound, which was used in the next step without further purification. MS (ESI, positive ion) m/z: 277.1 (M+H).
Reaction SMILES: [H-].[Na+].[N:3]1[C:12]2[C:7](=[CH:8][CH:9]=[CH:10][C:11]=2[NH:13][CH:14]=O)[CH:6]=[CH:5][CH:4]=1.Cl[C:17]1[CH:22]=[CH:21][CH:20]=C[C:18]=1[N+:23]([O-:25])=[O:24].O>CN(C=O)C>[N+:23]([C:18]1[CH:17]=[CH:22][CH:21]=[CH:20][C:14]=1[NH:13][C:11]1[CH:10]=[CH:9][CH:8]=[C:7]2[C:12]=1[N:3]=[CH:4][CH:5]=[CH:6]2)([O-:25])=[O:24]
Reactant: O=CNc1cccc2cccnc12
Reactant: O=[N+]([O-])c1ccccc1Cl
Agent: [H-]
Agent: [Na+]
Solvent: O
Solvent: CN(C)C=O
Product: O=[N+]([O-])c1ccccc1Nc1cccc2cccnc12
Temperature: 25 °C
Reaction time: 1 h
Yield: 21.2 %

Procedure:
A dispersion of sodium hydride in mineral oil (0.261 mol) was added portionwise at room temperature under N2 flow to a mixture of N-8-quinolinylformamide (0.174 mol) in DMF (500 ml). The mixture was stirred at room temperature for 1 hour. A solution of 1-chloro-2-nitrobenzene (0.53 mol) in DMF (200 ml) was added dropwise. The mixture was stirred at 140° C. for 12 hours and then brought to room temperature. H2O was added and the mixture was extracted with CH2Cl2. The organic layer was separated, dried (MgSO4), filtered and the solvent was evaporated. The residue (110 g) was purified by column chromatography over silica gel (eluent: CH2Cl2/cyclohexane 80/20; 20–45 elm). The pure fractions were collected and the solvent was evaporated, yielding 9.8 g (21%) of N-(2-nitrophenyl)-8-quinolinamine (interm. 23).
Reaction SMILES: [CH:1]1([C:4]([OH:6])=O)[CH2:3][CH2:2]1.[CH:7]1([CH2:10][NH2:11])[CH2:9][CH2:8]1.Cl.CN(C)CCCN=C=NCC.ON1C2C=CC=CC=2N=N1>CN(C)C=O.C(OCC)(=O)C>[CH:7]1([CH2:10][NH:11][C:4]([CH:1]2[CH2:3][CH2:2]2)=[O:6])[CH2:9][CH2:8]1
Reactant: NCC1CC1
Reactant: O=C(O)C1CC1
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Agent: On1nnc2ccccc21
Solvent: CN(C)C=O
Solvent: CCOC(C)=O
Product: O=C(NCC1CC1)C1CC1
Temperature: 25 °C
Reaction time: 20 h
Yield: 41.7 %

