Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [C:1]([C:4]1[C:13]2[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=2)[C:7]([C:14]([O:16][CH3:17])=[O:15])=[CH:6][CH:5]=1)(=[O:3])[CH3:2].[F:18][C:19]([F:37])([F:36])[C:20]1[CH:21]=[C:22]([C:30](=O)[C:31]([F:34])([F:33])[F:32])[CH:23]=[C:24]([C:26]([F:29])([F:28])[F:27])[CH:25]=1.[OH-].[Ca+2].[OH-].CN(C)C=O>COC(C)(C)C>[F:18][C:19]([F:36])([F:37])[C:20]1[CH:21]=[C:22]([C:30]([C:31]([F:34])([F:33])[F:32])=[CH:2][C:1]([C:4]2[C:13]3[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=3)[C:7]([C:14]([O:16][CH3:17])=[O:15])=[CH:6][CH:5]=2)=[O:3])[CH:23]=[C:24]([C:26]([F:27])([F:28])[F:29])[CH:25]=1
Reactant: COC(=O)c1ccc(C(C)=O)c2ccccc12
Reactant: O=C(c1cc(C(F)(F)F)cc(C(F)(F)F)c1)C(F)(F)F
Agent: [Ca+2]
Agent: [OH-]
Solvent: COC(C)(C)C
Solvent: CN(C)C=O
Product: COC(=O)c1ccc(C(=O)C=C(c2cc(C(F)(F)F)cc(C(F)(F)F)c2)C(F)(F)F)c2ccccc12
Reaction time: 10 h

Procedure:
A mixture of methyl 4-acetyl-1-naphthalenecarboxylate (5.36 g, 23.5 mmol), 1-[3,5-bis(trifluoromethyl)phenyl]-2,2,2-trifluoroethanone (7.28 g, 23.5 mmol), calcium hydroxide (1.40 g, 18.9 mmol), N,N-dimethylformamide (16 mL) and tert-butyl methyl ether (32 mL) was boiled with provision of the apparatus comprising a ten-plate Oldershaw column and decanter described in Example 1, Step A for removal of the tert-butyl methyl ether/water azeotrope. As the decanter trap contained an amount of tert-butyl methyl ether sufficient to dissolve all of the water formed by the reaction, the condensate in the trap did not separate into layers containing predominately water and predominately tert-butyl methyl ether. Tert-butyl methyl ether was removed by gradually draining the decanter trap until the pot temperature was 85° C. To maintain this temperature, tert-butyl methyl ether was added as needed to compensate for loss of solvent from the apparatus. The total time from beginning heating the reaction mixture to stopping distillation, not including a shutdown period overnight, was about 10 h. During this time period no additional calcium hydroxide was added to the reaction mixture.
Reaction SMILES: [CH3:1][O:2][C:3](=[O:23])[CH2:4][C:5]1[C:6]([Cl:22])=[N:7][C:8]([CH2:14][C:15]2[CH:20]=[CH:19][C:18]([NH2:21])=[CH:17][CH:16]=2)=[N:9][C:10]=1[N:11]([CH3:13])[CH3:12].C1CN([P+](ON2N=NC3C=CC=CC2=3)(N2CCCC2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F.[CH:57]1[C:66]2[C:61](=[CH:62][CH:63]=[CH:64][CH:65]=2)[CH:60]=[CH:59][C:58]=1[C:67](O)=[O:68].O>CN(C=O)C>[Cl:22][C:6]1[C:5]([CH2:4][C:3]([O:2][CH3:1])=[O:23])=[C:10]([N:11]([CH3:12])[CH3:13])[N:9]=[C:8]([CH2:14][C:15]2[CH:16]=[CH:17][C:18]([NH:21][C:67]([C:58]3[CH:59]=[CH:60][C:61]4[C:66](=[CH:65][CH:64]=[CH:63][CH:62]=4)[CH:57]=3)=[O:68])=[CH:19][CH:20]=2)[N:7]=1
Reactant: COC(=O)Cc1c(Cl)nc(Cc2ccc(N)cc2)nc1N(C)C
Reactant: O=C(O)c1ccc2ccccc2c1
Agent: F[P-](F)(F)(F)(F)F
Agent: c1ccc2c(c1)nnn2O[P+](N1CCCC1)(N1CCCC1)N1CCCC1
Solvent: CN(C)C=O
Solvent: O
Product: COC(=O)Cc1c(Cl)nc(Cc2ccc(NC(=O)c3ccc4ccccc4c3)cc2)nc1N(C)C

