Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: Cl[CH2:2][CH2:3][CH2:4][S:5](Cl)(=[O:7])=[O:6].Cl.Cl.[CH2:11]([O:18][C:19]1[CH:20]=[CH:21][C:22]2[C:23]3[N:31]([CH2:32][CH2:33][CH2:34][CH2:35][NH2:36])[C:30]([CH2:37][O:38][CH2:39][CH3:40])=[N:29][C:24]=3[CH:25]=[N:26][C:27]=2[CH:28]=1)[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1.C(N(CC)CC)C.[N:48]12[CH2:58][CH2:57][CH2:56][N:55]=[C:54]1[CH2:53][CH2:52][CH2:51][CH2:50][CH2:49]2>ClCCl>[CH2:11]([O:18][C:19]1[CH:20]=[CH:21][C:22]2[C:23]3[N:31]([CH2:32][CH2:33][CH2:34][CH2:35][N:36]4[CH2:2][CH2:3][CH2:4][S:5]4(=[O:7])=[O:6])[C:30]([CH2:37][O:38][CH2:39][CH3:40])=[N:29][C:24]=3[CH:25]=[N:26][C:27]=2[CH:28]=1)[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1.[N:48]12[CH2:58][CH2:57][CH2:56][N:55]=[C:54]1[CH2:53][CH2:52][CH2:51][CH2:50][CH2:49]2
Reactant: CCOCc1nc2cnc3cc(OCc4ccccc4)ccc3c2n1CCCCN
Reactant: O=S(=O)(Cl)CCCCl
Agent: Cl
Solvent: ClCCl
Solvent: C1CCC2=NCCCN2CC1
Solvent: CCN(CC)CC
Product: CCOCc1nc2cnc3cc(OCc4ccccc4)ccc3c2n1CCCCN1CCCS1(=O)=O
Reaction time: 17 h

Procedure:
3-Chloropropanesulfonyl chloride (4.58 mL, 37.7 mmol) was added dropwise to a solution of 4-[7-(benzyloxy)-2-(ethoxymethyl)-1H-imidazo[4,5-c]quinolin-1-yl]butan-1-amine dihydrochloride (12.1 g, 25.3 mmol) and triethylamine (14.0 mL, 101 mmol) in dichloromethane (168 mL) at room temperature. The solution was stirred for 17 hours, then transferred to a separatory funnel and washed with 5% aqueous sodium carbonate, water, and saturated aqueous sodium chloride. The organic layer was dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was dissolved in DMF (168 mL) and treated with 1,8-diazabicyclo[5.4.0]undec-7-ene (5.70 mL, 38 mmol). The solution was stirred for 40 hours, then the DMF was removed under reduced pressure. The residue was dissolved in dichloromethane and washed repeatedly with water then saturated aqueous sodium carbonate. The organic layer was dried over anhydrous sodium sulfate, filtered, and evaporated to afford 7-(benzyloxy)-1-[4-(1,1-dioxidoisothiazolidin-2-yl)butyl]-2-(ethoxymethyl)-1H-imidazo[4,5-c]quinoline in almost quantitative yield with some residual 1,8-diazabicyclo[5.4.0]undec-7-ene as a brown oil, which was used without further purification.
Reaction SMILES: [Br:1][C:2]1([Br:10])[CH2:4][C:3]1([CH3:9])[C:5]([O:7]C)=[O:6].[OH-].[Li+].Cl>O1CCCC1.O>[Br:1][C:2]1([Br:10])[CH2:4][C:3]1([CH3:9])[C:5]([OH:7])=[O:6]
Reactant: COC(=O)C1(C)CC1(Br)Br
Agent: Cl
Agent: [Li+]
Agent: [OH-]
Solvent: C1CCOC1
Solvent: O
Product: CC1(C(=O)O)CC1(Br)Br
Reaction time: 8 h
Yield: 620.4 %

Procedure:
To 25 mL of a 50:50 mixture of tetrahydrofuran/water was added 2,2-dibromo-1-methylcyclopropanecarboxylic acid, methyl ester(2.72 g, 10 mmol)and lithium hydroxide (0.8 g, 20 mmol). The reaction mixture was stirred overnight. The reaction mixture was acidified with 1 M hydrochloric acid (24 mL). The reaction mixture was extracted with dichloromethane (2×25 mL) and the organic phases were collected, washed with brine, dried (MgSO4)and evaporated to give the title product (16 g) as white crystals mp 108-109° C.
Reaction SMILES: [CH:1]1[C:11]2[C:10]3[CH:12]=[CH:13][CH:14]=[CH:15][C:9]=3[CH2:8][N:7]([C:16](=[NH:20])[O:17][CH2:18][CH3:19])[CH2:6][C:5]=2[CH:4]=[CH:3][CH:2]=1.Cl[C:22]([O:24][CH2:25][CH2:26][CH2:27][CH3:28])=[O:23]>>[CH2:25]([O:24][C:22]([N:20]=[C:16]([N:7]1[CH2:6][C:5]2[CH:4]=[CH:3][CH:2]=[CH:1][C:11]=2[C:10]2[CH:12]=[CH:13][CH:14]=[CH:15][C:9]=2[CH2:8]1)[O:17][CH2:18][CH3:19])=[O:23])[CH2:26][CH2:27][CH3:28]
Reactant: CCOC(=N)N1Cc2ccccc2-c2ccccc2C1
Reactant: CCCCOC(=O)Cl
Product: CCCCOC(=O)N=C(OCC)N1Cc2ccccc2-c2ccccc2C1