Procedure:
To a solution of cyclopropane carboxylic acid (1.72 g, 20 mmol) and cyclopropylmethylamine (1.42 g, 20 mmol) in N,N-dimethylformamide (20 mL) were added 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (4.22 g, 22 mmol) and 1-hydroxybenzotriazole (4.05 mmol, 30 mmol), and the mixture was stirred at room temperature for 20 hours. To the reaction solution was added ethyl acetate, and the mixture was washed with 1M hydrochloric acid and saturated aqueous sodium bicarbonate. The organic layer was dried over anhydrous magnesium sulfate, and then filtered and concentrated. The resulting residue was recrystallized (diethyl ether-n-hexane) to give the titled compound (1.16 g, 42%).
Reaction SMILES: Cl[CH2:2][C:3]([NH:5][C:6]1[CH:26]=[CH:25][C:9]2[N:10]=[C:11]([NH:14][C@H:15]3[C:24]4[C:19](=[CH:20][CH:21]=[CH:22][CH:23]=4)[CH2:18][CH2:17][CH2:16]3)[O:12][CH2:13][C:8]=2[CH:7]=1)=[O:4].[NH2:27][CH2:28][C:29]([CH3:32])([OH:31])[CH3:30]>C(#N)C>[OH:31][C:29]([CH3:32])([CH3:30])[CH2:28][NH:27][CH2:2][C:3]([NH:5][C:6]1[CH:26]=[CH:25][C:9]2[N:10]=[C:11]([NH:14][C@H:15]3[C:24]4[C:19](=[CH:20][CH:21]=[CH:22][CH:23]=4)[CH2:18][CH2:17][CH2:16]3)[O:12][CH2:13][C:8]=2[CH:7]=1)=[O:4]
Reactant: CC(C)(O)CN
Reactant: O=C(CCl)Nc1ccc2c(c1)COC(N[C@@H]1CCCc3ccccc31)=N2
Solvent: CC#N
Product: CC(C)(O)CNCC(=O)Nc1ccc2c(c1)COC(N[C@@H]1CCCc3ccccc31)=N2
Yield: 88 %

Procedure:
Prepared from 2-chloro-N-{2-[(R)-(1,2,3,4-tetrahydro-naphthalen-1-yl)amino]-4H-benzo[d][1,3]oxazin-6-yl}-acetamide (Example 38 step A) (150 mg, 0.406 mmol, HPLC 1.185 min) and 1-amino-2-methyl-propan-2-ol (723 mg, 8.1 mmol) in acetonitrile (3 ml) according to the procedure described for Example 3 step B. Obtained the title compound as an off-white solid (151 mg, 88%, HPLC 0.563 min), MS (ISP) m/e=423.3 [(M+H)+].
Reaction SMILES: [N:1]([C@H:4]([C@H:8]([N:11]=[N+]=[N-])[CH2:9][OH:10])[CH2:5][CH2:6][OH:7])=[N+]=[N-]>C(O)C.[Pt](=O)=O>[NH2:1][C@H:4]([C@H:8]([NH2:11])[CH2:9][OH:10])[CH2:5][CH2:6][OH:7]
Reactant: [N-]=[N+]=N[C@@H](CCO)[C@@H](CO)N=[N+]=[N-]
Agent: O=[Pt]=O
Solvent: CCO
Product: N[C@H](CO)[C@@H](N)CCO

Procedure:
A 10 g portion of 3,4-diazido-2,3,4-trideoxy-D-erythro-pentitol, dibenzeate was dissolved in 35 ml of ethanol, a 1.8 g portion of platinum dioxide added and the mixture reduced in a Parr shaker overnight. The catalyst was removed by filtration and the filtrate evaporated to dryness, giving 4.36 g of 3,4-diamino-2,3,4-trideoxy-D-erythro-pentitol, 1,5-dibenzerate.
Reaction SMILES: [CH2:1]([C:8]1[C:9]([C:15]#[C:16][C:17]2([OH:25])[CH:22]3[CH2:23][CH2:24][N:19]([CH2:20][CH2:21]3)[CH2:18]2)=[N:10][CH:11]=[C:12](Br)[CH:13]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[N:26]1[CH:31]=[CH:30][CH:29]=[CH:28][C:27]=1[Sn](CCCC)(CCCC)CCCC>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.C1(C)C=CC=CC=1>[CH2:1]([C:8]1[C:9]([C:15]#[C:16][C:17]2([OH:25])[CH:22]3[CH2:23][CH2:24][N:19]([CH2:20][CH2:21]3)[CH2:18]2)=[N:10][CH:11]=[C:12]([C:27]2[CH:28]=[CH:29][CH:30]=[CH:31][N:26]=2)[CH:13]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: CCCC[Sn](CCCC)(CCCC)c1ccccn1
Reactant: OC1(C#Cc2ncc(Br)cc2Cc2ccccc2)CN2CCC1CC2
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Solvent: Cc1ccccc1
Product: OC1(C#Cc2ncc(-c3ccccn3)cc2Cc2ccccc2)CN2CCC1CC2
Reaction time: 2 h
Yield: 67 %