Procedure:
To a mixture of methyl[2-(4-aminobenzyl)-4-chloro-6-(dimethylamino)pyrimidin-5-yl]acetate (0.090 g, 0.30 mmol) and PyBOP (0.187 g, 0.36 mmol) in anhydrous DMF (1 mL) at room temperature was added 2-naphthoic acid (0.062 g, 0.36 mmol). The resulting reaction mixture was stirred at room temperature for 3 hours at which time water was added and the resulting aqueous phase was extracted with EtOAc. The combined organic extracts was sequentially washed with 0.5N HCl, saturated NaHCO3, and brine, dried over anhydrous MgSO4, filtered, and concentrated in vacuo to give methyl {4-chloro-6-(dimethylamino)-2-[4-(2-naphthoylamino)benzyl]pyrimidin-5-yl}acetate as a colorless oil.
Reaction SMILES: Cl[P:2]1[N:5]([C:6]([CH3:9])([CH3:8])[CH3:7])[P:4](Cl)[N:3]1[C:11]([CH3:14])([CH3:13])[CH3:12].[C:15]([C:19]1[CH:20]=[C:21]([CH:45]=[C:46]([C:49]([CH3:52])([CH3:51])[CH3:50])[C:47]=1[OH:48])[CH2:22][CH2:23][C:24]([O:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][CH2:34][CH2:35][CH2:36][CH2:37][CH2:38][CH2:39][CH2:40][CH2:41][CH2:42][CH2:43][CH3:44])=[O:25])([CH3:18])([CH3:17])[CH3:16]>C(N(CC)CC)C>[C:15]([C:19]1[CH:20]=[C:21]([CH2:22][CH2:23][C:24]([O:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][CH2:34][CH2:35][CH2:36][CH2:37][CH2:38][CH2:39][CH2:40][CH2:41][CH2:42][CH2:43][CH3:44])=[O:25])[CH:45]=[C:46]([C:49]([CH3:51])([CH3:50])[CH3:52])[C:47]=1[O:48][P:2]1[N:5]([C:6]([CH3:9])([CH3:8])[CH3:7])[P:4]([O:48][C:47]2[C:19]([C:15]([CH3:18])([CH3:17])[CH3:16])=[CH:20][C:21]([CH2:22][CH2:23][C:24]([O:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][CH2:34][CH2:35][CH2:36][CH2:37][CH2:38][CH2:39][CH2:40][CH2:41][CH2:42][CH2:43][CH3:44])=[O:25])=[CH:45][C:46]=2[C:49]([CH3:50])([CH3:52])[CH3:51])[N:3]1[C:11]([CH3:14])([CH3:13])[CH3:12])([CH3:16])([CH3:17])[CH3:18]
Reactant: CC(C)(C)N1P(Cl)N(C(C)(C)C)P1Cl
Reactant: CCCCCCCCCCCCCCCCCCOC(=O)CCc1cc(C(C)(C)C)c(O)c(C(C)(C)C)c1
Solvent: CCN(CC)CC
Product: CCCCCCCCCCCCCCCCCCOC(=O)CCc1cc(C(C)(C)C)c(OP2N(C(C)(C)C)P(Oc3c(C(C)(C)C)cc(CCC(=O)OCCCCCCCCCCCCCCCCCC)cc3C(C)(C)C)N2C(C)(C)C)c(C(C)(C)C)c1

Procedure:
The procedure of Example 1 is repeated using 2,4-dichloro-1,3-di-tert-butyl-1,3,2,4-diazadiphosphetidine, n-octadecyl 3,5-di-tert-butyl-4-hydroxyhydrocinnamate and triethylamine to give the title compound.
Reaction SMILES: [S:1]1[CH:5]=[CH:4][N:3]=[C:2]1[CH2:6][NH:7][CH2:8][CH2:9][NH2:10].[CH2:11]([N:13]=[C:14]=[S:15])[CH3:12]>>[CH2:11]([NH:13][C:14]([NH:10][CH2:9][CH2:8][NH:7][CH2:6][C:2]1[S:1][CH:5]=[CH:4][N:3]=1)=[S:15])[CH3:12]
Reactant: CCN=C=S
Reactant: NCCNCc1nccs1
Product: CCNC(=S)NCCNCc1nccs1