Procedure:
starting from ethyl 5,7-dihydro-6H-dibenz[c,e]azepine-6-carboximidate and butyl chloroformate, there is obtained ethyl N-butoxycarbonyl-5,7-dihydro-6H-dibenz[c,e]azepine-6-carboximidate as a syrup, mass spectrum m/e: M+ 366 (6), 337 (10), 293 (12), 263 (67), 194 (100);
Reaction SMILES: C[O:2][C:3]1[CH2:8][CH:7]=[C:6]([C:9]([OH:12])([CH3:11])[CH3:10])[CH2:5][CH:4]=1.[CH3:13][C:14]([C:22]1[CH:23]=[C:24](O)[CH:25]=[C:26]([CH:28]=1)[OH:27])([CH3:21])[CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH3:20].B(F)(F)F.CCOCC.Cl>C1C=CC=CC=1>[OH:27][C:26]1[C:25]2[C@H:5]3[CH2:4][C:3](=[O:2])[CH2:8][CH2:7][C@H:6]3[C:9]([CH3:11])([CH3:10])[O:12][C:24]=2[CH:23]=[C:22]([C:14]([CH3:13])([CH3:21])[CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH3:20])[CH:28]=1
Reactant: COC1=CCC(C(C)(C)O)=CC1
Reactant: CCCCCCC(C)(C)c1cc(O)cc(O)c1
Agent: Cl
Agent: FB(F)F
Solvent: c1ccccc1
Solvent: CCOCC
Product: CCCCCCC(C)(C)c1cc(O)c2c(c1)OC(C)(C)[C@@H]1CCC(=O)C[C@H]21
Temperature: 24 °C
Reaction time: 5 h

Procedure:
A solution of 504 mg. of 1-methoxy-4-(1-hydroxy-1-methylethyl)-1,4-cyclohexadiene and 708 mg. of 5-(1,1-dimethylheptyl)resorcinol in 25 ml. of benzene was stirred at 24° C. while 5 ml. of boron trifluoride diethyl etherate was added in one portion. The reaction mixture was stirred at 24° C. for five hours. The reaction mixture then was added to 20 ml. of 6N hydrochloric acid solution. After allowing the benzene solvent to evaporated from the aqueous acid solution, the solution was extracted several times with diethyl ether. The ethereal extracts were combined, washed with water and with aqueous sodium bicarbonate solution, and dried. Evaporation of the solvent under reduced pressure provided an oil, which was crystallized from hexane to afford dl-cis-1-hydroxy-3-(1,1-dimethylheptyl)-6,6-dimethyl-6,6a,7,8,10,10a-hexahydro-9H-dibenzo[b,d]pyran-9-one.
Reaction SMILES: [CH3:1][C:2]1[CH:3]=[CH:4][CH:5]=[C:6]2[C:14]=1[NH:13][C:12]1[CH2:11][CH2:10][CH2:9][C:8](=[O:15])[C:7]2=1.CCCCC.[H-].[Na+].[F:23][C:24]1[CH:31]=[CH:30][C:27]([CH2:28]Br)=[CH:26][CH:25]=1>CN(C=O)C>[F:23][C:24]1[CH:31]=[CH:30][C:27]([CH2:28][N:13]2[C:12]3[CH2:11][CH2:10][CH2:9][C:8](=[O:15])[C:7]=3[C:6]3[C:14]2=[C:2]([CH3:1])[CH:3]=[CH:4][CH:5]=3)=[CH:26][CH:25]=1
Reactant: Cc1cccc2c3c([nH]c12)CCCC3=O
Reactant: Fc1ccc(CBr)cc1
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: CCCCC
Product: Cc1cccc2c3c(n(Cc4ccc(F)cc4)c12)CCCC3=O
Reaction time: 0.5 h
Yield: 33.6 %