Procedure:
A mixture of 150 mg of 3-(3-benzyl-5-bromo-2-pyridyl)ethynyl-3-quinuclidinol, 150 mg of (2-pyridyl)tributyltin, 86 mg of tetrakis(triphenylphosphine)palladium(0) and 3.5 ml of toluene was heated under stirring in an oil bath kept at 110° C. for 2 hours in a nitrogen atmosphere. After cooling as it was, NH-silica gel was added to the reaction solution and the solvent was removed. The residue was subjected to NH-silica gel column chromatography using 2.5% methanol/ethyl acetate, to give 100 mg of the target compound.
Reaction SMILES: Br[C:2]1[CH:3]=[C:4]([C:8](=[N:10][C:11]2[C:16]([CH:17]([CH3:19])[CH3:18])=[CH:15][CH:14]=[CH:13][C:12]=2[CH:20]([CH3:22])[CH3:21])[CH3:9])[CH:5]=[CH:6][CH:7]=1.[Li]CCCC.Br[C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][C:30]=1[O:35][CH3:36].O>C1COCC1.[Cl-].[Cl-].[Zn+2].CC(C)([P](C(C)(C)C)([Pd][P](C(C)(C)C)(C(C)(C)C)C(C)(C)C)C(C)(C)C)C>[CH:20]([C:12]1[CH:13]=[CH:14][CH:15]=[C:16]([CH:17]([CH3:19])[CH3:18])[C:11]=1[N:10]=[C:8]([C:4]1[CH:3]=[C:2]([C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][C:30]=2[O:35][CH3:36])[CH:7]=[CH:6][CH:5]=1)[CH3:9])([CH3:22])[CH3:21]
Reactant: CC(=Nc1c(C(C)C)cccc1C(C)C)c1cccc(Br)c1
Reactant: COc1ccccc1Br
Agent: CC(C)(C)[P]([Pd][P](C(C)(C)C)(C(C)(C)C)C(C)(C)C)(C(C)(C)C)C(C)(C)C
Agent: [Cl-]
Agent: [Li]CCCC
Solvent: O
Solvent: C1CCOC1
Product: COc1ccccc1-c1cccc(C(C)=Nc2c(C(C)C)cccc2C(C)C)c1
Temperature: -70 °C
Reaction time: 1 h
Yield: 79 %

