Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: C(N(CC)CC)C.[CH2:8]([O:12][C:13]1[CH:18]=[CH:17][C:16]([S:19](Cl)(=[O:21])=[O:20])=[CH:15][CH:14]=1)[C:9]#[C:10][CH3:11].[NH2:23][CH2:24][C:25]([N:34]1[CH2:39][CH2:38][N:37]([C:40]([O:42][C:43]([CH3:46])([CH3:45])[CH3:44])=[O:41])[CH2:36][CH2:35]1)([C:30]([O:32][CH3:33])=[O:31])[C:26]([O:28][CH3:29])=[O:27]>ClCCl>[C:43]([O:42][C:40]([N:37]1[CH2:38][CH2:39][N:34]([C:25]([CH2:24][NH:23][S:19]([C:16]2[CH:17]=[CH:18][C:13]([O:12][CH2:8][C:9]#[C:10][CH3:11])=[CH:14][CH:15]=2)(=[O:21])=[O:20])([C:30]([O:32][CH3:33])=[O:31])[C:26]([O:28][CH3:29])=[O:27])[CH2:35][CH2:36]1)=[O:41])([CH3:45])([CH3:46])[CH3:44]
Reactant: CC#CCOc1ccc(S(=O)(=O)Cl)cc1
Reactant: COC(=O)C(CN)(C(=O)OC)N1CCN(C(=O)OC(C)(C)C)CC1
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: CC#CCOc1ccc(S(=O)(=O)NCC(C(=O)OC)(C(=O)OC)N2CCN(C(=O)OC(C)(C)C)CC2)cc1
Temperature: 25 °C
Reaction time: 2 h
Yield: 54.2 %

Procedure:
1.1 ml (8 mmol) of triethylamine and then 1.8 ml (7 mmol) of 4-but-2-ynyloxybenzenesulfonyl chloride are added to a solution of 2.5 g (7 mmol) of dimethyl 2-aminomethyl-2-(4-tert-butoxycarbonylpiperazin-1-yl)malonate in 30 ml of dichloromethane. The reaction medium is stirred at ambient temperature for 2 hours and then concentrated under vacuum. The crude product obtained is purified by chromatography on silica gel, elution being carried out with a 70/30 heptane/ethyl acetate mixture. 2.1 g (51%) of dimethyl 2-(4-tert-butoxycarbonylpiperazin-1-yl)-2-[(4-but-2-ynyloxybenzenesulfonylamino)methyl]malonate are obtained in the form of a white solid.
Reaction SMILES: C(OC([N:8]1[C:17]2[C:12](=[CH:13][CH:14]=[C:15]([O:18][CH3:19])[CH:16]=2)[CH2:11][CH2:10][CH2:9]1)=O)(C)(C)C.FC(F)(F)C(O)=O.C(=O)([O-])[O-].[Na+].[Na+]>ClCCl>[CH3:19][O:18][C:15]1[CH:16]=[C:17]2[C:12]([CH2:11][CH2:10][CH2:9][NH:8]2)=[CH:13][CH:14]=1
Reactant: COc1ccc2c(c1)N(C(=O)OC(C)(C)C)CCC2
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: ClCCl
Solvent: O=C(O)C(F)(F)F
Product: COc1ccc2c(c1)NCCC2
Temperature: 25 °C
Reaction time: 24 h
Yield: 113.3 %

Procedure:
To a solution of 7-methoxy-3,4-dihydro-2H-quinoline-1-carboxylic acid tert-butyl ester (52 mg, 0.20 mmol) in dichloromethane (7 ml) at 0° C. was added dropwise trifluoroacetic acid (0.23 ml, 3.01 mmol) and the reaction mixture was then stirred at room temperature for 24 h. The mixture was then made basic to pH 9 by dropwise addition of saturated aq. sodium carbonate solution. The mixture was extracted three times with a 1:1 mixture of ethyl acetate and tetrahydrofuran, the phases separated, and the organic phase dried over sodium sulphate and concentrated in vacuo to yield the title compound as a light brown oil (37 mg, 92%); MS (ISP): 164.4 ([M+H]+).
Reaction SMILES: [N+:1]([C:4]1[CH:5]=[C:6]2[C:11](=[O:12])[O:10][C:8](=O)[C:7]2=[CH:13][CH:14]=1)([O-:3])=[O:2].Cl.[NH2:16][CH:17]1[CH2:23][CH2:22][C:21](=[O:24])[NH:20][C:18]1=[O:19].C([O-])(=O)C.[Na+]>C(O)(=O)C>[O:10]=[C:8]1[C:7]2[C:6](=[CH:5][C:4]([N+:1]([O-:3])=[O:2])=[CH:14][CH:13]=2)[C:11](=[O:12])[N:16]1[CH:17]1[CH2:23][CH2:22][C:21](=[O:24])[NH:20][C:18]1=[O:19]
Reactant: NC1CCC(=O)NC1=O
Reactant: O=C1OC(=O)c2cc([N+](=O)[O-])ccc21
Agent: CC(=O)[O-]
Agent: Cl
Agent: [Na+]
Solvent: CC(=O)O
Product: O=C1CCC(N2C(=O)c3ccc([N+](=O)[O-])cc3C2=O)C(=O)N1
Yield: 54.3 %