Procedure:
8-Methyl-1,2,3,9-tetrahydro-4H-carbazol-4-one (0.1967 g, 0.99 mmol) is added to a slurry of pentane-washed NaH (0.0449 g, 0.0011 mol) in DMF (2 mL). After stirring for 30 min, p-fluorobenzyl bromide (0.15 mL, 0.0012 mol) is added. Starting material is still present after 3 h, so additional p-fluorobenzyl bromide (0.015 mL, 0.12 mmol) is added and the mixture is stirred overnight. The mixture is then partitioned between aq. sodium bicarbonate and ethyl acetate and the organic layer is dried over sodium sulfate and concentrated to dryness. The resulting solids are chromatographed on silica gel (75 mL) using methanol/dichloromethane (2/98). The impure fractions are rechromatographed on silica gel (60 mL) using methanol/dichloromethane (2/98). The pure fractions are combined and recrystallized from ethyl acetate/hexane/dichloromethane to give 0.1021 g (34%) of the title compound; mp 154-155° C.; MS (ESI+) for C20H18FNO m/z 308.2 (M+H)+; IR (drift) 1635, 1602, 1539, 1510, 1462, 1449, 1414, 1226, 1159, 835, 826, 801, 786, 756, 747 cm−1; 1H NMR (CDCl3) δ2.21, 2.51, 2.59, 2.81, 5.55, 6.87, 6.98, 7.17, 8.23. Anal. Calcd for C20H18FNO: C, 78.15; H, 5.90; N, 4.56. Found: C, 77.72; H, 5.95; N, 4.64.
Reaction SMILES: [CH:1]1[C:13]2[CH2:12][C:11]3[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=3)[C:5]=2[CH:4]=[CH:3][CH:2]=1.C([Li])CCC.CCCCCC.[C:25]([C:29]1[CH:30]=[C:31]([CH3:55])[C:32](=[C:34]([C:45]2[CH:50]=[CH:49][C:48]([C:51]([CH3:54])([CH3:53])[CH3:52])=[CH:47][CH:46]=2)[C:35]2[CH:40]=[CH:39][C:38]([C:41]([CH3:44])([CH3:43])[CH3:42])=[CH:37][CH:36]=2)[CH:33]=1)([CH3:28])([CH3:27])[CH3:26].O>C(OCC)C>[C:25]([C:29]1[CH:30]=[C:31]([CH3:55])[CH:32]([C:34]([C:1]2[C:13]3[CH2:12][C:11]4[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=4)[C:5]=3[CH:4]=[CH:3][CH:2]=2)([C:45]2[CH:50]=[CH:49][C:48]([C:51]([CH3:54])([CH3:53])[CH3:52])=[CH:47][CH:46]=2)[C:35]2[CH:36]=[CH:37][C:38]([C:41]([CH3:44])([CH3:42])[CH3:43])=[CH:39][CH:40]=2)[CH:33]=1)([CH3:26])([CH3:27])[CH3:28]
Reactant: c1ccc2c(c1)Cc1ccccc1-2
Reactant: CC1=CC(C(C)(C)C)=CC1=C(c1ccc(C(C)(C)C)cc1)c1ccc(C(C)(C)C)cc1
Agent: [Li]CCCC
Solvent: O
Solvent: CCOCC
Solvent: CCCCCC
Product: CC1=CC(C(C)(C)C)=CC1C(c1ccc(C(C)(C)C)cc1)(c1ccc(C(C)(C)C)cc1)c1cccc2c1Cc1ccccc1-2
Temperature: 25 °C