Procedure:
To a solution of 2.78 g (7.75 mmol) of 13 in 30 mL of THF, 3.10 mL (7.75 mmol) of 2.5 M nBuLi in hexanes was added at −100° C. The reaction mixture was stirred for 1 hr at −70° C., then cooled to −100° C., and 8.35 mL (8.35 mmol) of 1M ZnCl2 in THF was added. The resulting mixture was slowly warmed to room temperature, stirred for 12 hr at this temperature, and then 1.45 g (7.75 mmol) of 2-bromoanisole and 85 mg (0.15 mmol) of Pd(PtBu3)2 were added. The resulting mixture was refluxed for 3 hr, and then 5 mL of water was added. This mixture was passed through short layer of silica gel 60 (40-63 um) which was then additionally washed with 30 mL of dichloromethane. The combined organic filtrate was evaporated to dryness, and the product was isolated by flash chromatography on silica gel 60(40-63 um, eluent: from hexanes to hexanes-diethyl ether=20:1, vol.). This procedure gave 2.36 g (79%) of the title product.
Reaction SMILES: [CH3:1][N:2]1[CH2:7][CH2:6][CH:5]([CH2:8][C:9]2[CH:10]=[C:11]([C:15]3[CH:20]=[CH:19][CH:18]=[C:17]([CH2:21][NH2:22])[CH:16]=3)[CH:12]=[CH:13][CH:14]=2)[CH2:4][CH2:3]1.Cl[S:24]([C:27]1[CH:28]=[C:29]([CH:33]=[CH:34][CH:35]=1)[C:30]([OH:32])=[O:31])(=[O:26])=[O:25]>C(Cl)Cl>[CH3:1][N:2]1[CH2:7][CH2:6][CH:5]([CH2:8][C:9]2[CH:10]=[C:11]([C:15]3[CH:20]=[CH:19][CH:18]=[C:17]([CH2:21][NH:22][S:24]([C:27]4[CH:28]=[C:29]([CH:33]=[CH:34][CH:35]=4)[C:30]([OH:32])=[O:31])(=[O:26])=[O:25])[CH:16]=3)[CH:12]=[CH:13][CH:14]=2)[CH2:4][CH2:3]1
Reactant: O=C(O)c1cccc(S(=O)(=O)Cl)c1
Reactant: CN1CCC(Cc2cccc(-c3cccc(CN)c3)c2)CC1
Solvent: ClCCl
Product: CN1CCC(Cc2cccc(-c3cccc(CNS(=O)(=O)c4cccc(C(=O)O)c4)c3)c2)CC1
Yield: 89.9 %

Procedure:
To a solution of 1-{3′-[(1-methyl-4-piperidinyl)methyl]-3-biphenylyl}methanamine (0.0589 g, 0.2 mmol) in DCM (2 mL) was added TEA (0.0606 mL, 0.4 mmol) and then 3-(chlorosulfonyl)benzoic acid (0.0441 g, 0.2 mmol) whereupon the reaction was stirred at room temperature for 17 h. The reaction mixture was concentrated on a Glas-Col evaporator, purified using a Gilson HPLC (with 0.1% TFA), and concentrated to afford 0.0861 g (57%) of the title compound. LC-MS m/z 479 (M+H)+.
Reaction SMILES: [CH2:1]([NH2:4])[CH:2]=[CH2:3].CS(O[CH2:10][C@H:11]([NH:13][S:14]([C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=1[N+:23]([O-:25])=[O:24])(=[O:16])=[O:15])[CH3:12])(=O)=O>O1CCCC1>[CH2:1]([NH:4][CH2:12][C@H:11]([NH:13][S:14]([C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=1[N+:23]([O-:25])=[O:24])(=[O:16])=[O:15])[CH3:10])[CH:2]=[CH2:3]
Reactant: C[C@H](COS(C)(=O)=O)NS(=O)(=O)c1ccccc1[N+](=O)[O-]
Reactant: C=CCN
Solvent: C1CCOC1
Product: C=CCNC[C@@H](C)NS(=O)(=O)c1ccccc1[N+](=O)[O-]
Temperature: 80 °C
Reaction time: 16 h

Procedure:
5.4 mL of allylamine was added to a tetrahydrofuran (100 mL) solution of 8.2 g of (R)-2-(2-nitrophenylsulfonamido)propyl methanesulfonate, and the mixture was stirred at 80° C. for 16 hours. After the completion of reaction, the reaction solution was returned to room temperature, and 100 mL of saturated saline was added thereto. From this mixed solution, two extractions were performed with 100 mL of ethyl acetate. The extract was dried over anhydrous sodium sulfate. After filtration, the filtrate was concentrated, and the obtained crude product was purified by silica gel column chromatography (ethyl acetate:hexane=1:1) to obtain 7 g of the compound of interest as a yellow oil (96%).
Reaction SMILES: [OH:1][C:2]1[CH:9]=[C:8]([O:10][CH2:11][C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[CH:7]=[CH:6][C:3]=1[CH:4]=O.[N+:18](CC)([O-])=O.C([O-])(=O)C.[Na+].O>C(O)(=O)C>[OH:1][C:2]1[CH:9]=[C:8]([O:10][CH2:11][C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[CH:7]=[CH:6][C:3]=1[C:4]#[N:18]
Reactant: CC[N+](=O)[O-]
Reactant: O=Cc1ccc(OCc2ccccc2)cc1O
Agent: CC(=O)[O-]
Agent: [Na+]
Solvent: O
Solvent: CC(=O)O
Product: N#Cc1ccc(OCc2ccccc2)cc1O
Yield: 52.4 %

