Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Br:1][CH:2]([CH3:16])[C:3]([C:5]1[S:9][C:8]2[CH:10]=[CH:11][C:12]([Cl:15])=[C:13]([Cl:14])[C:7]=2[CH:6]=1)=O.[NH:17]1[CH2:21][CH2:20][NH:19][C:18]1=[S:22].C(O)C>C(O)(=O)C>[BrH:1].[Cl:14][C:13]1[C:7]2[CH:6]=[C:5]([C:3]3[N:19]4[CH2:20][CH2:21][N:17]=[C:18]4[S:22][C:2]=3[CH3:16])[S:9][C:8]=2[CH:10]=[CH:11][C:12]=1[Cl:15]
Reactant: CC(Br)C(=O)c1cc2c(Cl)c(Cl)ccc2s1
Reactant: S=C1NCCN1
Solvent: CCO
Solvent: CC(=O)O
Product: Br
Product: CC1=C(c2cc3c(Cl)c(Cl)ccc3s2)N2CCN=C2S1
Temperature: 25 °C
Yield: 101.3 %

Procedure:
A mixture of 2-bromo-1-(4,5-dichlorobenzo[b]thiophen-2-yl)propan-1-one (1.59 g), 2-imidazolidinethione (0.43 g), ethanol (25 ml) and acetic acid (12.5 ml) was heated under reflux for 4 hours and allowed to cool to ambient temperature. The solvent was removed in vacuo to give a yellow solid which was triturated with ether (3×10 ml). The resulting solid was collected by filtration and dried in vacuo at 60° C. to give 3-(4,5-dichlorobenzo[b]thiophen-2-yl)-2-methyl-5,6-dihydroimidazo[2,1-b]-thiazole hydrobromide (1.8 g) as a yellow solid, m.p. 244-246° C.
Reaction SMILES: [C:1]([O:4][CH:5]([C:9]1[CH:14]=[C:13]([O:15][CH3:16])[C:12]([O:17][CH3:18])=[C:11]([O:19][CH3:20])[CH:10]=1)[C:6]([OH:8])=O)(=[O:3])[CH3:2].[C:21](N1C=CN=C1)([N:23]1C=CN=[CH:24]1)=[O:22].CNC[C:36]1[CH:41]=[CH:40][C:39]2O[CH2:43][CH2:44][O:45][C:38]=2[CH:37]=1>ClCCl>[CH3:20][O:19][C:11]1[CH:10]=[C:9]([C:5]2([O:4][C:1](=[O:3])[CH3:2])[C:6]3[O:8][CH2:43][CH2:44][O:45][C:38]=3[CH:37]=[CH:36][CH:41]2[CH2:40][CH2:39][C:21]([NH:23][CH3:24])=[O:22])[CH:14]=[C:13]([O:15][CH3:16])[C:12]=1[O:17][CH3:18]
Reactant: CNCc1ccc2c(c1)OCCO2
Reactant: O=C(n1ccnc1)n1ccnc1
Reactant: COc1cc(C(OC(C)=O)C(=O)O)cc(OC)c1OC
Solvent: ClCCl
Product: CNC(=O)CCC1C=CC2=C(OCCO2)C1(OC(C)=O)c1cc(OC)c(OC)c(OC)c1
Temperature: 25 °C
Reaction time: 2 h
Yield: 92.4 %

Procedure:
A solution of α-acetoxy-3,4,5-trimethoxyphenyl-acetic acid (5.0 g) in dichloromethane (40 ml) was reacted with 1,1′-carbonyldiimidazole (2.92 g) at room temperature for 30 minutes. The solution was refluxed for 30 minutes, after which N-methyl-3,4-ethylenedioxybenzylamine (3.26 g) dissolved in dichloromethane (10 ml) was added. The mixture was stirred at room temperature for 2 hours, after which it was washed with aqueous hydrochloric acid (20 ml, 1M) followed by aqueous sodium hydrogen carbonate (20 ml, 0.5 M). The organic phase was dried and concentrated to dryness, leaving crude 2-(3,4,5-trimethoxyphenyl)-2-acetoxy-N-methyl-N-3,4-ethylenedioxybenzylacetamide (7.27 g).
Reaction SMILES: C([O:3][P:4]([CH2:9][NH:10][CH2:11][C:12]([OH:14])=[O:13])([O:6]CC)=[O:5])C>Cl>[CH2:11]([NH:10][CH2:9][P:4]([OH:6])([OH:5])=[O:3])[C:12]([OH:14])=[O:13]
Reactant: CCOP(=O)(CNCC(=O)O)OCC
Agent: Cl
Product: O=C(O)CNCP(=O)(O)O