Procedure:
In a 200 ml three-necked flask equipped with a magnetic stirrer chip and three-way cock thoroughly purged with nitrogen, 0.653 g of fluorene (3.93 mmol) was dissolved in 50 ml of dehydrated diethylether in a nitrogen atmosphere. To the solution, 2.7 ml of n-butyl lithium/hexane solution (1.58M: 4.27 mmol) was gradually added dropwise in an ice bath and stirred at room temperature over night. To the solution, a solution prepared by dissolving 2.09 g of 3-tert-butyl-1-methyl-6,6-di(4-tert-butyl-phenyl)fulvene (5.06 mmol) in 100 ml of dehydrated diethyl ether was added and stirred under reflux for 10 days and then stirred at room temperature for 11 days. To the reaction mixture, 30 ml of distilled water was gradually added dropwise in an ice bath, and then diethyl ether was added to separate an organic phase. The organic phase was washed with distilled water and saturated brine. The organic phase was dried with anhydrous magnesium sulfate, thereafter the drying agent was filtered off and the solvent was distilled off from the filtrate under reduced pressure to give a reddish-brown solid. The solid was purified with a column chromatography using 150 g of silica gel (developing solvent: n-hexane) and the developing solvent was distilled off under reduced pressure. The remaining product was re-crystallized using hexane and dried under reduced pressure, and thereby the aimed compound was obtained in an amount of 0.439 g (0.758 mmol) as a pale yellow solid (yield: 19%).
Reaction SMILES: [CH2:1]([CH:3]1[CH:29]=[C:28]([CH3:30])[CH2:27][CH:26]([CH3:31])[CH2:25][CH:24]([O:32][CH3:33])[CH:23]2[O:34][C:19]([OH:38])([CH:20]([CH3:37])[CH2:21][CH:22]2[O:35][CH3:36])[C:18](=[O:39])[C:17](=[O:40])[N:16]2[CH:11]([CH2:12][CH2:13][CH2:14][CH2:15]2)[C:10](=[O:41])[O:9][CH:8]([C:42]([CH3:70])=[CH:43][CH:44]2[CH2:49][CH2:48][CH:47]([O:50][CH2:51][CH:52]=[CH:53][C:54]3[CH:59]=[CH:58][C:57]([O:60][Si](C(C)(C)C)(C)C)=[CH:56][CH:55]=3)[CH:46]([O:68][CH3:69])[CH2:45]2)[CH:7]([CH3:71])[CH:6]([OH:72])[CH2:5][C:4]1=[O:73])[CH3:2].N1C=CC=CC=1.F>O1CCCC1>[CH2:1]([CH:3]1[CH:29]=[C:28]([CH3:30])[CH2:27][CH:26]([CH3:31])[CH2:25][CH:24]([O:32][CH3:33])[CH:23]2[O:34][C:19]([OH:38])([CH:20]([CH3:37])[CH2:21][CH:22]2[O:35][CH3:36])[C:18](=[O:39])[C:17](=[O:40])[N:16]2[CH:11]([CH2:12][CH2:13][CH2:14][CH2:15]2)[C:10](=[O:41])[O:9][CH:8]([C:42]([CH3:70])=[CH:43][CH:44]2[CH2:49][CH2:48][CH:47]([O:50][CH2:51][CH:52]=[CH:53][C:54]3[CH:59]=[CH:58][C:57]([OH:60])=[CH:56][CH:55]=3)[CH:46]([O:68][CH3:69])[CH2:45]2)[CH:7]([CH3:71])[CH:6]([OH:72])[CH2:5][C:4]1=[O:73])[CH3:2]
Reactant: CCC1C=C(C)CC(C)CC(OC)C2OC(O)(C(=O)C(=O)N3CCCCC3C(=O)OC(C(C)=CC3CCC(OCC=Cc4ccc(O[Si](C)(C)C(C)(C)C)cc4)C(OC)C3)C(C)C(O)CC1=O)C(C)CC2OC
Agent: *CC(*)C
Agent: F
Solvent: C1CCOC1
Solvent: c1ccncc1
Product: CCC1C=C(C)CC(C)CC(OC)C2OC(O)(C(=O)C(=O)N3CCCCC3C(=O)OC(C(C)=CC3CCC(OCC=Cc4ccc(O)cc4)C(OC)C3)C(C)C(O)CC1=O)C(C)CC2OC
Temperature: 25 °C
Reaction time: 2 h

Procedure:
To a solution of 17-ethyl-1,14-dihydroxy-12-[2'-(4"-(4'"-t-butyldimethylsiloxycinnamyloxy)-3"-methoxycyclohexyl)-1'-methylvinyl]23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo[22.3.1.04,9 ]octacos-18-ene-2,3,10,16-tetraone (190 mg in 2 ml tetrahydrofuran contained in a polypropylene vial) was added 500 μl of a solution of hydrogen fluoride-pyridine complex (40% in (2:1) tetrahydrofuran:pyridine) and the mixture stirred at room temperature. After 2 hours, the reaction was quenched by the careful addition of saturated sodium bicarbonate and extracted with ethyl acetate. The combined organics were dried over magnesium sulfate, concentrated in vacuo and purified by flash chromatography on silica gel (ethyl acetate:hexane (2:1) to give the title compound (50 mg).
Reaction SMILES: C([O:3][C:4]([C:6]1[C:7]([N:25]2[CH2:29][CH2:28][CH2:27][CH2:26]2)=[N:8][C:9]2[C:14]([C:15]=1[CH2:16][C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=1[Cl:23])=[CH:13][C:12]([Cl:24])=[CH:11][CH:10]=2)=[O:5])C.[OH-].[Na+]>>[Cl:24][C:12]1[CH:13]=[C:14]2[C:9](=[CH:10][CH:11]=1)[N:8]=[C:7]([N:25]1[CH2:26][CH2:27][CH2:28][CH2:29]1)[C:6]([C:4]([OH:5])=[O:3])=[C:15]2[CH2:16][C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=1[Cl:23]
Reactant: CCOC(=O)c1c(N2CCCC2)nc2ccc(Cl)cc2c1Cc1ccccc1Cl
Agent: [Na+]
Agent: [OH-]
Product: O=C(O)c1c(N2CCCC2)nc2ccc(Cl)cc2c1Cc1ccccc1Cl