Procedure:
A mixture of 4-nitrophthalic anhydride (1.7 g, 8.5 mmol), α-aminoglutarimide hydrochloride (1.4 g, 8.5 mmol) and sodium acetate (0.7 g, 8.6 mmol) in glacial acetic acid (30 mL) was heated under reflux for 17 hours. The mixture was concentrated in vacuo and the residue was stirred with methylene chloride (40 mL) and water (30 mL). The aqueous layer was separated, extracted with methylene chloride (2×40 mL). The combined methylene chloride solutions were dried over magnesium sulfate and concentrated in vacuo to give 1.4 g (54%) of 1,3-dioxo-2-(2,6-dioxopiperidin-3-yl)-5-nitroisoindoline as a light brown solid. An analytical sample was obtained by recrystallization from methanol: mp 228.5-229.5° C.; 1H NMR (DMSO-d6) δ 11.18 (s, 1 H), 8.69-8.65 (d, d J=1.9 and 8.0 Hz, 1H), 8.56 (d, J=1.9 Hz, 1H), 8.21 (d, H=8.2 Hz, 1H), 5.28 (d, d J=5.3 and 12.8 Hz, 1H), 2.93-2.07 (m, 4H); 13C NMR (DMSO-d6) δ 172.66, 169.47, 165.50, 165.23, 151.69, 135.70, 132.50, 130.05, 124.97, 118.34, 49.46, 30.85, 21.79; Anal. Calcd for C13H9N3O6: C, 51.49; H, 2.99; N, 13.86. Found: C, 51.59; H, 3.07; N, 13.73.
Reaction SMILES: [N+:1]([C:4]1[CH:11]=[CH:10][CH:9]=[CH:8][C:5]=1[CH:6]=O)([O-:3])=[O:2].[CH2:12]([O:14][CH:15]([O:24][CH2:25][CH3:26])[C:16](=[O:23])[CH2:17][C:18]([O:20][CH2:21][CH3:22])=[O:19])[CH3:13].N1CCCCC1.O>C1C=CC=CC=1>[N+:1]([C:4]1[CH:11]=[CH:10][CH:9]=[CH:8][C:5]=1[CH:6]=[C:17]([C:16]([CH:15]([O:14][CH2:12][CH3:13])[O:24][CH2:25][CH3:26])=[O:23])[C:18]([O:20][CH2:21][CH3:22])=[O:19])([O-:3])=[O:2]
Reactant: O=Cc1ccccc1[N+](=O)[O-]
Reactant: CCOC(=O)CC(=O)C(OCC)OCC
Solvent: C1CCNCC1
Solvent: c1ccccc1
Solvent: O
Product: CCOC(=O)C(=Cc1ccccc1[N+](=O)[O-])C(=O)C(OCC)OCC