Procedure:
Reacting N-(2-thiazolylmethyl)ethylenediamine with ethyl isothiocyanate by the procedure of Example 3(b) and then chromatographing gives N-ethyl-N'-[2-(2-thiazolylmethylamino)ethyl]thiourea. Reacting this thiourea with lead cyanamide by the procedure of Example 3(b) gives N-cyano-N'-ethyl-N"-[2-(2-thiazolylmethylamino)ethyl]-guanidine.
Reaction SMILES: [C:1]1([C:7]2[NH:8][C:9]3[CH:10]=[CH:11][CH:12]=[C:13]4[C:19](=[O:20])[NH:18][CH2:17][CH2:16][C:15]=2[C:14]=34)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[CH:21](C1C=C(B(O)O)C=CC=1)=[O:22]>>[CH:21]([C:5]1[CH:6]=[C:1]([C:7]2[NH:8][C:9]3[CH:10]=[CH:11][CH:12]=[C:13]4[C:19](=[O:20])[NH:18][CH2:17][CH2:16][C:15]=2[C:14]=34)[CH:2]=[CH:3][CH:4]=1)=[O:22]
Reactant: O=C1NCCc2c(-c3ccccc3)[nH]c3cccc1c23
Reactant: O=Cc1cccc(B(O)O)c1
Product: O=Cc1cccc(-c2[nH]c3cccc4c3c2CCNC4=O)c1

Procedure:
In a manner similar to that described above for Compound 12, the tricyclic bromide (381 mg, 1.44 mmol) and 3-formylbenzeneboronic acid (345 mg, 2.16 mmol) were coupled to yield 2-(3-formylphenyl)-3,4,5,6-tetrahydro-1H-azepino[5,4,3-cd]indol-6-one 15, 346 mg (83%), as a tan solid. 1H NMR (300 MHz, d6-DMSO) δ2.86 (m, 2H), 3.16 (m, 2H), 7.01 (t, 1H, J=7.8 Hz), 7.34 (d, 1H, J=7.3 Hz), 7.50 (m, 2H), 7.73 (m, 2H), 7.85 (br t, 1H), 7.94 (s, 1H), 9.88 (s, 1H), 11.50 (brs, 1H).
Reaction SMILES: [C:1]([O:5][C:6]([N:8]1[C@H:14]([C:15](O)=[O:16])[CH2:13][CH2:12][C@@H:11]2[C@H:9]1[CH2:10]2)=[O:7])([CH3:4])([CH3:3])[CH3:2].CO>C1COCC1>[C:1]([O:5][C:6]([N:8]1[C@H:14]([CH2:15][OH:16])[CH2:13][CH2:12][C@@H:11]2[C@H:9]1[CH2:10]2)=[O:7])([CH3:4])([CH3:3])[CH3:2]
Reactant: CC(C)(C)OC(=O)N1[C@@H]2C[C@@H]2CC[C@H]1C(=O)O
Solvent: C1CCOC1
Solvent: CO
Product: CC(C)(C)OC(=O)N1[C@H](CO)CC[C@H]2C[C@H]21
Temperature: 25 °C
Reaction time: 2 h

Procedure:
To a solution of D5 (11 g, 45.6 mmol) in THF (350 mL) cooled at 0° C., BH3 1M in THF (90 mL, 90 mmol) was added and the mixture was stirred at room temperature for 2 hours. Methanol (50 mL) was added; this solution was concentrated and co-evaporated twice from methanol to give the title compound. Yield (11 g, 100%).
Reaction SMILES: C(#N)C.[OH:4][CH2:5][CH2:6][O:7][CH2:8][CH2:9][O:10][C:11](=[O:20])[C:12]1[CH:17]=[CH:16][C:15]([OH:18])=[C:14]([Cl:19])[CH:13]=1.[C:21](Cl)(=[O:25])[C:22]([CH3:24])=[CH2:23]>CN1CCCC1=O>[C:21]([O:4][CH2:5][CH2:6][O:7][CH2:8][CH2:9][O:10][C:11](=[O:20])[C:12]1[CH:17]=[CH:16][C:15]([OH:18])=[C:14]([Cl:19])[CH:13]=1)(=[O:25])[C:22]([CH3:24])=[CH2:23]
Reactant: O=C(OCCOCCO)c1ccc(O)c(Cl)c1
Reactant: C=C(C)C(=O)Cl
Solvent: CN1CCCC1=O
Solvent: CC#N
Product: C=C(C)C(=O)OCCOCCOC(=O)c1ccc(O)c(Cl)c1