Procedure:
A mixture of 226 g (1.00 mol) of 2-hydroxy-4(phenylmethoxy)benzaldehyde in 287 ml (3.83 mol) of nitroethane and of 313 g (2.3 mol) of sodium acetate in 570 ml of acetic acid is heated at 104° C. for 8 hours and is then poured into 3 l of a mixture of water and ice. The precipitate is then filtered off, rinsed with diisopropyl ether and dried. 118 g of product are obtained. Moreover, the filtrate is extracted with diethyl ether, the organic phase is washed with an aqueous sodium hydrogencarbonate solution and then with water, dried over sodium sulphate and concentrated under reduced pressure and the residue is then triturated in diisopropyl ether. 67 additional g of product are thus obtained.
Reaction SMILES: C1(C(C2C=CC=CC=2)(C2C=CC=CC=2)[NH:8][CH2:9][CH2:10][S:11][C:12](OC2C=CC([N+]([O-])=O)=CC=2)=[O:13])C=CC=CC=1.[NH2:36][CH2:37][CH2:38][C:39]1[CH:44]=[CH:43][CH:42]=[CH:41][N:40]=1>>[N:40]1[CH:41]=[CH:42][CH:43]=[CH:44][C:39]=1[CH2:38][CH2:37][NH:36][C:12]([S:11][CH2:10][CH2:9][NH2:8])=[O:13]
Reactant: NCCc1ccccn1
Reactant: O=C(Oc1ccc([N+](=O)[O-])cc1)SCCNC(c1ccccc1)(c1ccccc1)c1ccccc1
Product: NCCSC(=O)NCCc1ccccn1

Procedure:
N-triphenylmethyl-2-paranitrophenoxycarbonylthioethylamine (500 mg) and 2-(2-aminoethyl)pyridine (375 μl) were subjected to the reactions described in References 2 and 4 to give 2-(2-pyridyl)ethylaminocarbonylthioethylamine (crude formate: 218 mg). The product (190 mg) was dissolved in anhydrous methanol (3 ml), to which were then added triethylamine (490 μl) and mitomycin A (245 mg: 1.0 molar equivalent). The reaction solution was treated in a similar manner to that described in Example 1 to obtain Compound 49 (297 mg) in the form of grayish blue powders with a yield of 78%.
Reaction SMILES: [CH2:1]1[CH:5]2[CH:6]3C=CC([CH:4]2[CH:3]=[CH:2]1)C3.C[SiH:12]([Cl:14])[Cl:13].CCCCCCCCCCCCCCCC>[Pd].C(P(CCCC)CCCC)CCC.C1(C)C=CC=CC=1>[CH:5]1([CH2:6][SiH:12]([Cl:14])[Cl:13])[CH2:4][CH2:3][CH:2]=[CH:1]1
Reactant: C[SiH](Cl)Cl
Reactant: C1=CC2C3C=CC(C3)C2C1
Agent: [Pd]
Agent: CCCCP(CCCC)CCCC
Solvent: CCCCCCCCCCCCCCCC
Solvent: Cc1ccccc1
Product: Cl[SiH](Cl)CC1C=CCC1
Reaction time: 1 h
Yield: 319.8 %