Procedure:
Diethylphosphonomethyl glycine (6 g) was refluxed, for 16 hours, with concentrated hydrochloric acid (20 ml). The reaction mixture was cooled and the solvent was evaporated to obtain glyphosate, which was confirmed by high pressure liquid chromatograph and 31P-nuclear magnetic resonance and infrared spectra.
Reaction SMILES: [Mg].Br[C:3]1[CH:4]=[C:5]([O:9][CH3:10])[CH:6]=[CH:7][CH:8]=1.[CH2:11]([N:18]1[CH2:23][CH2:22][CH2:21][CH2:20][C:19]1=O)[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1.Cl.C1C[O:29]CC1>>[CH2:11]([N:18]1[CH2:23][CH2:22][CH2:21][C:20]([C:3]2[CH:8]=[CH:7][CH:6]=[C:5]([O:9][CH3:10])[CH:4]=2)([OH:29])[CH2:19]1)[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1
Reactant: COc1cccc(Br)c1
Reactant: O=C1CCCCN1Cc1ccccc1
Reactant: C1CCOC1
Agent: Cl
Agent: [Mg]
Product: COc1cccc(C2(O)CCCN(Cc3ccccc3)C2)c1
Temperature: 50 °C

Procedure:
4.22 g magnesium (Mg) in 50 mL THF and a speck of 12 were placed under a nitrogen atmosphere in a three-necked flask equipped with condenser, internal thermometer and dropping funnel. The mixture was heated to 50° C. while stirring and 22.1 ml of 3-bromoanisole in 50 ml THF were added dropwise within 30 minutes. The mixture was then stirred for a further 30 minutes at 70° C. After cooling with ice to 5° C., 22.34 g of N-benzyl-piperidone in 100 ml THF were added dropwise in 60 minutes. The mixture was stirred for a further 15 hours at room temperature. For the hydrolysis, 400 ml of 10% NH4HSO4 solution were added, acidified with dilute HCl, and then extracted with 100 ml of diethyl ether. The organic phase was extracted once with dilute HCl. The combined aqueous phases were made alkaline with NaOH and extracted three times with 100 ml portions of diethyl ether each time. The combined organic phases were concentrated by evaporation. Yield 35.05 g
Reaction SMILES: C(N(CC)CC)C.[CH3:8][O:9][CH2:10][CH2:11][C:12]([N:14]([C:31](=[O:36])[C:32]([F:35])([F:34])[F:33])[C:15]1[C:20]([S:21](O)(=[O:23])=[O:22])=[CH:19][CH:18]=[CH:17][C:16]=1[C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1)=[O:13].P(Cl)(Cl)(Cl)(Cl)[Cl:38]>ClCCl>[CH3:8][O:9][CH2:10][CH2:11][C:12]([N:14]([C:31](=[O:36])[C:32]([F:35])([F:34])[F:33])[C:15]1[C:20]([S:21]([Cl:38])(=[O:23])=[O:22])=[CH:19][CH:18]=[CH:17][C:16]=1[C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1)=[O:13]
Reactant: ClP(Cl)(Cl)(Cl)Cl
Reactant: COCCC(=O)N(C(=O)C(F)(F)F)c1c(-c2ccccc2)cccc1S(=O)(=O)O
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: COCCC(=O)N(C(=O)C(F)(F)F)c1c(-c2ccccc2)cccc1S(=O)(=O)Cl

Procedure:
To a solution of 3.8 g (7 mmol) of the N,N-diethylethanamine salt of 2-[(3-methoxy-1-oxopropyl)(trifluoroacetyl)amino][1,1'-biphenyl]-3-sulphonic acid in 14 ml of dichloromethane are added 1.75 g (8.4 mmol) of phosphorus pentachloride, the mixture is heated for 3 hours at the reflux temperature and is then concentrated under reduced pressure. The residue thus obtained is purified by chromatography on a column of silica gel, eluting with dichloromethane.
Reaction SMILES: [Si:1]([O:8][C:9]1[CH:10]=[C:11]([CH:14]=[C:15](/[CH:17]=[CH:18]/[CH2:19][O:20][CH3:21])[CH:16]=1)[CH:12]=[O:13])([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2]>CCOC(C)=O.[Pd]>[Si:1]([O:8][C:9]1[CH:10]=[C:11]([CH:14]=[C:15]([CH2:17][CH2:18][CH2:19][O:20][CH3:21])[CH:16]=1)[CH:12]=[O:13])([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:2])[CH3:3]
Reactant: COC/C=C/c1cc(C=O)cc(O[Si](C)(C)C(C)(C)C)c1
Agent: [Pd]
Solvent: CCOC(C)=O
Product: COCCCc1cc(C=O)cc(O[Si](C)(C)C(C)(C)C)c1
Reaction time: 1 h