Procedure:
A 500-ml eggplant type flask was charged with 50 g of 3-chloro-4-hydroxybenzoic acid methyl ester, 285 g of diethyleneglycol and further with 2.5 g of PTS (p-toluenesulfonic acid monohydrate) as a catalyst to form a mixture. The mixture was heated with stirring on an oil bath, externally regulated at a temperature of 150° C., to react the mixture for 5 hours. Thereafter, excess diethylene glycol therein was removed by means of vacuum distillation. The residue therein was poured into ice water and the precipitated crystals were recrystallized using benzene/ethanol to obtain 49 g of 3-chloro-4-hydroxybenzoic acid [2-(2-hydroxyethoxy)ethyl]-ester (melting point: 77.5° to 78° C.). To 100 ml of an acetonitrile solution containing 30 g of the 3-chloro-4-hydroxybenzoic acid [2-(2-hydroxyethoxy)ethyl]ester, 57.2 g of N-methylpyrrolidone and further 36 g of methacrylic acid chloride were added with stirring to form a solution. The solution was stirred for 8 hours at 40° C. to react the solution. Thereafter, excess methacrylic acid chloride was removed by means of vacuum distillation. The reaction mixture remaining therein was poured into ice water, and the precipitated crystals were obtained by filtration. The crystals were recrystallized with ethyl acetate/n-hexane to obtain 3-chloro-4-hydroxybenzoic acid [2-(2-methacryloyloxyethoxy)ethyl]ester (melting point: 57° to 58.5° C.).
Reaction SMILES: Cl[CH2:2][C:3]([NH:5][C:6]1[CH:7]=[CH:8][C:9]2[C:15]3[S:16][C:17]([C:19]([N:21]([C:23]4[CH:28]=[CH:27][CH:26]=[CH:25][C:24]=4[Cl:29])[CH3:22])=[O:20])=[CH:18][C:14]=3[CH2:13][CH2:12][O:11][C:10]=2[CH:30]=1)=[O:4].[CH2:31]([NH:33][CH2:34][CH3:35])[CH3:32]>>[Cl:29][C:24]1[CH:25]=[CH:26][CH:27]=[CH:28][C:23]=1[N:21]([CH3:22])[C:19]([C:17]1[S:16][C:15]2[C:9]3[CH:8]=[CH:7][C:6]([NH:5][C:3](=[O:4])[CH2:2][N:33]([CH2:34][CH3:35])[CH2:31][CH3:32])=[CH:30][C:10]=3[O:11][CH2:12][CH2:13][C:14]=2[CH:18]=1)=[O:20]
Reactant: CN(C(=O)c1cc2c(s1)-c1ccc(NC(=O)CCl)cc1OCC2)c1ccccc1Cl
Reactant: CCNCC
Product: CCN(CC)CC(=O)Nc1ccc2c(c1)OCCc1cc(C(=O)N(C)c3ccccc3Cl)sc1-2

Procedure:
Following the procedure in Example 147 for 237, 8-(2-chloroacetamido)-N-(2-chlorophenyl)-N-methyl-4,5-dihydro-benzo[b]thieno[2,3-d]oxepine-2-carboxamide and diethyl amine were reacted to give 169. MS: (ESI+) 498.2
Reaction SMILES: Br[C:2]1[CH:3]=[CH:4][C:5]2[C:9]([C:10]3[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=3)=[C:8]([C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=3)[O:7][C:6]=2[CH:22]=1.C([Li])CCC.[B:28](OC)([O:31]C)[O:29]C.Cl>CCCCCC.C1COCC1>[C:16]1([C:8]2[O:7][C:6]3[CH:22]=[C:2]([B:28]([OH:31])[OH:29])[CH:3]=[CH:4][C:5]=3[C:9]=2[C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1
Reactant: Brc1ccc2c(-c3ccccc3)c(-c3ccccc3)oc2c1
Reactant: COB(OC)OC
Agent: Cl
Agent: [Li]CCCC
Solvent: CCCCCC
Solvent: C1CCOC1
Product: OB(O)c1ccc2c(-c3ccccc3)c(-c3ccccc3)oc2c1
Temperature: -40 °C
Yield: 60 %