Procedure:
(4)-(1) A solution of 2-nitrobenzaldehyde (9.0672 g), ethyl 4,4-diethoxyacetoacetate (13.0944 g) and piperidine (1ml) in benzene (45 ml) was refluxed under azeotropic dehydration for 3 hours. To the resultant solution was added water, and the solution was extracted with diethyl ether. The extract was washed three times with water, dried and then the solvent was removed under reduced pressure to give ethyl 2-(2-nitrobenzylidene)-4,4-diethoxyacetoacetate. The mixture of the compound obtained above and ethyl 3-aminocrotonate (7.7496 g) was heated in an oil bath (95° to 100° C.) for 8 hours. The resultant mixture was extracted with diethyl ether, and the extract was washed with water and dried. The solvent was removed from the extract. The residue was purified by column chromatography on silica gel with an eluent (benzene:ethyl acetate=20:1) to give oily diethyl 2-methyl-4-(2-nitrophenyl)-6-diethoxymethyl-1,4-dihydropyridine-3,5-dicarboxylate (19.3 g). The product was crystallized in n-hexane and the crystals were collected by filtration and then recrystallized from a mixture of n-hexane and diethyl ether to give the pure compound, m.p. 80° to 81.5° C.
Reaction SMILES: [Cl:1][C:2]1[CH:20]=[CH:19][C:5]([O:6][C:7]2[CH:18]=[CH:17][C:10]([O:11][CH:12]([CH3:16])[C:13](Cl)=[O:14])=[CH:9][CH:8]=2)=[CH:4][CH:3]=1.[N+:21]([C:24]1[CH:37]=[CH:36][C:27]([O:28][C:29]2[CH:34]=[CH:33][C:32]([OH:35])=[CH:31][CH:30]=2)=[CH:26][CH:25]=1)([O-:23])=[O:22].C(N(CC)CC)C>O1CCCC1>[Cl:1][C:2]1[CH:20]=[CH:19][C:5]([O:6][C:7]2[CH:18]=[CH:17][C:10]([O:11][CH:12]([CH3:16])[C:13]([O:35][C:32]3[CH:31]=[CH:30][C:29]([O:28][C:27]4[CH:36]=[CH:37][C:24]([N+:21]([O-:23])=[O:22])=[CH:25][CH:26]=4)=[CH:34][CH:33]=3)=[O:14])=[CH:9][CH:8]=2)=[CH:4][CH:3]=1
Reactant: CC(Oc1ccc(Oc2ccc(Cl)cc2)cc1)C(=O)Cl
Reactant: O=[N+]([O-])c1ccc(Oc2ccc(O)cc2)cc1
Solvent: CCN(CC)CC
Solvent: C1CCOC1
Product: CC(Oc1ccc(Oc2ccc(Cl)cc2)cc1)C(=O)Oc1ccc(Oc2ccc([N+](=O)[O-])cc2)cc1
Yield: 82 %

Procedure:
2-(4-(4-Chlorophenoxy)phenoxy)propionic acid chloride (0.6 g) and 4-(4-nitrophenoxy)phenol (0.5 g) were dissolved in dry tetrahydrofuran (10 ml), and the solution was stirred with an addition of triethylamine (0.3 ml) at room temperature for 2 hours. After completion of the reaction, the solvent was evaporated under a reduced pressure, the residue was dissolved in methylene chloride (20 ml), and washed with 1 N hydrochloric acid, water, saturated aqueous sodium hydrogen carbonate, water, saturated aqueous sodium hydrogen carbonate, water, and aqueous saturated sodium chloride. After drying over anhydrous magnesium sulfate, the solvent was evaporated and the residue obtained was purified by medium pressure column chromatography to obtain 4-(4-nitrophenoxy)phenyl 2-(4-(4-chlorophenoxy)phenoxy)propionate (0.8 g)
Reaction SMILES: [OH:1][C:2]12[CH2:11][C:6]3([OH:12])[CH2:7][CH:8]([CH2:10][C:4]([OH:13])([CH2:5]3)[CH2:3]1)[CH2:9]2.CN(C)C.[CH3:18][Si:19](Cl)([CH3:21])[CH3:20]>C(Cl)Cl>[OH:1][C:2]12[CH2:11][C:6]3([O:12][Si:19]([CH3:21])([CH3:20])[CH3:18])[CH2:7][CH:8]([CH2:10][C:4]([OH:13])([CH2:5]3)[CH2:3]1)[CH2:9]2
Reactant: C[Si](C)(C)Cl
Reactant: OC12CC3CC(O)(C1)CC(O)(C3)C2
Agent: CN(C)C
Solvent: ClCCl
Product: C[Si](C)(C)OC12CC3CC(O)(CC(O)(C3)C1)C2

Procedure:
This 1,3,5-trihydroxyadamantane was dissolved in methylene chloride. To this solution were added a small amount of trimethylamine, and then an equimolar amount of trimethylsilyl chloride. Reaction was carried out at room temperature. The reaction product was partitioned by high performance liquid chromatography to obtain 1,3-dihydroxy-5-trimethylsiloxyadamantane.
Reaction SMILES: [C:1]([O:5][C:6](=[O:19])[NH:7][C@@H:8]([C@@H:16]1[CH2:18][O:17]1)[CH2:9][C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1)([CH3:4])([CH3:3])[CH3:2].[NH:20]1[CH2:25][CH2:24][CH2:23][CH2:22][CH2:21]1>>[C:1]([O:5][C:6](=[O:19])[NH:7][C@H:8]([CH2:9][C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1)[C@@H:16]([OH:17])[CH2:18][N:20]1[CH2:25][CH2:24][CH2:23][CH2:22][CH2:21]1)([CH3:4])([CH3:3])[CH3:2]
Reactant: CC(C)(C)OC(=O)N[C@H](Cc1ccccc1)[C@@H]1CO1
Reactant: C1CCNCC1
Product: CC(C)(C)OC(=O)N[C@H](Cc1ccccc1)[C@@H](O)CN1CCCCC1