Procedure:
To a solution of 3-{[tert-butyl(dimethyl)silyl]oxy}-5-[(1E)-3-methoxyprop-1-en-1-yl]benzaldehyde from Amine 36, Step 3 (1 eq.) in EtOAc (0.1 M) was added palladium (10% w/w over activated carbon, 10% loading). The vessel was evacuated and back filled with hydrogen. The reaction suspension was then stirred under a balloon atmosphere of hydrogen for 1 h. The reaction was quenched with dichloromethane and filtered through a bed of celite. The insolubles were washed further with EtOAc and methanol. Concentration of the filtrate in vacuo and purification of the crude product thus obtained by way of column chromatography (SiO2, Hex→3:2 (v/v) Hex:EtOAc) afforded the title compound as a pale yellow oil.
Reaction SMILES: [C:1]([O:9][C@@H:10]1[CH2:18][C@@H:13]2[O:14][C:15](=[O:17])[CH2:16][C@@H:12]2[C@H:11]1/[CH:19]=[CH:20]/[C:21](=[O:31])[CH2:22][O:23][C:24]1[CH:29]=[CH:28][CH:27]=[C:26]([Cl:30])[CH:25]=1)(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.B(Cl)([C@H]1[C@H](C)[C@@H]2C(C)(C)[C@@H](C2)C1)[C@H]1[C@H](C)[C@@H]2C(C)(C)[C@@H](C2)C1>C1COCC1>[C:1]([O:9][C@@H:10]1[CH2:18][C@@H:13]2[O:14][C:15](=[O:17])[CH2:16][C@@H:12]2[C@H:11]1/[CH:19]=[CH:20]/[C@@H:21]([OH:31])[CH2:22][O:23][C:24]1[CH:29]=[CH:28][CH:27]=[C:26]([Cl:30])[CH:25]=1)(=[O:8])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: O=C(/C=C/[C@@H]1[C@H]2CC(=O)O[C@H]2C[C@H]1OC(=O)c1ccccc1)COc1cccc(Cl)c1
Agent: C[C@@H]1[C@H]2C[C@@H](C[C@H]1B(Cl)[C@@H]1C[C@@H]3C[C@H]([C@H]1C)C3(C)C)C2(C)C
Solvent: C1CCOC1
Product: O=C1C[C@@H]2[C@@H](/C=C/[C@@H](O)COc3cccc(Cl)c3)[C@H](OC(=O)c3ccccc3)C[C@@H]2O1
Temperature: 25 °C
Reaction time: 4 h
Yield: 48.2 %

Procedure:
To a solution of 9.70 g (22.0 mmol) of enone 13 in 60 mL of THF at −23° C. was added dropwise a solution of 11.1 g (34.6 mmol) of (−)-B-chlorodiisopinocampheylborane in 30 mL of THF. After 4 h, the reaction was quenched by the dropwise addition of 5 mL of methanol and then warmed to room temperature. After pouring into 200 mL of a 2/1 mixture of ethyl acetate/saturated NH4Cl, the layers were separated, and the aqueous phase was extracted with ethyl acetate (2×100 mL). Combined organic layers were dried over MgSO4, filtered, concentrated, and the residue was chromatographed on silica gel eluting with ethyl acetate/hexanes, 3/2, to afford 4.7 g (48%) of 14 as a white solid, m.p. 101.0-102.5° C. 1H NMR δ 8.05-7.95 (m, 2 H), 7.62-7.40 (m, 3 H), 7.18 (t, J=8.0 Hz, 1 H), 7.0-6.92 (m, 1 H), 6.85 (t, J=2.1 Hz, 1 H), 6.77-6.70 (m, 1 H), 5.85 (d of d, J=6.2, 15.5 Hz, 1 H), 5.72 (d of d, J=4.5, 15.5 Hz, 1 H), 5.30 (q, J=5.8 Hz, 1 H), 5.12-5.04 (m, 1 H), 4.58-4.48 (m, 1 H), 3.92 (d of d, J=3.5, 9.3 Hz, 1 H), 3.80 (d of d, J=7.3, 9.4 Hz, 1 H), 2.9-2.2 (m, 8 H).
Reaction SMILES: [Cl:1][C:2]1[C:11]2[C:6](=[CH:7][C:8]([O:26][CH3:27])=[C:9]([O:12][CH2:13][CH:14]3[CH2:18][CH2:17][N:16](C(OC(C)(C)C)=O)[CH2:15]3)[CH:10]=2)[N:5]=[CH:4][N:3]=1.[Cl:28][C:29]1[C:30]([F:36])=[C:31]([CH:33]=[CH:34][CH:35]=1)[NH2:32]>>[ClH:1].[Cl:28][C:29]1[C:30]([F:36])=[C:31]([CH:33]=[CH:34][CH:35]=1)[NH:32][C:2]1[C:11]2[C:6](=[CH:7][C:8]([O:26][CH3:27])=[C:9]([O:12][CH2:13][CH:14]3[CH2:18][CH2:17][NH:16][CH2:15]3)[CH:10]=2)[N:5]=[CH:4][N:3]=1
Reactant: Nc1cccc(Cl)c1F
Reactant: COc1cc2ncnc(Cl)c2cc1OCC1CCN(C(=O)OC(C)(C)C)C1
Product: COc1cc2ncnc(Nc3cccc(Cl)c3F)c2cc1OCC1CCNC1
Product: Cl
Yield: 100 %