Procedure:
Under an argon atmosphere, 400 mL of anhydrous THF were added to 40.2 g of 6-bromo-2,3-diphenylbenzo[b]furan, and the mixture was stirred at −40° C. During the stirring, 72 mL of a 1.6-M solution of n-butyllithium in hexane were added to the mixture. The reaction solution was stirred for 1 hour while being heated to 0° C. The reaction solution was cooled to −78° C. again, and a solution of 54.0 g (250 mmol) of trimethyl borate in 50 mL of dry THF was dropped to the solution. The reaction solution was stirred at room temperature for 5 hours. 200 mL of 1N hydrochloric acid were added to the reaction solution, and the mixture was stirred for 1 hour. After that, the water layer was removed. The organic layer was dried with magnesium sulfate, and the solvent was removed by distillation under reduced pressure. The resultant solid was washed with toluene, whereby 21.7 g of 2,3-diphenylbenzo[b]furan-6-boronic acid were obtained (60% yield).
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[C:6]2[NH:8][C:9](=[O:41])[C:10]3([CH:15]([C:16]4[CH:21]=[C:20]([Cl:22])[CH:19]=[CH:18][C:17]=4[O:23][C:24]([C:27]([O:29]C)=[O:28])([CH3:26])[CH3:25])[CH2:14][C:13](=[O:31])[NH:12][CH:11]3[C:32]3[CH:37]=[C:36]([CH3:38])[CH:35]=[CH:34][C:33]=3[O:39][CH3:40])[C:5]2=[CH:4][CH:3]=1.[OH-].[Na+].O>CO>[Cl:1][C:2]1[CH:7]=[C:6]2[NH:8][C:9](=[O:41])[C:10]3([CH:15]([C:16]4[CH:21]=[C:20]([Cl:22])[CH:19]=[CH:18][C:17]=4[O:23][C:24]([C:27]([OH:29])=[O:28])([CH3:25])[CH3:26])[CH2:14][C:13](=[O:31])[NH:12][CH:11]3[C:32]3[CH:37]=[C:36]([CH3:38])[CH:35]=[CH:34][C:33]=3[O:39][CH3:40])[C:5]2=[CH:4][CH:3]=1
Reactant: COC(=O)C(C)(C)Oc1ccc(Cl)cc1C1CC(=O)NC(c2cc(C)ccc2OC)C12C(=O)Nc1cc(Cl)ccc12
Agent: [Na+]
Agent: [OH-]
Solvent: CO
Solvent: O
Product: COc1ccc(C)cc1C1NC(=O)CC(c2cc(Cl)ccc2OC(C)(C)C(=O)O)C12C(=O)Nc1cc(Cl)ccc12
Temperature: 70 °C
Yield: 21.6 %

Procedure:
A mixture of racemic (2′S,3S,4′R)-6-chloro-4′-[5-chloro-2-(1-methoxycarbonyl-1-methyl-ethoxy)-phenyl]-2′-(5-methyl-2-methoxy-phenyl)spiro[3H-indole-3,3′-piperidine]-2,6′(1H)-dione (100 mg, 0.167 mmol), NaOH (33.5 mg, 0.837 mmol), H2O (2 mL) and methanol (3 mL) was heated at 70° C. for 1 h. Then methanol was removed by vacuum and the aqueous solution was acidified to “pH” 1-2 by addition of concentrated HCl aqueous solution. The precipitate was collected by filtration and washed with CH2Cl2 twice to give the title compound as a white solid (21 mg).
Reaction SMILES: [C:1]([O:6][CH2:7][CH3:8])(=[O:5])[CH:2]([CH3:4])[CH3:3].C[Si]([N-][Si](C)(C)C)(C)C.[Li+].Br[CH2:20][C:21]1[CH:26]=[CH:25][C:24]([F:27])=[CH:23][CH:22]=1>O1CCCC1>[CH2:7]([O:6][C:1](=[O:5])[C:2]([CH3:4])([CH3:3])[CH2:20][C:21]1[CH:26]=[CH:25][C:24]([F:27])=[CH:23][CH:22]=1)[CH3:8]
Reactant: CCOC(=O)C(C)C
Reactant: Fc1ccc(CBr)cc1
Agent: C[Si](C)(C)[N-][Si](C)(C)C
Agent: [Li+]
Solvent: C1CCOC1
Product: CCOC(=O)C(C)(C)Cc1ccc(F)cc1
Temperature: -78 °C
Reaction time: 0.75 h

Procedure:
A solution of ethyl isobutyrate (11.03 g, 95 mmol) in tetrahydrofuran (75 mL) was added dropwise to a mixture of a solution of lithium bis(trimethylsilyl)amide in tetrahydrofuran (1.0 M, 100 mL, 100 mmol) and tetrahydrofuran (100 mL) at −78° C. over 15 minutes. The resulting solution was stirred at −78° C. for 45 minutes, and then treated with a solution of 1-bromomethyl-4-fluorobenzene (11.5 mL, 92 mmol) in tetrahydrofuran (25 mL) over 5 minutes. The cooling bath was removed, and the reaction mixture was stirred for 18 hours at room temperature. 1.0 N aqueous hydrochloric acid was added, and the layers were separated. The aqueous phase was extracted with ethyl acetate, and the combined organic phases were washed with 1.0 N aqueous hydrochloric acid, dried over sodium sulfate, and concentrated under vacuum to provide a brown liquid (20.7 g, quantitative) used without further purification. 1H NMR (300 MHz, CDCl3) δ7.07 (m, 2H), 6.94 (t, J=9 Hz, 2H), 4.10 (q, J=7 Hz, 2H), 2.82 (s, 2H), 1.23 (t, J=7 Hz, 3H), 1.16 (s, 6H).
Reaction SMILES: [Si:1]([N:8]([CH2:12][C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1)[CH2:9][CH:10]=[CH2:11])([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].[CH3:19][SiH:20]([O:24][CH2:25][CH3:26])[O:21][CH2:22][CH3:23]>[Pt].C([Si](C)(C)O[Si](C=C)(C)C)=C.C1(C)C=CC=CC=1>[Si:1]([N:8]([CH2:12][C:13]1[CH:14]=[CH:15][CH:16]=[CH:17][CH:18]=1)[CH2:9][CH2:10][CH2:11][Si:20]([CH3:19])([O:24][CH2:25][CH3:26])[O:21][CH2:22][CH3:23])([C:4]([CH3:7])([CH3:5])[CH3:6])([CH3:3])[CH3:2]
Reactant: CCO[SiH](C)OCC
Reactant: C=CCN(Cc1ccccc1)[Si](C)(C)C(C)(C)C
Agent: [Pt]
Agent: C=C[Si](C)(C)O[Si](C)(C)C=C
Solvent: Cc1ccccc1
Product: CCO[Si](C)(CCCN(Cc1ccccc1)[Si](C)(C)C(C)(C)C)OCC
Temperature: 50 °C
Reaction time: 1 h