Procedure:
Using general procedure 1 with [(1R)-1-{(2R)-oxiran-2-yl}-2-phenyl-ethyl]carbamic acid tert-butylester (0.115 g, 0.44 mmol) and piperidine (0.218 mL, 2.20 mmol) give the title compound.
Reaction SMILES: N1C=CC=CC=1.[Br:7][C:8]1[CH:13]=[C:12]([NH:14][C:15](=[O:20])[C:16]([F:19])([F:18])[F:17])[CH:11]=[CH:10][C:9]=1[S:21](Cl)(=[O:23])=[O:22].[NH2:25][C:26]1[CH:27]=[CH:28][C:29]2[CH2:33][O:32][B:31]([OH:34])[C:30]=2[CH:35]=1>C(#N)C>[Br:7][C:8]1[CH:13]=[C:12]([NH:14][C:15](=[O:20])[C:16]([F:19])([F:18])[F:17])[CH:11]=[CH:10][C:9]=1[S:21](=[O:23])(=[O:22])[NH:25][C:26]1[CH:27]=[CH:28][C:29]2[CH2:33][O:32][B:31]([OH:34])[C:30]=2[CH:35]=1
Reactant: Nc1ccc2c(c1)B(O)OC2
Reactant: O=C(Nc1ccc(S(=O)(=O)Cl)c(Br)c1)C(F)(F)F
Solvent: CC#N
Solvent: c1ccncc1
Product: O=C(Nc1ccc(S(=O)(=O)Nc2ccc3c(c2)B(O)OC3)c(Br)c1)C(F)(F)F
Reaction time: 8 h

Procedure:
Pyridine (1.5 equiv) was added dropwise to the cooled suspension of the crude 2-bromo-4-(2,2,2-trifluoroacetamido)benzene-1-sulfonyl chloride (24 g, 0.06 mol) and 6-aminobenzo[c][1,2]oxaborol-1(3H)-ol (1.2 eq) in acetonitrile (300 ml) at 0° C. over 10 min. The r×n mix was stirred overnight. The solid was filtered and washed with EtOAc. The filtrate was washed with, H2O, brine, dried over MgSO4, filtered, and concentrated to dryness to give crude N-(3-bromo-4-(N-(1-hydroxy-1,3-dihydrobenzo[c][1,2]oxaborol-6-yl)sulfamoyl)phenyl)-2,2,2-trifluoroacetamide which was purified by flash chromatography on silica gel. 1H NMR (400 MHz, DMSO-d6) δ (ppm): 11.6 (s, 1H), 10.56 (s, 1H), 9.20 (s, 1H), 8.12 (d, J=1.9 Hz, 1H), 8.06 (d, J=8.8 Hz, 1H), 7.79 (dd, J=2.0, 8.6 Hz, 1H), 7.47 (d, J=1.8 Hz, 1H), 7.24 (d, J=8.4 Hz, 1H), 7.20 (dd, J=1.9, 8.3 Hz, 1H), 4.85 (s, 2H). MS (ESI) m/z=479 (M+1).
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([C:8]2[C:17]3[C:12](=[CH:13][CH:14]=[C:15]([C:18]([C:25]4[N:29]([CH3:30])[CH:28]=[N:27][CH:26]=4)([C:20]4[S:21][CH:22]=[CH:23][N:24]=4)[OH:19])[CH:16]=3)[N:11]=[C:10]([O:31]C)[CH:9]=2)[CH:5]=[CH:6][CH:7]=1.[NH4+].[OH-]>Cl.C1COCC1>[Cl:1][C:2]1[CH:3]=[C:4]([C:8]2[C:17]3[C:12](=[CH:13][CH:14]=[C:15]([C:18]([OH:19])([C:25]4[N:29]([CH3:30])[CH:28]=[N:27][CH:26]=4)[C:20]4[S:21][CH:22]=[CH:23][N:24]=4)[CH:16]=3)[NH:11][C:10](=[O:31])[CH:9]=2)[CH:5]=[CH:6][CH:7]=1
Reactant: COc1cc(-c2cccc(Cl)c2)c2cc(C(O)(c3nccs3)c3cncn3C)ccc2n1
Agent: Cl
Agent: [NH4+]
Agent: [OH-]
Solvent: C1CCOC1
Product: Cn1cncc1C(O)(c1ccc2[nH]c(=O)cc(-c3cccc(Cl)c3)c2c1)c1nccs1
Yield: 102.8 %