Procedure:
The title compound was prepared in analogy to example 12 step B from 6-chloro-4-(2-chloro-benzyl)-2-pyrrolidin-1-yl-quinoline-3-carboxylic acid ethyl ester (50 mg, 0.117 mmol) and 1N NaOH. Pale yellow solid (13 mg, 28%). LC-MS (ESI): 401 (M+H)+.
Reaction SMILES: C([Si]([O:8]/[C:9](/[C:14]1[CH:19]=[CH:18][CH:17]=[C:16]([Cl:20])[CH:15]=1)=[CH:10]\[CH2:11][CH2:12][CH3:13])(C)C)(C)(C)C.CC[C@@H]1[C@@H]2C[C@H]([C@@H](OC3C4C(=CC=CC=4)C(O[C@@H](C4C=CN=C5C=4C=C(OC)C=C5)[C@@H]4N5C[C@H](CC)[C@@H](CC5)C4)=NN=3)C3C=CN=C4C=3C=C([O:42]C)C=C4)N(CC2)C1.CS(N)(=O)=O>C(O)(C)(C)C.O>[Cl:20][C:16]1[CH:15]=[C:14]([C:9](=[O:8])[C@H:10]([OH:42])[CH2:11][CH2:12][CH3:13])[CH:19]=[CH:18][CH:17]=1
Reactant: CCC/C=C(\O[Si](C)(C)C(C)(C)C)c1cccc(Cl)c1
Reactant: CC[C@H]1CN2CC[C@H]1C[C@@H]2[C@@H](Oc1nnc(O[C@@H](c2ccnc3ccc(OC)cc23)[C@H]2C[C@@H]3CCN2C[C@@H]3CC)c2ccccc12)c1ccnc2ccc(OC)cc12
Agent: CS(N)(=O)=O
Solvent: CC(C)(C)O
Solvent: O
Product: CCC[C@@H](O)C(=O)c1cccc(Cl)c1
Yield: 86.8 %

Procedure:
Compound 10k was synthesized by a procedure similar to that described for (R)-10a using (Z)-tert-butyl(1-(3-chlorophenyl)pent-1-enyloxy)dimethylsilane (9k, 4.1 g, 0.013 mol), AD-mix-β (18.5 g), and CH3SO2NH2 (1.3 g, 0.014 mol) in tert-butyl alcohol-water (50 mL:50 mL). The reaction was quenched with sodium sulfite (13.2 g). After purification, 2.4 g (77%) of the desired product was isolated: [α]20D +33.3° (c 1.1, CHCl3); 1H NMR (CDCl3) δ 7.91-7.87 (m, 1H), 7.80-7.75 (m, 1H), 7.63-7.17 (m, 1H), 7.45 (t, 1H, J=7.6 Hz), 5.08-5.00 (m, 1H), 3.58 (d, 1H, J=6.5 Hz), 1.89-1.75 (m, 1H), 1.61-1.35 (m, 3H), 0.93 (t, 3H, J=7.2 Hz); 13C NMR (CDCl3) δ 201.1, 135.4, 133.8, 130.2, 128.6, 126.5, 73.2, 37.8, 18.2, 13.8. C11H13ClO2.
Reaction SMILES: [F:1][CH2:2][CH:3]([O:6][C:7]1[CH:8]=[C:9]([CH:19]=[C:20]([OH:22])[CH:21]=1)[C:10]([NH:12][C:13]1[CH:17]=[CH:16][N:15]([CH3:18])[N:14]=1)=[O:11])[CH2:4][F:5].Cl[C:24]1[N:25]=[CH:26][C:27]([C:30]([O:32][CH3:33])=[O:31])=[N:28][CH:29]=1.C(=O)([O-])[O-].[K+].[K+]>C(#N)C>[F:5][CH2:4][CH:3]([O:6][C:7]1[CH:21]=[C:20]([O:22][C:24]2[N:25]=[CH:26][C:27]([C:30]([O:32][CH3:33])=[O:31])=[N:28][CH:29]=2)[CH:19]=[C:9]([C:10]([NH:12][C:13]2[CH:17]=[CH:16][N:15]([CH3:18])[N:14]=2)=[O:11])[CH:8]=1)[CH2:2][F:1]
Reactant: COC(=O)c1cnc(Cl)cn1
Reactant: Cn1ccc(NC(=O)c2cc(O)cc(OC(CF)CF)c2)n1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC#N
Product: COC(=O)c1cnc(Oc2cc(OC(CF)CF)cc(C(=O)Nc3ccn(C)n3)c2)cn1
Temperature: 120 °C
Reaction time: 3 h
Yield: 90.8 %