Procedure:
4-chloro-7-methoxy-6-{[1-(tert-butoxycarbonyl)pyrrolidin-3-yl]methoxy}quinazoline (4.5 g) was reacted with 3-chloro-2 fluoroaniline to give 4-(3-chloro-2-fluoroanilino)-7-methoxy-6-(pyrrolidin-3-ylmethoxy)quinazoline hydrochloride (5.45 g, 100%); 1H NMR Spectrum: (DMSO d6) 1.71-1.85 (m, 1H); 2.10-2.22 (m, 1H); 2.81-2.91 (m, 1H); 2.97-3.07 (m, 1H); 3.11-3.22 (m, 1H); 3.24-3.33 (m, 1H); 3.35-3.46 (m, 1H); 4.00 (s, 3H); 4.28-4.34 (m, 2H); 7.31-7.37 (m, 1H); 7.43 (s, 1H); 7.49-7.54 (m, 1H); 7.59-7.64 (m, 1H); 8.60 (s, 1H); 8.80 (s, 1H); 9.32 (bs, 2H); 12.05 (bs, 1H); Mass Spectrum: (M−H)− 401.
Reaction SMILES: [Cl:1][C:2]1[N:7]=[C:6]([NH2:8])[CH:5]=[C:4]([Cl:9])[N:3]=1.[CH2:10]([O:12][C:13](=[O:18])[C:14](=O)[CH2:15]Br)[CH3:11]>>[CH2:10]([O:12][C:13]([C:14]1[N:8]=[C:6]2[CH:5]=[C:4]([Cl:9])[N:3]=[C:2]([Cl:1])[N:7]2[CH:15]=1)=[O:18])[CH3:11]
Reactant: Nc1cc(Cl)nc(Cl)n1
Reactant: CCOC(=O)C(=O)CBr
Product: CCOC(=O)c1cn2c(Cl)nc(Cl)cc2n1

Procedure:
2,6-Dichloro-pyrimidin-4-ylamine and 3-bromo-2-oxo-propionic acid ethyl ester were reacted to provide 5,7-dichloro-imidazo[1,2-c]pyrimidine-2-carboxylic acid ethyl ester. The title compound was prepared from 5,7-dichloro-imidazo[1,2-c]pyrimidine-2-carboxylic acid ethyl ester and 5-methyl-1H-pyrazol-3-ylamine according to the procedure described in Scheme 7. 1H NMR (400 MHz, DMSO) 10.81 (s, 1H) 9.10 (s, 1H) 7.10 (s, 1H) 6.48 (s, 1H) 4.37 (q, J=7.2 Hz 2H) 2.28 (s, 3H) 1.33 (t, J=7.2 Hz, 3H). [M+H] calc'd for C13 H14ClN6O2, 321; found, 321.
Reaction SMILES: C(N(CC)CC)C.Cl.Cl.[NH2:10][C@H:11]1[CH:16]2[CH2:17][CH2:18][N:13]([CH2:14][CH2:15]2)[CH2:12]1.[CH3:19][O:20][C:21]1[CH:29]=[CH:28][CH:27]=[CH:26][C:22]=1[C:23](O)=[O:24].[I-].ClC1C=CC=C[N+]=1C>O.C(#N)C>[CH3:19][O:20][C:21]1[CH:29]=[CH:28][CH:27]=[CH:26][C:22]=1[C:23]([NH:10][C@H:11]1[CH:16]2[CH2:17][CH2:18][N:13]([CH2:14][CH2:15]2)[CH2:12]1)=[O:24]
Reactant: COc1ccccc1C(=O)O
Reactant: N[C@@H]1CN2CCC1CC2
Agent: C[n+]1ccccc1Cl
Agent: Cl
Agent: [I-]
Solvent: CC#N
Solvent: O
Solvent: CCN(CC)CC
Product: COc1ccccc1C(=O)N[C@@H]1CN2CCC1CC2
Reaction time: 8 h
Yield: 84.9 %