Procedure:
A flask equipped with a stirrer, reflux condenser, dropping funnel and thermometer was charged with 26.2 g (0.1 mol) of N-t-butyldimethylsilyl-N-benzyl-N-allylamine and 0.07 g of a toluene solution of platinum/1,3-divinyl-1,1,3,3-tetramethyldisiloxane complex (Pt concentration 3 wt %) and heated at 50° C. Once the internal temperature became steady, 13.4 g (0.1 mol) of methyldiethoxysilane was added dropwise over 1 hour. Stirring was continued at the temperature for a further 1 hour. The reaction solution was distilled, collecting 31.0 g of a fraction having a boiling point of 169-170° C./0.4 kPa.
Reaction SMILES: [C:1]([S:4][CH:5]1[NH:8][C:7](=[O:9])[CH2:6]1)(=[O:3])[CH3:2].O.[C:11]([O:15][CH2:16][CH:17]=[CH2:18])(=[O:14])[CH:12]=[O:13]>C1C=CC=CC=1>[CH2:16]([O:15][C:11]([CH:12]([OH:13])[N:8]1[CH:5]([S:4][C:1](=[O:3])[CH3:2])[CH2:6][C:7]1=[O:9])=[O:14])[CH:17]=[CH2:18]
Reactant: C=CCOC(=O)C=O
Reactant: CC(=O)SC1CC(=O)N1
Solvent: O
Solvent: c1ccccc1
Product: C=CCOC(=O)C(O)N1C(=O)CC1SC(C)=O

Procedure:
4-Acetylthioazetidin-2-one (Annalen, 1974, p. 553) (1.4 g) and allyl glyoxylate hydrate (1.5 g) are refluxed for 2 hours in benzene to afford a solution of 1-(allyloxycarbonylhydroxymethyl)-4-acetylthioazetidin-2-one which is cooled and used directly in the next step.
Reaction SMILES: I[C:2]1[CH:9]=[C:8]([O:10][CH3:11])[C:7]([O:12][CH3:13])=[CH:6][C:3]=1[CH:4]=O.CCN(CCOC1C=CC(CC2C=CC=CC=2)=CC=1)CC.Cl.C(#N)C.[C:39]([O:43][CH3:44])(=[O:42])[CH:40]=[CH2:41]>[Zn].O>[CH3:13][O:12][C:7]1[CH:6]=[C:3]2[C:2](=[CH:9][C:8]=1[O:10][CH3:11])[CH2:41][C:40]([C:39]([O:43][CH3:44])=[O:42])=[CH:4]2
Reactant: COc1cc(I)c(C=O)cc1OC
Reactant: C=CC(=O)OC
Agent: CCN(CC)CCOc1ccc(Cc2ccccc2)cc1
Agent: Cl
Agent: [Zn]
Solvent: O
Solvent: CC#N
Product: COC(=O)C1=Cc2cc(OC)c(OC)cc2C1
Temperature: 80 °C
Yield: 21.3 %