Procedure:
A mixture of 3-{[2-fluoro-1-(fluoromethyl)ethyl]oxy}-5-hydroxy-N-(1-methyl-1H-pyrazol-3-yl)benzamide (250 mg, 0.8 mmol), methyl 5-chloropyrazine-2-carboxylate (208 mg, 1.20 mmol) and potassium carbonate (222 mg, 1.61 mmol) in acetonitrile (5 mL) was stirred in a ‘Biotage initiator Microwave’ at 120° C. for 3 hours. The solvent was removed in vacuo and the residue dissolved in ethyl acetate (50 mL) and water (50 mL), the organic layer washed with brine (50 mL), dried (MgSO4), filtered and the solvent removed in vacuo to give a yellow oil which was chromatographed on silica, eluting with 0-100% ethyl acetate in isohexane, to give the desired compound (0.325 g). 1H NMR δ (CDCl3): 3.71 (s, 3H), 3.96 (s, 3H), 4.56 (m, 2H), 4.68 (m, 3H), 6.73 (s, 1H), 6.95 (s, 1H), 7.22 (s, 1H), 7.27 (s, 1H), 7.36 (s, 1H), 8.46 (s, 1H), 8.67 (s, 1H), 8.67 (s, 1H); m/z 448 (M+H)+
Reaction SMILES: [NH2:1][C:2]1[CH:9]=[CH:8][CH:7]=[CH:6][C:3]=1[C:4]#[N:5].O=[C:11]([C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1)[CH2:12][C:13]([O:15][CH2:16][CH3:17])=[O:14]>>[NH2:5][C:4]1[C:3]2[C:2](=[CH:9][CH:8]=[CH:7][CH:6]=2)[N:1]=[C:11]([C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)[C:12]=1[C:13]([O:15][CH2:16][CH3:17])=[O:14]
Reactant: N#Cc1ccccc1N
Reactant: CCOC(=O)CC(=O)c1ccccc1
Product: CCOC(=O)c1c(-c2ccccc2)nc2ccccc2c1N

Procedure:
Prepared as in Example 2a from 2-aminobenzonitrile and ethyl 3-oxo-3-phenylpropanoate as a yellow solid (45%). 1H NMR (400 MHz, DMSO-d6) δ 0.72 (t, J=8.0 Hz, 3H), 3.92 (q, J=8.0 Hz, 2H), 7.44 (m, 5H), 7.50 (m, 1H), 7.61 (bs, 2H), 7.73 (m, 1H), 7.83 (d, J=8.0 Hz, 1H), 8.37 (d, J=8.0 Hz, 1H). MS 293 (MH+).
Reaction SMILES: [C:1]1([C:7]#[C:8][C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[Cl:15][SiH:16]([CH:18]([SiH:22]([Cl:24])[Cl:23])[SiH:19]([Cl:21])[Cl:20])[Cl:17]>C1C=CC=CC=1>[Cl:15][Si:16]1([Cl:17])[CH:7]([C:1]2[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=2)[CH:8]([C:9]2[CH:10]=[CH:11][CH:12]=[CH:13][CH:14]=2)[Si:19]([Cl:21])([Cl:20])[CH:18]1[SiH:22]([Cl:24])[Cl:23]
Reactant: C(#Cc1ccccc1)c1ccccc1
Reactant: Cl[SiH](Cl)C([SiH](Cl)Cl)[SiH](Cl)Cl
Solvent: c1ccccc1
Product: Cl[SiH](Cl)C1[Si](Cl)(Cl)C(c2ccccc2)C(c2ccccc2)[Si]1(Cl)Cl
Reaction time: 5 h
Yield: 12.3 %