Procedure:
1.5 ml of Acetonitrile and Triethylamine (700 uL, 5.0 mmol) was added to a flask charged with (S)-(−)-3-Aminoquinuclidine dihydrochloride (199 mg, 1.0 mmol) and o-Methoxybenzoic acid (167 mg, 1.1 mmol), followed by addition of 2-Chloro-1-methyl pyridinium iodide (383 mg, 1.5 mmol) at room temperature. After stirring overnight, about 2 ml of water was added to reaction mixture to resolve a clear solution that was subsequently injected into a Preparative HPLC instrument for purification. Desired fractions were combined and concentrated under vacuum. (S)-2-methoxy-N-(quinuclidin-3-yl)benzamide (221 mg, 85% yield) was isolated as an oil. 1H NMR (400 MHz, Methanol-D4) δ (ppm): 7.79 (dd, J=7.7 1.6 Hz, 1H), 7.51 (td, J=8.0, 1.6 Hz, 1H), 7.15 (d, J=8.5 Hz, 1H), 7.06 (t, J=7.4 Hz, 1H), 4.45 (m, 4H), 3.97 (s, 3H), 3.82 (ddd, J=11.7, 9.9, 2.0 Hz 1H), 3.37 (m, 4H), 2.37 (q, J=3.2 Hz, 1H), 2.20 (m, 1H), 2.09 (m, 2H), 1.99 (m, 1H). LCMS (ESI): m/z 261.1 (M+H [C15H20N2O]=261.15).
Reaction SMILES: [CH3:1]C(C)([O-])C.[K+].[CH3:7][C@@:8]12[C:24](=O)[CH2:23][CH2:22][C@H:21]1[C@H:20]1[C@@H:11]([C:12]3[CH:13]=[CH:14][C:15]([OH:26])=[CH:16][C:17]=3[CH2:18][CH2:19]1)[CH2:10][CH2:9]2.O>[Br-].C[P+](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.C1COCC1>[CH3:7][C:8]12[CH2:9][CH2:10][CH:11]3[CH:20]([CH2:19][CH2:18][C:17]4[CH:16]=[C:15]([OH:26])[CH:14]=[CH:13][C:12]=43)[CH:21]1[CH2:22][CH2:23][C:24]2=[CH2:1]
Reactant: C[C@]12CC[C@@H]3c4ccc(O)cc4CC[C@H]3[C@@H]1CCC2=O
Reactant: CC(C)(C)[O-]
Agent: C[P+](c1ccccc1)(c1ccccc1)c1ccccc1
Agent: [Br-]
Agent: [K+]
Solvent: C1CCOC1
Solvent: O
Product: C=C1CCC2C3CCc4cc(O)ccc4C3CCC12C
Reaction time: 0.17 h
Yield: 10.7 %