Procedure:
2-Iodo-4,5-dimethoxybenzaldehyde (292 mg, 1.0 mmol), CoCl2 (dppe) complex (26.4 mg, 0.05 mmol), dppe (19.9 mg, 0.05 mmol) and zinc power (179.8 mg, 2.75 mmol) were placed in a vial, which was sealed with a septum and flushed several times with nitrogen. Acetonitrile (3 mL) and methyl acrylate (172 mg, 2.0 mmol) were then sequentially added and the mixture was heated at 80° C. overnight. Water was then added and the mixture was extracted with ethyl acetate. The organic extracts were concentrated under reduced pressure and the residue was purified by flash chromatography using petroleum ether/ethyl acetate 8:1 (v:v) as eluent to give methyl 5,6-dimethoxy-1H-indene-2-carboxylate (50 mg, 21%). LC-MS (ES-API); rt 7.89 min; m/z calculated for C13H14O4 [M+H]+ 235.1, found 235.1.
Reaction SMILES: C[O-].[Na+].CO.[Br:6][C:7]1[S:11][C:10]([C:12](=O)[CH2:13][O:14][C:15]2[C:24]([I:25])=[CH:23][C:22]3[C:21]([CH3:27])([CH3:26])[CH2:20][CH2:19][C:18]([CH3:29])([CH3:28])[C:17]=3[CH:16]=2)=[CH:9][CH:8]=1.[Br-].[CH3:32]P(C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>C1COCC1>[Br:6][C:7]1[S:11][C:10]([C:12]([CH2:13][O:14][C:15]2[C:24]([I:25])=[CH:23][C:22]3[C:21]([CH3:27])([CH3:26])[CH2:20][CH2:19][C:18]([CH3:28])([CH3:29])[C:17]=3[CH:16]=2)=[CH2:32])=[CH:9][CH:8]=1
Reactant: C[PH](c1ccccc1)(c1ccccc1)c1ccccc1
Reactant: CC1(C)CCC(C)(C)c2cc(OCC(=O)c3ccc(Br)s3)c(I)cc21
Agent: C[O-]
Agent: [Br-]
Agent: [Na+]
Solvent: C1CCOC1
Solvent: CO
Product: C=C(COc1cc2c(cc1I)C(C)(C)CCC2(C)C)c1ccc(Br)s1
Temperature: 25 °C
Reaction time: 12 h

Procedure:
A solution of 30% sodium methoxide in methanol (1.65 ml, 8.66 mmol) was added over 8 hours to a mixture of 5-bromo-2-[(3-iodo-5,5,8,8-tetramethyl-5,6,7,8-tetrahydronaphthalen-2-yloxy)acetyl]thiophene (4.3 g, 7.9 mmol) and methyltriphenylphosphine bromide (3.8 g, 10.7 mmol) in THF (45 ml). The mixture was stirred for 12 h at room temperature. The mixture was concentrated in a rotary evaporator under vacuum at 40° C. It was extracted with ethyl ether and washed with water. The organic phase was then dried over magnesium sulfate and concentrated in a rotary evaporator under vacuum at 40° C.
Reaction SMILES: N([N:3]1[C:8]2[CH:9]=[CH:10][CH:11]=[CH:12][C:7]=2[S:6][CH2:5][CH2:4]1)=O.C([O-])(O)=O.[Na+].[C:18](O)(=O)[CH3:19]>[Zn]>[CH3:4][N:3]1[CH2:19][CH2:18][C:12]2[N:3]3[CH2:4][CH2:5][S:6][C:7]4[CH:12]=[CH:11][CH:10]=[C:9]([C:8]3=4)[C:7]=2[CH2:8]1
Reactant: CC(=O)O
Reactant: O=NN1CCSc2ccccc21
Agent: O=C([O-])O
Agent: [Na+]
Agent: [Zn]
Product: CN1CCc2c(c3cccc4c3n2CCS4)C1
Temperature: 95 °C

Procedure:
4-Nitroso-3,4-dihydro-2H-benzo[1,4]thiazine (1 g, 5.55 mmol) was dissolved in acetic acid (25 mL) and N-Me- piperidone (753 mg, 6.66 mmol) and zinc dust (1.8 g, 27.77 mmol) was added portionwise at RT. The reaction mixture was heated at 95° C. for 2 h. After completion of reaction, the mixture was basified with NaHCO3 and extracted with EtOAc, dried over sodium sulfate and concentrated under vacuum to obtain product. 1H NMR (CD3OD, Formate Salt): d (ppm): 7.20 (d, 1H), 6.98 (t, 1H), 6.90 (d, 1H), 4.32 (t, 2H), 4.28 (s, 2H), 3.50 (t, 2H), 3.30 (m, 2H), 3.10 (t, 2H), 2.98 (s, 3H).
Reaction SMILES: Cl[C:2]1[C:7]([C:8]#[N:9])=[CH:6][CH:5]=[CH:4][N:3]=1.C([Sn](CCCC)(CCCC)[C:15]1[S:16][CH:17]=[CH:18][N:19]=1)CCC>>[S:16]1[CH:17]=[CH:18][N:19]=[C:15]1[C:2]1[N:3]=[CH:4][CH:5]=[CH:6][C:7]=1[C:8]#[N:9]
Reactant: N#Cc1cccnc1Cl
Reactant: CCCC[Sn](CCCC)(CCCC)c1nccs1
Product: N#Cc1cccnc1-c1nccs1
Yield: 39 %