Procedure:
A mixture of intermediate (10)(0.0065 mol) in HCl 3N (100 ml) and THF (100 ml) was stirred and refluxed for 6 hours. The mixture was poured out on ice, alkalized with a concentrated NH4OH solution and extracted with DCM. The organic layer was separated, dried (MgSO4), filtered and the solvent was evaporated till dryness, yielding 3 g (>100%) of 4-(3-chlorophenyl)-6-[hydroxy(1-methyl-1H-imidazol-5-yl)-2-thiazolylmethyl]-2(1H)-quinolinone (intermediate 11).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:26]=[C:27]([O:31][CH3:32])[C:28]=1[O:29][CH3:30])[C:6]([N:8]1[CH2:12][CH2:11][C:10]([C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)([CH2:13][CH2:14]OS(C)(=O)=O)[CH2:9]1)=[O:7].Cl.[OH:34][CH2:35][CH2:36][N:37]1[C:41]2[CH:42]=[CH:43][CH:44]=[CH:45][C:40]=2[N:39]=[C:38]1[N:46]1[CH2:52][CH2:51][CH2:50][NH:49][CH2:48][CH2:47]1.[I-].[K+].C(N(CC)C(C)C)(C)C>C(#N)C.CO.C(OCC)(=O)C.C(OCC)(=O)C>[CH3:32][O:31][C:27]1[CH:26]=[C:5]([CH:4]=[C:3]([O:2][CH3:1])[C:28]=1[O:29][CH3:30])[C:6]([N:8]1[CH2:12][CH2:11][C:10]([CH2:13][CH2:14][N:49]2[CH2:50][CH2:51][CH2:52][N:46]([C:38]3[N:37]([CH2:36][CH2:35][OH:34])[C:41]4[CH:42]=[CH:43][CH:44]=[CH:45][C:40]=4[N:39]=3)[CH2:47][CH2:48]2)([C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)[CH2:9]1)=[O:7]
Reactant: OCCn1c(N2CCCNCC2)nc2ccccc21
Reactant: COc1cc(C(=O)N2CCC(CCOS(C)(=O)=O)(c3ccccc3)C2)cc(OC)c1OC
Agent: Cl
Agent: [I-]
Agent: [K+]
Solvent: CO
Solvent: CCOC(C)=O
Solvent: CCN(C(C)C)C(C)C
Product: COc1cc(C(=O)N2CCC(CCN3CCCN(c4nc5ccccc5n4CCO)CC3)(c3ccccc3)C2)cc(OC)c1OC
Reaction time: 18 h

Procedure:
Combine 1-(3,4,5-trimethoxybenzoyl)-3-phenyl-3-(2-methanesulfonyloxyethyl)pyrrolidine (prepared from (−)-3-phenyl-3-(2-hydroxyethyl)pyrrolidine(R,R)-di-p-anisoyltartaric acid salt) (0.3 g, 1.2 mmol), 4-(1-(2-hydroxyethyl)-1H-benzimidazol-2-yl)[1,4]diazepane hydrochloric acid salt (0.52 g, 1.12 mmol), potassium iodide (0.2 g), and N,N-diisopropylethylamine (0.4 g, 4 mmol) in acetonitrile (20 mL). Heat to reflux. After 18 hours, cool and dilute the reaction mixture ethyl acetate. Extract three times with a half saturated aqueous sodium bicarbonate solution, and then brine. Dry the organic layer over Na2SO4, filter, and concentrate in uacuo to obtain a residue. Chromatograph the residue on silica gel eluting with 40% methanol/ethyl acetate/1% concentrated aqueous ammonia solution to give, after drying in vacuo at 70° C., the title compound: mp; 73-78° C. [α]2D0=+7.7° (c=1.04, methanol). Rf=0.23 (silica gel, 40% methanol/ethyl acetate).
Reaction SMILES: Br[C:2]1[CH:11]=[C:10]2[C:5]([CH:6]=[C:7]([Cl:12])[CH:8]=[N:9]2)=[CH:4][CH:3]=1.[C:13]([Cu])#[N:14].CN(C=O)C>C(Cl)Cl>[Cl:12][C:7]1[CH:8]=[N:9][C:10]2[C:5]([CH:6]=1)=[CH:4][CH:3]=[C:2]([C:13]#[N:14])[CH:11]=2
Reactant: Clc1cnc2cc(Br)ccc2c1
Reactant: N#C[Cu]
Solvent: CN(C)C=O
Solvent: ClCCl
Product: N#Cc1ccc2cc(Cl)cnc2c1
Temperature: 150 °C