Procedure:
Hydrosilation of diphenylacetylene with tris(dichlorosilyl)methane in the presence of H2PtCl6 /IPA. Into the same apparatus as described in Example 1 were place 3.39 g of diphenylacetylene, 5.91 g of tris(dichlorosilyl)methane, 40 ml of dried benzene, and 100 μl of a 0.1 M H2PtCl6 /IPA solution to form a mixture. The mixture was stirred for 5 hours at reflux temperature and then the solvent removed at atmospheric pressure. The residue was vacuum distilled at 67 Pa to yield a mixture comprising 7.51 g of 1,1,3,3-tetrachloro-2-dichlorosilyl-4,5-diphenyl-1,3-disilacyclopentane (TCD-GC area of 12.3%) and 1,1,3,3 -tetrachloro-2-(1,2-dichloro-2,3-diphenyl- 1 -sila-2-propenyl)-4,5-diphenyl-1,3-disilacyclopentane (TCD-GC area 74%). 1,1,3,3-Tetrachloro-2-dichlorosilyl4,5-diphenyl-1,3-disilacyclopentane=1H-NMR (CDCl3, ppm): 1.72 (d, 3.4 Hz, 1H, SiCHSi), 3.47-3.53 (m, 2H, CHPh), 5.8 (d, 3.5 Hz, 1H, SiH), 7.15-7.28 (m, 10 H, ArH). 1,1,3,3-Tetrachloro-2-(1,2-dichloro-2,3-diphenyl-1 -sila-2-propenyl)-4,5-diphenyl-1,3-disilacyclopentane=1H-NMR (CDC13, ppm): 1.73(s, 1H, SiCHSi), 3.52-3.55 (m, 2H, CHPh), 7.12-7.50 (m, 21H, C=CHPh and ArH).
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]2[CH:12]([C:13]3[CH:18]=[CH:17][C:16]([Cl:19])=[CH:15][CH:14]=3)[NH:11][C:10]([C:20]3[CH:25]=[CH:24][C:23]([C:26]([CH3:35])([CH3:34])[C:27]([N:29]([CH2:32][CH3:33])[CH2:30][CH3:31])=[O:28])=[CH:22][C:21]=3[O:36][CH2:37][CH3:38])=[N:9]2)=[CH:4][CH:3]=1.[C:39](Cl)([Cl:41])=[O:40]>>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C@H:8]2[C@@H:12]([C:13]3[CH:14]=[CH:15][C:16]([Cl:19])=[CH:17][CH:18]=3)[N:11]([C:39]([Cl:41])=[O:40])[C:10]([C:20]3[CH:25]=[CH:24][C:23]([C:26]([C:27](=[O:28])[N:29]([CH2:32][CH3:33])[CH2:30][CH3:31])([CH3:35])[CH3:34])=[CH:22][C:21]=3[O:36][CH2:37][CH3:38])=[N:9]2)=[CH:4][CH:3]=1
Reactant: O=C(Cl)Cl
Reactant: CCOc1cc(C(C)(C)C(=O)N(CC)CC)ccc1C1=NC(c2ccc(Cl)cc2)C(c2ccc(Cl)cc2)N1
Product: CCOc1cc(C(C)(C)C(=O)N(CC)CC)ccc1C1=N[C@@H](c2ccc(Cl)cc2)[C@@H](c2ccc(Cl)cc2)N1C(=O)Cl
Yield: 55.9 %

Procedure:
2-{4-[4,5-Bis-(4-chloro-phenyl)-4,5-dihydro-1H-imidazol-2-yl]-3-ethoxy-phenyl}-N,N-diethyl-isobutyramide (90 mg, 0.163 mmol) was reacted with phosgene (101 uL, 0.196 mmol, 20% solution in toluene) using the procedure as described in example 12 to give cis-4,5-bis-(4-chloro-phenyl)-2-[4-(1-diethylcarbamoyl-1-methyl-ethyl)-2-ethoxy-phenyl]-4,5-dihydro-imidazole-1-carbonyl chloride (56 mg, 56% yield) as white solids.
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([Mg]Br)=[CH:4][CH:3]=1.Cl[Si:11]1([CH2:16][Cl:17])[CH2:15][CH2:14][CH2:13][CH2:12]1>>[Cl:17][CH2:16][Si:11]1([C:5]2[CH:6]=[CH:7][C:2]([F:1])=[CH:3][CH:4]=2)[CH2:15][CH2:14][CH2:13][CH2:12]1
Reactant: Fc1ccc([Mg]Br)cc1
Reactant: ClC[Si]1(Cl)CCCC1
Product: Fc1ccc([Si]2(CCl)CCCC2)cc1

Procedure:
In the same apparatus and procedures as Example 1 was reacted 62 ml of 4-fluorophenylmagnesiumbromide solution (1.0 M in diethylether) with 1-chloro-1-chloromethyl-1-silacyclopentane prepared from the above procedure i) for 1 hr at 60° C. In the same method as Example 1 was treated the reaction product to give 10.34 g of 1-chloromethyl-1-(4-fluorophenyl)-1-silacyclopentane (b.p. 98° C./0.5 mmHg).
Reaction SMILES: B(Br)(Br)Br.[Cl:5][C:6]1([Cl:18])[CH2:8][C:7]1([C:10]1[CH:15]=[CH:14][C:13]([O:16]C)=[CH:12][CH:11]=1)[CH3:9]>C(Cl)Cl>[Cl:5][C:6]1([Cl:18])[CH2:8][C:7]1([C:10]1[CH:15]=[CH:14][C:13]([OH:16])=[CH:12][CH:11]=1)[CH3:9]
Reactant: COc1ccc(C2(C)CC2(Cl)Cl)cc1
Agent: BrB(Br)Br
Solvent: ClCCl
Product: CC1(c2ccc(O)cc2)CC1(Cl)Cl
Reaction time: 1 h