Procedure:
Prepared in 39% yield from 2-chloro-3-cyanopyridine and 2-(tributylstannyl)thiazole according to the procedure described for Example 164A. MS (ESI+) m/z 187.9 (M+H)+; 1H NMR (CDCl3) δ 7.44 (dd, J=7.8, 4.7 Hz, 1H), 7.57 (d, J=3.0 Hz, 1H), 8.10-8.14 (m, 2H), 8.80 (d, J=3.4 Hz, 1H).
Reaction SMILES: [CH2:1]([C:6]1[CH:11]=[CH:10][C:9]([C:12]2[CH:17]=[CH:16][C:15]([C:18]#N)=[CH:14][CH:13]=2)=[CH:8][CH:7]=1)[CH2:2][CH2:3][CH2:4][CH3:5].[H-].C([Al+]CC(C)C)C(C)C.S(=O)(=O)(O)[OH:31].O>C1(C)C=CC=CC=1>[CH2:1]([C:6]1[CH:11]=[CH:10][C:9]([C:12]2[CH:17]=[CH:16][C:15]([CH:18]=[O:31])=[CH:14][CH:13]=2)=[CH:8][CH:7]=1)[CH2:2][CH2:3][CH2:4][CH3:5]
Reactant: O=S(=O)(O)O
Reactant: CCCCCc1ccc(-c2ccc(C#N)cc2)cc1
Agent: CC(C)C[Al+]CC(C)C
Agent: [H-]
Solvent: Cc1ccccc1
Solvent: O
Product: CCCCCc1ccc(-c2ccc(C=O)cc2)cc1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
A solution of 10 g of 4-pentyl-4'-cyanobiphenyl in 150 ml of toluene was treated dropwise at 0° C. with 65 ml of a 1M solution of diisobutylaluminium hydride in toluene while gassing with nitrogen. The reaction mixture was stirred at room temperature overnight, then treated dropwise with 340 ml of 1N sulphuric acid, stirred at room temperature for 1 hour, poured into 1,000 ml of water and then extracted three times with 100 ml of ethyl acetate each time. The combined organic phases were washed twice with 50 ml of saturated sodium chloride solution each time, dried over magnesium sulphate, filtered and subsequently concentrated. Chromatographic purification of the residue on silica gel with hexane/ethyl acetate (vol. 9:1) gave 10.1 g of 4-pentyl-4'-biphenylcarboxaldehyde.
Reaction SMILES: [CH3:1][C:2]1[CH:3]([OH:7])[CH2:4][CH2:5][CH:6]=1.N1C=CN=C1.[C:13]([Si:17](Cl)([C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1)[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1)([CH3:16])([CH3:15])[CH3:14].O>CN(C)C1C=CN=CC=1.ClCCl>[C:13]([Si:17]([O:7][CH:3]1[CH2:4][CH2:5][CH:6]=[C:2]1[CH3:1])([C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1)[C:18]1[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=1)([CH3:16])([CH3:14])[CH3:15]
Reactant: CC(C)(C)[Si](Cl)(c1ccccc1)c1ccccc1
Reactant: CC1=CCCC1O
Agent: CN(C)c1ccncc1
Agent: c1c[nH]cn1
Solvent: ClCCl
Solvent: O
Product: CC1=CCCC1O[Si](c1ccccc1)(c1ccccc1)C(C)(C)C
Temperature: 25 °C
Reaction time: 16 h
Yield: 32 %

Procedure:
To a solution of 2-methylcyclopent-2-en-1-ol (23.06 g, 235.0 mmol), 1H-imidazole (32.0 g, 470 mmol) and N,N-dimethyl-4-pyridinamine (5.74 g, 47.0 mmol) in dichloromethane (470 mL) at room temperature is added tert-butylchlorodiphenylsilane (90.41 g, 328.94 mmol) over 15 min. After stirring the reaction mixture at room temperature for 16 h, water (300 mL) is added and the layers are separated. The aqueous layer is extracted with dichloromethane (2×200 mL). The combined organic portions are dried over sodium sulfate, filtered, and concentrated to give the crude product (108 g) as a colorless oil. The crude product is purified in 20 g batches on 330 g silica gel using 0-20% dichloromethane/hexane (product observed on TLC using KMnO4 staining) to give the title compound as a colorless oil (25.3 g, 32%). 1H-NMR (400 MHz, CDCl3) δ 7.72-7.69 (m, 4H), 7.44-7.41 (m, 6H), 5.44-5.41 (m, 1H), 4.72-4.70 (m, 1H), 2.33-2.29 (m, 1H), 2.06-2.01 (m, 2H), 1.74-1.69 (m, 1H), 1.66-1.65 (m, 3H), 1.09 (s, 9H).