Procedure:
To a flask containing a stir bar was added 7-Bromo-3-chloroquinoline (1.0 g, 4.1 mmol), CuCN (0.55 g, 6.2 mmol), and DMF (25 mL). The mixture was then refluxed at 150° C. overnight. When the reaction was complete, as evidenced by LC analysis, the reaction flask was taken out of the oil bath and cooled to room temperature. To the reaction mixture was then poured DCM (20 mL) and a precipitate formed immediately, which was filtered off. The crude product was adsorbed onto silica gel and purified by silica gel column chromatography (Hexanes:DCM→1:1) to provide the title product.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[N:4][CH:5]=[C:6]([Cl:20])[C:7]=1[S:8][C:9]1[S:13][C:12]([C:14](Cl)=[O:15])=[CH:11][C:10]=1[N+:17]([O-:19])=[O:18].[CH:21]1([NH2:27])[CH2:26][CH2:25][CH2:24][CH2:23][CH2:22]1>>[CH:21]1([NH:27][C:14]([C:12]2[S:13][C:9]([S:8][C:7]3[C:2]([Cl:1])=[CH:3][N:4]=[CH:5][C:6]=3[Cl:20])=[C:10]([N+:17]([O-:19])=[O:18])[CH:11]=2)=[O:15])[CH2:26][CH2:25][CH2:24][CH2:23][CH2:22]1
Reactant: O=C(Cl)c1cc([N+](=O)[O-])c(Sc2c(Cl)cncc2Cl)s1
Reactant: NC1CCCCC1
Product: O=C(NC1CCCCC1)c1cc([N+](=O)[O-])c(Sc2c(Cl)cncc2Cl)s1

Procedure:
Prepared according to the procedure described for example 50 from 5-[(3,5-dichloro-4-pyridyl)sulfanyl]-4-nitro-thiophene-2-carbonyl chloride (120 mg, 0.33 mmol) and cyclohexylamine (49 mg, 0.39 mmol). The title compound was obtained as a solid (60 mg, 34% yield). 1H NMR (400 MHz, d6-DMSO) δ: 8.98 (2H, s), 8.62 (1H, m), 8.50 (1H, s), 3.63 (1H, m), 1.71 (4H, m), 1.59 (1H, m), 1.24 (4H, m), 1.09 (1H, m). MS m/z: 430.13, 432.07 [M+H]+.
Reaction SMILES: [CH:1]([NH:3][CH2:4][CH:5]1[C:11]2[CH:12]=[CH:13][CH:14]=[CH:15][C:10]=2[CH2:9][C:8]2[CH:16]=[CH:17][CH:18]=[CH:19][C:7]=2[CH2:6]1)=O.[OH-].[Na+].C(Cl)(Cl)Cl>O.C1C=CC=CC=1>[CH2:4]1[CH:5]2[CH2:6][C:7]3[CH:19]=[CH:18][CH:17]=[CH:16][C:8]=3[CH2:9][C:10]3[C:11]2=[C:12]([CH:13]=[CH:14][CH:15]=3)[CH:1]=[N:3]1
Reactant: O=CNCC1Cc2ccccc2Cc2ccccc21
Agent: [Na+]
Agent: [OH-]
Solvent: ClC(Cl)Cl
Solvent: O
Solvent: c1ccccc1
Product: C1=NCC2Cc3ccccc3Cc3cccc1c32
Temperature: 0 °C
Reaction time: 3.5 h