Procedure:
As described in Example 2, 2.92 g (0.0221 mol) of dicyclopentadiene, 3.79 g (0.0331 mol) of methyldichlorosilane, 0.0602 g 1% Pd on Charcoal, 86 μL (0.000267 mol) of tributylphosphine and 4 mL of toluene and 2 mL of hexadecane were placed in a reactor. The reactor was sealed and the reaction was performed at 180° C. for 1 hour. Products were subject to simple vacuum distillation, thereby providing a mixture (12.8 g) of (2-cyclopentenyl)methyldichlorosilane (3.8 g, 63%), other unreacted reactants, toluene, hexadecane, and unidentified compounds. Besides, tetrakis(triphenylphosphine)palladium also showed catalyst effect.
Reaction SMILES: [CH3:1][N:2]1[CH:6]=[C:5](/[CH:7]=[CH:8]/[C:9]([O:11]CC)=[O:10])[CH:4]=[N:3]1.CO.[OH-].[Na+].Cl>O1CCCC1>[CH3:1][N:2]1[CH:6]=[C:5](/[CH:7]=[CH:8]/[C:9]([OH:11])=[O:10])[CH:4]=[N:3]1
Reactant: CCOC(=O)/C=C/c1cnn(C)c1
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: C1CCOC1
Solvent: CO
Product: Cn1cc(/C=C/C(=O)O)cn1
Temperature: 60 °C
Reaction time: 3 h
Yield: 82.9 %

Procedure:
To a mixture of ethyl (2E)-3-(1-methyl-1H-pyrazol-4-yl)acrylate (2.5 g), methanol (20 ml) and tetrahydrofuran (20 ml) was added a 2N aqueous sodium hydroxide solution (13.9 ml) and the mixture was stirred at 60° C. for 3 hrs. 1N Hydrochloric acid was poured into the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was washed with water, dried over anhydrous magnesium sulfate, and concentrated to give (2E)-3-(1-methyl-1H-pyrazol-4-yl)acrylic acid (1.75 g, 83%) as an amorphous form.
Reaction SMILES: [CH:1]([N:4]1[CH2:9][CH2:8][N:7]([C:10]([C:12]2[CH:19]=[CH:18][C:15]([CH:16]=O)=[CH:14][CH:13]=2)=[O:11])[CH2:6][CH2:5]1)([CH3:3])[CH3:2].[NH:20]1[CH2:25][CH2:24][O:23][CH2:22][CH2:21]1.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+]>C1COCC1>[CH:1]([N:4]1[CH2:9][CH2:8][N:7]([C:10]([C:12]2[CH:19]=[CH:18][C:15]([CH2:16][N:20]3[CH2:25][CH2:24][O:23][CH2:22][CH2:21]3)=[CH:14][CH:13]=2)=[O:11])[CH2:6][CH2:5]1)([CH3:3])[CH3:2]
Reactant: C1COCCN1
Reactant: CC(C)N1CCN(C(=O)c2ccc(C=O)cc2)CC1
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: [Na+]
Solvent: C1CCOC1
Product: CC(C)N1CCN(C(=O)c2ccc(CN3CCOCC3)cc2)CC1
Temperature: 25 °C
Reaction time: 0.25 h