Procedure:
Potassium tert-butoxide (220 mg, 1.96 mmol) was added to dry THF (5 ml) and stirred for 10 minutes to complete dissolution of the salt. Methyl triphenylphosphonium bromide (700 mg, 1.96 mmol) was added portionwise to the salt solution. Estrone (500 mg, 1.85 mmol) was dissolved in THF (5 ml) and added dropwise via a syringe to the bright yellow solution. After stirring at room temperature for 2 h, the reaction was heated at reflux overnight. The reaction was cooled, water added (10 ml) and the mixture extracted using ethyl acetate (3×10 ml). The combined organic fractions were combined, washed with water (2×10 ml) and brine (10 ml), dried (Na2SO4) and concentrated in vacuo. Flash column chromatography (SiO2 hexane:ethyl acetate 9:1) and recrystallisation from toluene/hexane afforded alkene 11 as a white crystalline solid (53 mg, 0.198 mmol, 11%). m.p. 130-132° C. (lit. m.p. 134-137° C.). δH (CDCl3) 0.82 (3H, s CH3), 1.20-1.62 (6H, m, alkyl H), 1.78-1.85 (1H, m, alkyl H), 1.90-1.99 (2H, m, alkyl H), 2.16-2.38 (3H, m, alkyl H), 2.50-2.59 (1H, m, alkyl H), 2.78-2.92 (2H, m, alkyl H), 4.50 (1H, s, OH), 4.67 (2H, t, J=2.0, olefinic H), 6.57 (1H, d, J=2.7, ArH-4), 6.63 (1H, dd, J=8.6, 2.7, ArH-2), 7.17 (1H, d, J=8.6, ArH-1).
Reaction SMILES: [I:1][C:2]1[CH:3]=[C:4]([CH:7]=[CH:8][CH:9]=1)[CH2:5][OH:6].N1C=CN=C1.[Si:15](Cl)([C:28]([CH3:31])([CH3:30])[CH3:29])([C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1)[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1>C(Cl)Cl.CCOCC>[C:28]([Si:15]([C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1)([C:16]1[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=1)[O:6][CH2:5][C:4]1[CH:7]=[CH:8][CH:9]=[C:2]([I:1])[CH:3]=1)([CH3:31])([CH3:29])[CH3:30]
Reactant: OCc1cccc(I)c1
Reactant: CC(C)(C)[Si](Cl)(c1ccccc1)c1ccccc1
Agent: c1c[nH]cn1
Solvent: CCOCC
Solvent: ClCCl
Product: CC(C)(C)[Si](OCc1cccc(I)c1)(c1ccccc1)c1ccccc1
Reaction time: 1 h
Yield: 99.6 %

Procedure:
To a solution of 3-iodo-benzyl alcohol (4.68 g, 20 mmol) in CH2Cl2 (40 mL) is added imidazole (1.49 g, 22 mmol) and t-butyldiphenylsilyl chloride (5.74 g, 22 mmol). The resulting mixture is stirred for 1 h diluted with ether washed with water and brine, dried over MgSO4 and concentrated to give the title compound as an oil (9.41 g). MS (EI) 472 (M)+.
Reaction SMILES: [C:1]([Si:5]([O:18][CH2:19][C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][C:21]=1[CH2:26][S:27]([C:30]1[CH:35]=[CH:34][C:33]([Cl:36])=[CH:32][CH:31]=1)(=[O:29])=[O:28])([C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1)[C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1)([CH3:4])([CH3:3])[CH3:2].[Si:37]([O:54][CH2:55][CH2:56][CH2:57][CH2:58][CH2:59]O)([C:50]([CH3:53])([CH3:52])[CH3:51])([C:44]1C=CC=CC=1)[C:38]1C=CC=CC=1.C(C=P(CCCC)(CCCC)CCCC)#N.C(OCC)(=O)C>C1(C)C=CC=CC=1>[C:50]([Si:37]([O:54][CH2:55][CH2:56][CH2:57][CH2:58][CH2:59][CH:26]([C:21]1[CH:22]=[CH:23][CH:24]=[CH:25][C:20]=1[CH2:19][O:18][Si:5]([C:1]([CH3:4])([CH3:2])[CH3:3])([C:6]1[CH:7]=[CH:8][CH:9]=[CH:10][CH:11]=1)[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1)[S:27]([C:30]1[CH:35]=[CH:34][C:33]([Cl:36])=[CH:32][CH:31]=1)(=[O:28])=[O:29])([CH3:38])[CH3:44])([CH3:52])([CH3:53])[CH3:51]
Reactant: CC(C)(C)[Si](OCCCCCO)(c1ccccc1)c1ccccc1
Reactant: CC(C)(C)[Si](OCc1ccccc1CS(=O)(=O)c1ccc(Cl)cc1)(c1ccccc1)c1ccccc1
Agent: CCCCP(=CC#N)(CCCC)CCCC
Solvent: CCOC(C)=O
Solvent: Cc1ccccc1
Product: CC(C)(C)[Si](C)(C)OCCCCCC(c1ccccc1CO[Si](c1ccccc1)(c1ccccc1)C(C)(C)C)S(=O)(=O)c1ccc(Cl)cc1
Yield: 67.9 %