Procedure:
N-Formyl-10,11-dihydro-5H-dibenzo[a,d]cycloheptene-10-methylamine (6.7 g, 0.027 mole), described in Example 334, in combined with polyphosphoric acid (50 g) and the mixture stirred for 3.5 hr. at 155° - 160° C. (bath temperature). The darkish reaction mixture is poured hot into stirred ice-water (400 ml). After stirring for 0.5 hr. (and treatment of the sticky precipitate with a glass rod) a solution of sodium hydroxide (60 g) in water is added, followed by chloroform. The chloroform solution is twice replaced by fresh chloroform and after 1 hr. the precipitate is almost dissolved. The combined chloroform solutions are washed with water, dried (Na2SO4) and taken to dryness to give a dark residue. The residue is dissolved in a little benzene and subjected to chromatography on neutral alumina (300 g). Elution with hexane-benzene (1:1) and benzene-ethyl acetate (9.5: 0.5) gives an oil which on crystallization from a concentrated ether solution gives 1,7,12,12a-tetrahydrobenzo[1,2]cyclohepta[4,5,6-de]isoquinoline, m.p. 91° - 93° C, γmaxCHCl3 1629, 1588, 1578, 1490 cm-1. The corresponding hydrochloride acid addition salt has m.p. 285° - 289° C, after recrystallization from chloroform-ether and methanol-ether.
Reaction SMILES: [Si]([O:18][CH:19]1[CH2:22][N:21]([C:23]2[S:24][CH:25]=[C:26]([C:28]([N:30]3[CH2:33][CH:32]([O:34][CH3:35])[CH2:31]3)=[O:29])[N:27]=2)[CH2:20]1)(C(C)(C)C)(C1C=CC=CC=1)C1C=CC=CC=1.[F-].C([N+](CCCC)(CCCC)CCCC)CCC>O1CCCC1>[OH:18][CH:19]1[CH2:22][N:21]([C:23]2[S:24][CH:25]=[C:26]([C:28]([N:30]3[CH2:33][CH:32]([O:34][CH3:35])[CH2:31]3)=[O:29])[N:27]=2)[CH2:20]1
Reactant: COC1CN(C(=O)c2csc(N3CC(O[Si](c4ccccc4)(c4ccccc4)C(C)(C)C)C3)n2)C1
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: [F-]
Solvent: C1CCOC1
Product: COC1CN(C(=O)c2csc(N3CC(O)C3)n2)C1
Reaction time: 0.5 h
Yield: 104.4 %

Procedure:
To a solution of 3-t-butyldiphenylsilyloxy-1-[4-(3-methoxyazetidine-1-carbonyl)-1,3-thiazol-2-yl]azetidine (870 mg, 1.71 mmol) (obtained as described in Reference Example 31(2)) in anhydrous tetrahydrofuran (45 ml) was added a solution of 1.0M tetra-n-butylammonium fluoride in tetrahydrofuran (2.06 ml, 2.06 mmol) in an ice bath, and then the mixture was stirred for 30 minutes. After checking the completion of the reaction, the reaction mixture was concentrated under reduced pressure. The residue was purified by chromatography on a silica gel column using ethyl acetate:methanol (9:1) as the eluant to afford 3-hydroxy-1-[4-(3-methoxyazetidine-1-carbonyl)-1,3-thiazol-2-yl]azetidine (481 mg, yield 100%) as a white solid.
Reaction SMILES: [CH2:1]([Mg]Cl)[CH2:2][CH2:3][CH3:4].Cl[SiH:8]1[CH2:13][CH2:12][CH:11]([CH2:14][CH2:15][CH2:16][CH2:17][C@H:18]2[CH2:23][CH2:22][C@H:21]([C:24]3[CH:29]=[CH:28][C:27]([O:30][CH:31]([F:33])[F:32])=[CH:26][CH:25]=3)[CH2:20][CH2:19]2)[CH2:10][CH2:9]1>C1COCC1>[F:32][CH:31]([F:33])[O:30][C:27]1[CH:28]=[CH:29][C:24]([C@H:21]2[CH2:22][CH2:23][C@H:18]([CH2:17][CH2:16][CH2:15][CH2:14][C@H:11]3[CH2:12][CH2:13][Si@H:8]([CH2:1][CH2:2][CH2:3][CH3:4])[CH2:9][CH2:10]3)[CH2:19][CH2:20]2)=[CH:25][CH:26]=1
Reactant: FC(F)Oc1ccc([C@H]2CC[C@H](CCCCC3CC[SiH](Cl)CC3)CC2)cc1
Reactant: CCCC[Mg]Cl
Solvent: C1CCOC1
Product: CCCC[Si@H]1CC[C@H](CCCC[C@H]2CC[C@H](c3ccc(OC(F)F)cc3)CC2)CC1