Procedure:
A solution of 6.1 g. (0.0242 mole) of boron tribromide in 25 ml. of methylene dichloride was added dropwise to a stirred solution of 6.1 g. (0.0264 mole) of p-(2,2-dichloro-1-methylcyclopropyl)anisole in 25 ml. of methylene dichloride cooled in an ice bath. The reaction mixture was stirred at 0° for one hour, then the ice bath was removed and the mixture stirred for an additional one hour. The reaction mixture was quenched in ice water and the layers separated. The aqueous layer was extracted with methylene dichloride, and the combined methylene dichloride solutions were washed with water and with dilute sodium hydroxide solution. At this point the sodium salt of p-(2,2-dichloro-1-methylcyclopropyl)phenol separated and was collected by filtration. The filter cake was combined with the original aqueous layer and acidified with concentrated hydrochloric acid. The acidified solution was extracted with ether and the ether dried over anhydrous sodium sulfate and concentrated in vacuo. The residue was recrystallized from carbon tetrachloride to give p-(2,2-dichloro-1-methylcyclopropyl)phenol, m.p. 125°-126°C.
Reaction SMILES: C(P1(=O)OP(CCC)(=O)OP(CCC)(=O)O1)CC.[NH2:19][C:20]1[N:25]=[C:24]([CH3:26])[C:23]([CH2:27][C:28]2[CH:33]=[CH:32][C:31]([CH2:34][C:35]([OH:37])=[O:36])=[CH:30][CH:29]=2)=[C:22]([NH:38][CH2:39][CH2:40][CH2:41][CH2:42][CH3:43])[N:21]=1.[CH3:44][N:45]([CH3:49])[CH2:46][CH2:47]O>CN(C1C=CN=CC=1)C.CN(C=O)C>[NH2:19][C:20]1[N:25]=[C:24]([CH3:26])[C:23]([CH2:27][C:28]2[CH:29]=[CH:30][C:31]([CH2:34][C:35]([O:37][CH2:47][CH2:46][N:45]([CH3:49])[CH3:44])=[O:36])=[CH:32][CH:33]=2)=[C:22]([NH:38][CH2:39][CH2:40][CH2:41][CH2:42][CH3:43])[N:21]=1
Reactant: CCCCCNc1nc(N)nc(C)c1Cc1ccc(CC(=O)O)cc1
Reactant: CN(C)CCO
Agent: CCCP1(=O)OP(=O)(CCC)OP(=O)(CCC)O1
Agent: CN(C)c1ccncc1
Solvent: CN(C)C=O
Product: CCCCCNc1nc(N)nc(C)c1Cc1ccc(CC(=O)OCCN(C)C)cc1
Temperature: 25 °C
Reaction time: 24 h

Procedure:
A solution of T3P (1.57M in THF, 0.42 ml) was added to a mixture of the product from example 34 step (viii) (0.15 g), N,N-dimethylethanolamine (0.08 ml), TEA (0.3 ml) and DMAP (0.02 g) in DMF (5 ml) and stirred at rt for 24 h. The mixture was partitioned between DCM/water, the organics separated, washed with aq NaHCO3 soln, brine, dried and evaporated under reduced pressure. The residue was purified by RPHPLC, then the product dissolved in MeCN (10 ml) and PS-TBD (0.1 g) added and left for 2 h. The mixture was filtered, the solvent evaporated under reduced pressure and the residue triturated with isohexane and filtered to afford the title compound, 0.034 g.
Reaction SMILES: [NH:1]1[C:9]2[C:4](=[C:5]([O:10][CH2:11][CH2:12][CH2:13]Cl)[CH:6]=[CH:7][CH:8]=2)[CH:3]=[CH:2]1.[OH:15][C:16]1([C:22]2[CH:31]=[CH:30][C:29]3[C:24](=[CH:25][CH:26]=[C:27]([O:32][CH2:33][CH3:34])[CH:28]=3)[CH:23]=2)[CH2:21][CH2:20][NH:19][CH2:18][CH2:17]1>>[NH:1]1[C:9]2[C:4](=[C:5]([O:10][CH2:11][CH2:12][CH2:13][N:19]3[CH2:20][CH2:21][C:16]([OH:15])([C:22]4[CH:31]=[CH:30][C:29]5[C:24](=[CH:25][CH:26]=[C:27]([O:32][CH2:33][CH3:34])[CH:28]=5)[CH:23]=4)[CH2:17][CH2:18]3)[CH:6]=[CH:7][CH:8]=2)[CH:3]=[CH:2]1
Reactant: CCOc1ccc2cc(C3(O)CCNCC3)ccc2c1
Reactant: ClCCCOc1cccc2[nH]ccc12
Product: CCOc1ccc2cc(C3(O)CCN(CCCOc4cccc5[nH]ccc45)CC3)ccc2c1
Yield: 45 %

Procedure:
Beginning with 0.155 gm (0.70 mMol) 1-(4-indolyloxy)-3-chloropropane and 0.155 gm (0.70 mMol) 4-hydroxy-4-(6-ethoxynaphth-2-yl)piperidine, 0.140 gm (43%) of the title compound was recovered as a white solid by the procedure described in Example 1.