Procedure:
The t-butyl [[2-[[(4-chlorophenyl)sulfonyl]methyl]benzyl]oxy]diphenylsilane (1.00 g, 1.87 mmol) obtained in Example 280 and 5-(t-butyldiphenylsilyloxy)-1-pentanol (0.68 ml, 2.8 mmol) were dissolved in toluene (7 ml), followed by the addition of cyanomethylenetri-n-butylphosphorane (650 mg, 2.69 mmol). Under an argon atmosphere, the resulting mixture was heated under reflux for 14 hours. After the reaction mixture was allowed to cool down, 5-(t-butyldiphenylsilyloxy)-1-pentanol (0.34 ml, 1.4 mmol) and cyanomethylenetri-n-butylphosphorane (300 mg, 1.24 mmol) were added. Under an argon atmosphere, the resulting mixture was heated under reflux for 10 hours. The reaction mixture was then allowed to cool down. The residue obtained by concentrating the mixture under reduced pressure was subjected to flash silica gel chromatography, and the fraction obtained from the hexane:ethyl acetate=15:1 eluate was concentrated under reduced pressure, whereby the title compound (932 mg, 1.27 mmol, 68%) was obtained as a pale yellowish brown oil.
Reaction SMILES: [NH:1]1[CH2:6][CH2:5][CH2:4][CH:3]([CH2:7][N:8]2[C:14](=[O:15])[CH2:13][C:12]3[CH:16]=[C:17]4[O:22][CH2:21][O:20][C:18]4=[CH:19][C:11]=3[CH2:10][CH2:9]2)[CH2:2]1.[CH3:23][C:24]1[CH:25]=[C:26]([CH:32]=[CH:33][CH:34]=1)[O:27][CH2:28][CH2:29][CH2:30][Cl:31]>>[ClH:31].[CH3:23][C:24]1[CH:25]=[C:26]([CH:32]=[CH:33][CH:34]=1)[O:27][CH2:28][CH2:29][CH2:30][N:1]1[CH2:6][CH2:5][CH2:4][CH:3]([CH2:7][N:8]2[C:14](=[O:15])[CH2:13][C:12]3[CH:16]=[C:17]4[O:22][CH2:21][O:20][C:18]4=[CH:19][C:11]=3[CH2:10][CH2:9]2)[CH2:2]1
Reactant: Cc1cccc(OCCCCl)c1
Reactant: O=C1Cc2cc3c(cc2CCN1CC1CCCNC1)OCO3
Product: Cc1cccc(OCCCN2CCCC(CN3CCc4cc5c(cc4CC3=O)OCO5)C2)c1
Product: Cl

Procedure:
Prepared from 3-[(piperidin-3-yl)-methyl]-7,8-methylenedioxy-1,3,4,5-tetrahydro-2H-3-benzazepin-2-one and 3-(3-methylphenoxy)-propylchloride analogously to Example 1.
Reaction SMILES: [NH2:1][CH:2]1[CH:7]([CH3:8])[CH2:6][N:5](CC2C=CC=CC=2)[CH2:4][C:3]1([CH3:18])[CH2:16][CH3:17]>CO.[H][H].[OH-].[OH-].[Pd+2]>[NH2:1][CH:2]1[CH:7]([CH3:8])[CH2:6][NH:5][CH2:4][C:3]1([CH3:18])[CH2:16][CH3:17]
Reactant: [H][H]
Reactant: CCC1(C)CN(Cc2ccccc2)CC(C)C1N
Agent: [Pd+2]
Agent: [OH-]
Solvent: CO
Product: CCC1(C)CNCC(C)C1N

Procedure:
A mixture of 20% Pd(OH)2 on carbon (0.4 g) and 4-amino-1-benzyl-3,5-dimethyl-3-ethylpiperidine (2.2 g, 8.9 mmol) in methanol (15 ml) was stirred in hydrogen atmosphere (1 atm.) at 60° C. for 10 hr. The catalyst was filtered off, washed with methanol and filtrate was concentrated to dryness to afford 4-amino-3,5-dimethyl-3-ethylpiperidine as a semi solid. Yield 1.1 g (79%), C9H20N2, m/z 157 (M+1).
Reaction SMILES: [CH3:1][C:2]1[CH:18]=[C:17]([N:19]([CH2:22][CH3:23])[CH2:20][CH3:21])[CH:16]=[CH:15][C:3]=1[C:4]([C:6]1[CH:14]=[CH:13][CH:12]=[CH:11][C:7]=1[C:8]([OH:10])=[O:9])=O.[CH3:24][N:25]([CH3:35])[C:26]1[CH:31]=[CH:30][CH:29]=[C:28]([N:32]([CH3:34])[CH3:33])[CH:27]=1.C(OC(=O)C)(=O)C.[OH-].[Na+]>Cl>[CH3:33][N:32]([CH3:34])[C:28]1[CH:27]=[C:26]([N:25]([CH3:35])[CH3:24])[CH:31]=[CH:30][C:29]=1[C:4]1([C:3]2[CH:15]=[CH:16][C:17]([N:19]([CH2:22][CH3:23])[CH2:20][CH3:21])=[CH:18][C:2]=2[CH3:1])[C:6]2[C:7](=[CH:11][CH:12]=[CH:13][CH:14]=2)[C:8](=[O:9])[O:10]1
Reactant: CN(C)c1cccc(N(C)C)c1
Reactant: CCN(CC)c1ccc(C(=O)c2ccccc2C(=O)O)c(C)c1
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: CC(=O)OC(C)=O
Product: CCN(CC)c1ccc(C2(c3ccc(N(C)C)cc3N(C)C)OC(=O)c3ccccc32)c(C)c1
Temperature: 95 °C