Procedure:
50 ml (0.13 moles) of a THF solution of 2.5M of n-butylmagnesium chloride was dropped in a mixed solution of 41.5 g (0.1 mol) of 1-chloro-4-(4-(trans-4-(4-difluoromethoxyphenyl)cyclohexyl)butyl)-1-silacyclohexane and 30 ml of THF. The resultant product was found to be a mixture of trans and cis isomers with respect to the silacyclohexane ring. The product was subjected to ordinary aftertreatments, followed by isolation through chromatography to obtain 43.7 g (yield: 90%) of the intended trans isomer product.
Reaction SMILES: [CH2:1]([C:8]1[N:12]([CH2:13][C:14]2[CH:19]=[CH:18][C:17]([C:20]3[C:21]([C:26]([O:28]C(C)(C)C)=[O:27])=[CH:22][CH:23]=[CH:24][CH:25]=3)=[CH:16][CH:15]=2)[C:11]2[CH:33]=[C:34]([CH3:38])[C:35]([CH3:37])=[CH:36][C:10]=2[N:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.FC(F)(F)C(O)=O>C(Cl)Cl>[CH2:1]([C:8]1[N:12]([CH2:13][C:14]2[CH:15]=[CH:16][C:17]([C:20]3[C:21]([C:26]([OH:28])=[O:27])=[CH:22][CH:23]=[CH:24][CH:25]=3)=[CH:18][CH:19]=2)[C:11]2[CH:33]=[C:34]([CH3:38])[C:35]([CH3:37])=[CH:36][C:10]=2[N:9]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: Cc1cc2nc(Cc3ccccc3)n(Cc3ccc(-c4ccccc4C(=O)OC(C)(C)C)cc3)c2cc1C
Solvent: ClCCl
Solvent: O=C(O)C(F)(F)F
Product: Cc1cc2nc(Cc3ccccc3)n(Cc3ccc(-c4ccccc4C(=O)O)cc3)c2cc1C

Procedure:
Prepared in analogous manner to Example 9 from tert.butyl 4'-[(2-benzyl-5,6-dimethyl-benzimidazol-1-yl)-methyl]biphenyl-2-carboxylate and trifluoroacetic acid in methylene chloride.
Reaction SMILES: [CH3:1][C:2]1[CH:10]=[C:6]([C:7]([OH:9])=O)[C:5]([OH:11])=[CH:4][CH:3]=1.[CH3:12][C:13]1[CH:19]=[CH:18][C:17]([C:20]([F:23])([F:22])[F:21])=[CH:16][C:14]=1[NH2:15]>>[OH:11][C:5]1[CH:4]=[CH:3][C:2]([CH3:1])=[CH:10][C:6]=1[C:7]([NH:15][C:14]1[CH:16]=[C:17]([C:20]([F:21])([F:22])[F:23])[CH:18]=[CH:19][C:13]=1[CH3:12])=[O:9]
Reactant: Cc1ccc(O)c(C(=O)O)c1
Reactant: Cc1ccc(C(F)(F)F)cc1N
Product: Cc1ccc(O)c(C(=O)Nc2cc(C(F)(F)F)ccc2C)c1
Yield: 14.2 %

Procedure:
Using 5-methylsalicylic acid and 2-methyl-5-(trifluoromethyl)aniline as the raw materials, the same operation as the example 16 gave the title compound.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][N:5]=[C:4]2[NH:8][CH:9]=[CH:10][C:3]=12.[H-].[Na+].Cl[CH2:14][O:15][CH2:16][CH2:17][Si:18]([CH3:21])([CH3:20])[CH3:19]>CN(C=O)C.CCOC(C)=O>[Cl:1][C:2]1[CH:7]=[CH:6][N:5]=[C:4]2[N:8]([CH2:14][O:15][CH2:16][CH2:17][Si:18]([CH3:21])([CH3:20])[CH3:19])[CH:9]=[CH:10][C:3]=12
Reactant: Clc1ccnc2[nH]ccc12
Reactant: C[Si](C)(C)CCOCCl
Agent: [H-]
Agent: [Na+]
Solvent: CCOC(C)=O
Solvent: CN(C)C=O
Product: C[Si](C)(C)CCOCn1ccc2c(Cl)ccnc21
Temperature: 25 °C
Reaction time: 0.25 h
Yield: 99 %

Procedure:
To a solution of 4-chloro-1H-pyrrolo[2,3-b]pyridine (3.05 g, 20 mmol, prepared according to Thibault, C. et al. Org. Lett. 2003, 5, 5023) in DMF (50 mL) at −40° C. under N2, was added NaH (60% in mineral oil, 880 mg, 22 mmol). The mixture was stirred at rt for 15 min, then cooled to −40° C. To this solution was added (2-(chloromethoxy)ethyl)trimethylsilane (3.67 g, 22 mmol). The resulting mixture was stirred at rt overnight. The mixture was diluted with EtOAc, washed twice with 10% LiCl, and dried over MgSO4. The title compound was purified by flash column chromatography (silica gel, eluding with hexane, followed by Et2O) to give the desired product (5.6 g, quantitiatve yield) as an oil. LC/MS(ESI+) m/z 283 (M+H)+.