Procedure:
To a solution of 4-(4-isopropyl-piperazine-1-carbonyl)-benzaldehyde (32.0 g, 123 mmol) in THF (650 mL) was added morpholine (21.4 g, 246 mmol), in a slow stream via an addition funnel over 15 min, and the resulting mixture was stirred at room temperature for 40 min. The reaction mixture was treated with NaBH(OAc)3 (38.4 g, 172 mmol) in portions over 40 min, was stirred at room temperature for 16 h, and then concentrated to a residue. The residue was diluted with EtOAc (400 mL), cooled to 0° C., and treated with 1 N NaOH (250 mL). The biphasic solution stirred at 0° C. for 30 min. The phases were separated and the aqueous layer was extracted with EtOAc (2×200 mL) and CH2Cl2 (2×100 mL). The organic layers were combined, washed with brine (1×300 mL), dried (Na2SO4), and concentrated to yield the title compound as a pale yellow oil.
Reaction SMILES: [O:1]([CH2:5][CH2:6][NH2:7])[N+:2]([O-:4])=[O:3].[F:8][C:9]1[CH:10]=[C:11]2[C@:18]3([C:22](=[O:23])[NH:21][C:20](=[O:24])[NH:19]3)[CH2:17][C@@H:16]([C:25](Cl)=[O:26])[O:15][C:12]2=[CH:13][CH:14]=1>>[O:1]([CH2:5][CH2:6][NH:7][C:25]([C@@H:16]1[CH2:17][C@@:18]2([C:22](=[O:23])[NH:21][C:20](=[O:24])[NH:19]2)[C:11]2[C:12](=[CH:13][CH:14]=[C:9]([F:8])[CH:10]=2)[O:15]1)=[O:26])[N+:2]([O-:4])=[O:3]
Reactant: NCCO[N+](=O)[O-]
Reactant: O=C1NC(=O)[C@@]2(C[C@@H](C(=O)Cl)Oc3ccc(F)cc32)N1
Product: O=C1NC(=O)[C@@]2(C[C@@H](C(=O)NCCO[N+](=O)[O-])Oc3ccc(F)cc32)N1
Yield: 82.3 %

Procedure:
The procedure similar to that as described in Example 8 was carried out with use of 2-nitroxyethylamine and (2S,4S)-6-fluoro-2',5'-dioxospiro[chroman-4,4'-imidazolidine]-2-carbonyl chloride (Reference Example 1) to give the desired compound.
Reaction SMILES: [CH2:1]([NH2:4])[CH2:2][NH2:3].Cl[CH2:6][CH2:7][CH2:8][CH3:9]>>[CH2:6]([N:3]([CH2:6][CH2:7][CH2:8][CH3:9])[CH2:2][CH2:1][N:4]([CH2:6][CH2:7][CH2:8][CH3:9])[CH2:6][CH2:7][CH2:8][CH3:9])[CH2:7][CH2:8][CH3:9]
Reactant: NCCN
Reactant: CCCCCl
Product: CCCCN(CCCC)CCN(CCCC)CCCC

Procedure:
A three-necked round-bottomed flask (3 L) equipped with a Friedrich's condenser and an overhead mechanical stirrer is placed in a cooling bath. The flask is charged with dimethylformamide (DMF, 500 mL), potassium carbonate (2.1 mol), and potassium iodide (0.1 mol). The mixture is allowed to stir until the potassium iodide was dissolved (giving a faint yellow tint) and the potassium carbonate was fairly homogenized. Ethylenediamine (0.5 mol) is then added to the reaction mixture. 1-Chlorobutane (2.2 mol) is added drop-wise to the resulting reaction mixture from a pressure-equalizing addition funnel under efficient mechanical stirring. During the addition of the alkyl halide, the exothermic reaction which may occur is controlled by cooling the round-bottomed flask bath with the cooling bath so as to maintain the reaction temperature below room temperature (e.g., using a chiller temperature ˜5° C.). After all the alkyl halide has been added and any exotherm subsides, the cooling bath is replaced by a heating mantle or oil bath. The reaction mixture is then heated (˜50° C. reaction temperature; ˜70-80° C. bath temperature) under efficient stirring. After heating overnight, the reaction set-up is modified for vacuum distillation and unreacted alkyl halide and a majority of the DMF (about 400-450 mL) is removed. The resulting residual mixture in the reaction flask is partitioned between water and ethyl acetate in a separatory funnel to separate the polyalkylated product from the inorganic salts. The aqueous fraction is extracted three times with ethyl acetate and the combined ethyl acetate solutions are sequentially washed with water and brine solution. The ethyl acetate extract is dried over sodium sulfate, filtered and concentrated using a rotary evaporator. The resulting oily residue can be distilled under reduced pressure to isolate a purified fraction of tetrabutylethylenediamine.