Procedure:
A mixture of 2-(2-methyl-4-(diethylamino)benzoyl)benzoic acid (25 g.), N,N,N',N'-tetramethyl-m-phenylenediamine (13.2 g.) and acetic anhydride (75 g.) was heated (to 95° C.) during one hour, then refluxed with dilute hydrochloric acid (32 g. concentrated hydrochloric acid plus 160 ml. water) during one and one-half hours. The resulting mixture was poured onto ice and the pH was adjusted to 6 with sodium hydroxide. Recrystallization of the resulting product afforded 3-(2,4-bis(dimethylamino)phenyl)-3-(2-methyl-4-(diethylamino)phenyl)phthalide (I: X=(CH3)2N, Y2 =CH3, Y4 =(CH3CH2)2N, Z4 =Z5 =Z6 =Z7 =H) in a first crop from toluene (m.p. 204°-206° C.) and in a second crop from a mixture of toluene and hexane (m.p. 191°-195° C.).
Reaction SMILES: [Cl:1][C:2]1[CH:8]=[CH:7][C:5]([NH2:6])=[CH:4][C:3]=1[N+:9]([O-:11])=[O:10].C(N(CC)CC)C.Cl[C:20]([O:22][CH2:23][C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1)=[O:21]>ClCCl.C(Cl)(Cl)Cl>[CH2:23]([O:22][C:20]([NH:6][C:5]1[CH:7]=[CH:8][C:2]([Cl:1])=[C:3]([N+:9]([O-:11])=[O:10])[CH:4]=1)=[O:21])[C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1
Reactant: O=C(Cl)OCc1ccccc1
Reactant: Nc1ccc(Cl)c([N+](=O)[O-])c1
Solvent: CCN(CC)CC
Solvent: ClCCl
Solvent: ClC(Cl)Cl
Product: O=C(Nc1ccc(Cl)c([N+](=O)[O-])c1)OCc1ccccc1
Yield: 90.5 %

Procedure:
Two equal batches of 4-chloro-3-nitroaniline (20.0 g each, 0.116 mol) were dissolved separately in freshly distilled dichloromethane (over P2O5) (150 mL each) and dry triethylamine (1.1 eq. each, 18 mL, 0.128 mol) under a drierite drying tube. Each of the reaction mixtures was chilled in an ice bath and benzyl chloroformate (50 mL each, 0.348 mol) was slowly added. The resulting solutions were heated to reflux for 4 days, and then they were combined and concentrated. The residue was further concentrated in vacuo using a kugelrohr apparatus (0.1 mm Hg, 60° C.) to give a thick oil. The oily material was dissolved in chloroform (300 mL) and washed with brine (100 mL). The organic layer was dried over sodium sulfate and concentrated in vacuo. The crude product was purified on a silica gel column, using a 2.5% methanol/chloroform as a solvent. A total yield of 32.2 g (46% yield) of N-benzyloxycarbonyl-4-chloro-3-nitroaniline was isolated as a yellow oil that solidified upon refrigeration. Rf320.61 (20% ethyl acetate/hexane). IR (neat) 3424, 3100, 3060, 3025, 2918, 2865, 1603, 1528, 1493, 1448, 1395, 1351, 1231, 1204, 1146, 1071, 1027, 960, 894, 841, 805, 734, 694. 1H-NMR (500 MHz, CDCl3) 7.28 (t, 9.0, 2H), 7.24 (s br, 1H), 7.22 (t, 9.0, 1H), 7.16 (d, 8.0, 1H), 7.13 (d, 9.0, 2H), 6.98 (d, 3.0, 1H), 6.73 (dd, 3.0, 8.0, 1H), 4.60 (s, 2H).